Genes are fundamental units of life and their origin has fascinated researchers since the beginning of the molecular era. Many of the studies on the formation of new genes in genomes have focused on gene duplication and subsequent divergence of the two gene copies. But, in recent years, we have learnt that genes can also arise de novo from previously non-genic sequences. The discovery of de novo genes has become possible by the sequencing of complete genomes and the comparison of gene sets between closely related species. Here we wish to test a novel hypothesis, we propose that de novo gene formation dynamics in populations results in substantial differences in gene content between individuals. If they exist, these differences would be not be visible by the current methods to study gene variation, which are based on the comparison of the sequences of each individual to a common set of reference genes. To test our hypothesis, we will need to develop novel computational approaches to first obtain an accurate representation of all transcripts and translated open reading frames in each individual, and then integrate the information at the population level. We propose to apply these methods to two very distinct biological systems, a large collection of Saccharomyces cerevisiae world isolates and a human lymphoblastoid cell line (LCL) panel. For this, we will collect and generate RNA (RNA-Seq) and ribosome profiling (Ribo-Seq) sequencing data. In order to identify de novo originated events occurred within populations, as opposed to phylogenetically conserved genes that have been lost in some individuals, we will also generate similar data from a set of closely related species in each of the two systems. Combined with genomics data, we will identify the spectrum of mutations associated with de novo gene birth with an unprecedented level of detail and uncover footprints of adaptation linked to the birth of new genes.

Mar Albà – Institut Hospital del Mar d’Investigacions Mèdiques (IMIM)
AdG 2021 – LS8

CONDJUST will create a new research field, Conservation Data Justice, that bridges three distinct areas of enquiry: conservation prioritisation, political ecology and Data Justice. The former uses data which risk marginalising rural peoples. The latter does not yet examine conservation data. Meanwhile political ecologists do not yet consider Data Justice approaches when tackling conservation prioritisation. CONDJUST will interrogate conservation data and models, and explore the epistemic communities producing them, to develop new theories of socially just, data-driven conservation. It will challenge the colonising tendencies of prioritisation work and seek decolonising alternatives. CONDJUST is timely because ambitious new global targets seek to safeguard 30% of the planet for conservation by 2030 (and more afterwards). These plans pose risks for rural people because the data and modelling they use can contain diverse forms of bias, exclusion and omission. These risks will grow as more social media data are used in conservation prioritisation. We need insights from Data Justice to understand these dangers, and how they might be counter-acted. This project has four objectives, each with a corresponding work package. These are: 1. Systematically examine the sources of bias and distortion in conservation data used in global prioritisation work. 2. Use Data Justice thinking in new analyses of biodiversity conservation, and increase our understanding of socially just conservation prioritisation. 3. Critically explore the construction of different epistemic communities in conservation prioritisation, and political ecology, to understand what inhibits and enhances learning between them. 4. Examine how policies responding to prioritisation are shaped by, or resist, the new measures proposed. These work packages will be pursued by an interdisciplinary team led by the PI and composed of three post-doctoral researchers, two PhDs, an administrator and an advisory board.

Dan Brockington – Universitat Autònoma de Barcelona (UAB)
AdG 2021 – SH7

Processions were quintessentially performative acts that infused a sense of identity among the urban community by linking the emblematic topography of the city and creating performative spaces of enhanced ritual activity and distinctive auditory landscapes. The premise of Soundspace is that hermeneutic study of the procession as performance affords insight into the dynamic workings of society and the experience of urban life. It aims to go beyond this to assess the impact of urban ritual on participants and ear-witnesses through analysis of the social and cultural processes that lay behind that experience, and of the perceptual discourses that gave it meaning and significance for all those present. The procession formed a moving intersensory experience that also mobilised the emotions of the urban community: but how did this work in practice in the historical past? How can the historian enter into the performative moment to understand the emotional impact of sound in acoustic space?

The project aims to interrogate the multi-faceted relationship between sound, space and society by scrutinising the interstices between collective experience, social expectations and memory through the prism of historical sound studies, an umbrella term here used to combine a cross-disciplinary approach—urban studies, sensory history and history of the emotions—and DH tools: Virtual Reality, digital cartography and semantic discourse analysis. It will forge a new theoretical framework by combining concepts of acoustic and emotional communities to analyse the social and cultural processes involved in the preparation, performance, reception and impact of the procession and the prevailing discourses that forged the significance of processional expression for the urban community. The main objective is to open up new ways to explore the impact of intangible but key features of processions such as acoustic space, soundscape competence, density of sensory experience and emotional response.  

Tess Knighton – Universitat Autònoma de Barcelona (UAB)
AdG 2021 – SH5

My research project proposes studying the origin of state capacity, democracy and political dynasties using the colonial conquest of Latin America as a natural experiment. Much of the recent work on comparative politics and development uses large historical events as fruitful experimentation laboratories. However, the colonial experience looks more similar to a “bundle treatment” than a single treatment. It is difficult to disentangle the role of differences in legal origin from the influences of human capital, etc. To try to overcome this problem, past empirical approaches use a variety of methods like case studies, panel data, country-fixed effects, and instrumental variables. I will try to move one step further in this debate by considering the initial years of the Spanish colonization of Latin America as a natural experiment. My methodological approach has four advantages. First, since I only analyse the initial years of colonization, my empirical strategy is based on the fact that the initial conquerors had no knowledge of the land that they intended to conquer. The second advantage is that, in working with the colonization of Latin America, we only have one colonial power, Spain, which avoids the traditional problems of diversity of legal origins. The third advantage is that the contracts (“Capitulaciones”), that the conquerors signed with the King before embarking to America, and before even knowing anything about the land that he would conquer, and other documents from the Archivo de Indias, provide very rich details on the rules that governed the early institutions (power to tax and rule, the use of military power, the treatment of indigenous groups, etc.). Finally, these documents contain information to locate the initial settlements at the subnational level. The colonization of the Americas and the information contained in the “Capitulaciones” found in the Archivo de Indias provides a unique opportunity to advance the debate on these crucial questions.

Marta Reynal-Querol – Universitat Pompeu Fabra (UPF)
AdG 2021 – SH1

With the advent of Big Data, information is facing new, potentially more damaging, security threats. The current trend to enhance data protection is to use increasingly complex mathematical algorithms to encrypt information. This approach requires exponentially growing amounts of data, time and power resources. REMINDS proposes a radically new concept to boost data security: to act directly at material level, i.e., in the way information is stored. The project is built on the disruptive idea of using voltage to activate/deactivate magnetism via strain or ion migration effects and it tackles novel strategies to control the mutual interactions between ferromagnetic (FM), antiferromagnetic (AFM) and ferroelectric (FE) materials. While data written in ferromagnets can be read using conventional heads, AFM and FE materials are ‘invisible’ to magnetic sensors due to their lack of magnetic stray fields (methods to read sub-200 nm AFM or FE domains are complex and often destructive). REMINDS will develop advanced engineering protocols to (i) transfer information from FM to AFM or FE materials, (ii) keep the data ‘hidden’ in the AFM or FE layers while the FM state is switched off and (iii) retrieve the information whenever deemed necessary. Neuromorphic-inspired layouts will be used to selectively apply these protocols to specific memory units that will incorporate stochastic physical phenomena. This will be the basis of new energy-efficient proof-of-concept data protection designs whose working principle will be tested at lab scale for potential applications in anti-counterfeiting and anti-hacking technologies. REMINDS is expected to revolutionize magnetoelectricity, exploiting voltage-programmable magnetism to an unprecedented extent and forging an entirely new paradigm in data security. Its outcomes will bring ground-breaking scientific contributions to the fields of magnetism, spintronics, piezotronics and flexible electronics, and will have a huge socio-economic impact.

Jordi Sort – Universitat Autònoma de Barcelona (UAB)
AdG 2021 – PE11

The conversion of sunlight photons to electrons is the essence of the natural photosynthesis that powers life. Dedicated antennas funnel the sun’s energy towards reaction centres. Amazingly, nature reaches almost perfect photon-to-electron conversion efficiency, while it regulates down at high light level for protection and survival. How does nature dynamically re-organize the membrane architecture, its packing, order, diffusion, on light stress? Which pathways are taken to charge separation? What is the role of fluctuations, coherences, color and vibrations? My group recently succeeded in first detection of the fs spectral progression of a single exciton, the nanoscale tracking of electron transport and reveal energy disorder of a single photosynthetic complex. These pioneering results, together with our expertise in fs pulse control and nanoimaging, set the grounds to now address photosynthetic light-to-charge transfer in real nanospace and ultrafast. Specific objectives are: Energy transport on the nanoscale: tracking spatiotemporal membrane transport by super-resolved transient optical microscopy and nanophotonic light localization: to reveal disorder and quantify diffusion. Light to charge: photo-current detection of the energy flow: by ultrafast photo-thermoelectric graphene and photo-electrochemical detection I will probe charge separation of the reaction center directly, quantify rate and efficiency. Multidimensional spectra on the nanoscale: by collinear 2D spectroscopic imaging with photocurrent and fluorescence detection, I will map the development of the energy landscape, at special membrane spots, ultimately on a single complex. Functional imaging: visualize the dynamic light-response of the membrane architecture, the changes in packing density, (dis)order, diffusion and pathways to charge separation. The novel tool-set of FastTrack and the insights on nature’s energy strategies are directly relevant for artificial photosynthesis and solar technology.

Niek van Hulst – Institut de Ciències Fotòniques (ICFO)
AdG 2021 – PE4

Focal brain disorders, including stroke, trauma, and epilepsy, are the main causes of disability and loss of productivity in the world, and carry a cumulative cost in Europe of about 500 billion euro/year. Now, physicians diagnose and treat these conditions as if they were caused by local dysfunction due to the pathological process. However, there is growing evidence that, in most neurological and psychiatric disorders, clinical symptoms reflect widespread network abnormalities. Normalization of such network abnormalities through “circuit-based” stimulation would therefore improve function. However, this form of therapy is currently limited by numerous factors: lack of knowledge about the underlying mechanisms and their behavioural relevance; inability to map these abnormalities onto single patients; and, most importantly, a principled understanding of where and how to stimulate the brain to produce functional recovery.

‘NEMESIS’, from Ancient Greek as “give what is due”, aims to “give an injured brain what is missing”, i.e., restore through stimulation normal activity in dysfunctional brain circuitries. By synergizing people, concepts, and technologies, NEMESIS will first characterize the effects of focal injury at multiple spatial and temporal scales (from whole brain to local circuits). Through the combination of observational (e.g., fMRI, EEG, calcium imaging, LFPs) and causal methods (e.g., electro-magnetic stimulation, optogenetics) NEMESIS will test the hypothesis that disconnected networks lie in a “sleep-like state” that impairs communication. Thirdly, NEMESIS will create whole brain models of structure/function to predict the effect of individual lesions and simulate novel stimulation protocols aimed at “re-awakening” the disconnected brain. Finally, proof-of-concept interventions that combine circuit-based stimulation and behavioural training, guided by modelling and animal studies, will be tested to restore normal activity, and so give back what is due.

Gustavo Deco – Universitat Pompeu Fabra (UPF) & Mavi Sánchez – Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
SyG 2022

How can we sustain human well-being within planetary boundaries? What policies and provisioning systems could enable societies to prosper without growth? What politics and alliances are necessary for seeing post[1]growth policies through, and how can the public be engaged in them? What new scientific paradigm could answer such questions? Our societies face multiple intertwined crises. Bold alternatives are sorely needed. This project develops frameworks for ‘Post-Growth Deals’, from empirical research through to practical applications. First, we develop equitable North-South convergence scenarios, modelling human well-being achievement in all countries within planetary boundaries. Second, we articulate post-growth policy packages for the Global North and South, assessing their political acceptability and modelling their effects. Third, we develop models of provisioning systems to ensure future populations have adequate energy, food, shelter, health, and social security. Fourth, we learn from political movements, studying politics and alliances that could bring post[1]growth transitions forward. Fifth, we identify practical steps to bring Post-Growth Deals to life, working with four representative communities to co-produce knowledge and action on the ground. The potential gains of this research are immense: post-growth transitions may unlock a far more ecologically stable and socially prosperous future than current trajectories lead to. REAL brings a paradigm shift moving post-growth science from economics to sustainability studies. We propose a new trans-disciplinary ‘5Ps of post-growth’ science, grounded in resource/energy modelling, political-economy and socio-political analysis – a skill-set that no single researcher or team presently possesses. The PIs are leaders in their fields and bring complementary expertise in: modelling of provisioning systems (JST), political economy and North-South relations (JΗ), and the politics of socio-environmental transformations (GK).

Giorgos Kallis – Universitat Autònoma de Barcelona (UAB)
SyG 2022

Successful defence against invaders is critical for survival of eukaryotic cells. Microbes have developed many strategies to subvert host organisms which, in turn, evolved several innate immune responses to counterattack. As major lipid storage organelles of eukaryotes, lipid droplets (LDs) are an attractive source of nutrients for invaders. Pathogens induce and physically interact with LDs and the current view is that they ‘hijack’ LDs to draw on substrates for host colonisation. We recently challenged this dogma by demonstrating that LDs are endowed with a regulated protein-mediated antibiotic activity. Our work intro-duced the new concept that dependence on host nutrients is a generic ‘Achilles’ heel’ of intracellular pathogens and LDs a chokepoint harnessed by innate immunity to organise a front-line defence. Here, we have formed a multidisciplinary group combining complementary knowledge and transdiscipli-nary expertise to investigate the hypothesis that LDs are innate immunity hubs sensing infection and di-rectly confronting invaders. We will characterise, in cells and animals, how LDs efficiently coordinate and precisely execute a plethora of immune responses such as killing, signalling and inflammation. High-throughput proteomics and lipidomics will identify defensive players. 3D electron tomography and confo-cal microscopy will be combined with proximity labelling strategies and biochemical methods to get un-precedented understanding of host LD-pathogen dynamics. The successful pathogen Mycobacterium tuber-culosis will be used to test the medical significance of our findings and unravel bacterial mechanisms of resistance to LD-mediated defences. Characterisation of these novel innate immune systems will be paradigm-shifting in immunology, physiol-ogy and cell biology. In the age of antimicrobial resistance and viral pandemics, unravelling how eukaryot-ic LDs fight and defeat dangerous microorganisms will inspire new anti-infective therapies.

Albert Pol – Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
SyG 2022

Understanding the establishment of an animal body plan is an important challenge of modern biology. Progress has been mainly limited by (1) a separation of research fields studying genetic and biophysical mechanisms, and (2) a lack of approaches to mimic multicellular tissue organization from first principles. In a cross- disciplinary effort, we will focus on the earliest stages of animal development, when the first steps of cell differentiation define the primary body axis through spatial symmetry breaking, laying the foundation for the future body plan. Our goal is to identify the fundamental mechanisms controlling this symmetry breaking process. To this end, we will study the mechanisms that connect global tissue geometry (shape, size, dimension and physical boundary conditions) with mechano-chemical interactions at the single-cell level. We address the following questions: (i) How do global shape and size control local cellular states and interactions? (ii) How do local cellular states and interactions induce robust symmetry breaking at the tissue level? (iii) To what extent can geometry control cell fate specification in a species-independent manner? To overcome previous limitations, we will establish a comprehensive methodological toolbox of synthetic bottom-up approaches and functional ex vivo assays. We use embryonic stem cells from mouse, zebrafish, and ultimately human as model systems. This will be combined with advanced biophysical techniques and theoretical modeling to systematically dissect the mutual coupling between genetic patterning mechanisms and morphogenetic processes, thereby revealing the multicellular dance underlying tissue symmetry breaking. Our results will shed new light on the long-standing question of how complex biological forms are robustly built from a single fertilized egg, impacting our understanding of organism development and maintenance, and opening new directions for the controlled design of artificial tissues and organs.

Verena Ruprecht – Centre de Regulació Genòmica (CRG)
SyG 2022

Alternative splicing (AS) of mRNA precursors plays important roles in tissue-specific gene regulation and biological regulatory mechanisms, as it can radically alter protein expression, cell phenotypes and physiological responses. Altered splicing also contributes to disease mechanisms, ranging from neurodegeneration to cancer. Drugs modulating AS have recently provided the first therapy for Spinal Muscular Atrophy, a common genetic disorder, illustrating the huge potential for treating many other diseases of unmet need, if only we understood the mechanisms controlling splice site selection and how to regulate them with small molecules.

Unfortunately, despite decades of research, a comprehensive understanding of the mechanisms that control specificity of AS is lacking. This gap in basic knowledge prevents opportunities to harness splicing modulators as tools to study gene function, novel therapeutics, or other biotech applications. This Project addresses head-on the major technical challenges that have limited progress in the AS field. Building on extensive preliminary data, we will use a multidisciplinary approach that combines chemical, structural, cellular, systems biology and machine learning to characterize mechanisms of splice site selection and identify targets for modulating these mechanisms using tool compounds. The outcomes will define key regulatory sequences, splicing factors and molecular interactions involved, thereby illuminating how the splicing machinery efficiently accommodates, yet also discriminates between, a wide range of splice site sequences. This will enable future applications harnessing splice site selection. Our primary goal is to answer the central question, ‘Is it generally possible to modulate splicing with high specificity using small molecules?’ Success will transform our basic understanding of human gene expression and unleash major opportunities for Pharma to develop new therapeutics.

Juan Valcárcel – Centre de Regulació Genòmica (CRG)
SyG 2022

SWIRL – Short-wave Infrared Light emitters based on Colloidal Quantum Dot Technology

Optical sensing and imaging has evolved from taking digital images to a powerful metrology, imaging and data acquisition technique by expanding the spectral coverage from the visible to the short-wave infrared (SWIR). SWIR sensing and imaging is the cornerstone of advanced imaging techniques for 3D visualization, night vision, imaging though adverse weather conditions, biomedical imaging, spectroscopy for food quality and health monitoring, just to name a few. The huge market size of such applications, especially by entering volume markets including consumer electronics and automotive, has led to the first commercial appearances of low cost CMOS compatible SWIR photodetectors and image sensors. Yet for the realization of the afore-mentioned technologies the optical source is an equally important and crucial component to be considered at system level. To date, there is a lack of infrared optical sources that are CMOS compatible, low-cost with competitive performance over the standard costly epitaxial III-V light emitters. Moreover high cost and epitaxial growth manufacturing processes have limited the size and form factor of those sources to small and rigid elements preventing their use as high power and large area illumination sources. SWIRL will undertake this challenge to develop high performance low-cost SWIR optical sources with tunable emission peaks and spectral bandwidths across the eye-safety SWIR window, exploiting colloidal quantum dot technology. By leveraging engineering at the nanoscale and solution processed materials we will develop in TRL4/5 SWIR optical emitters that are low-cost, high efficiency, even rivalling their epitaxial counterparts, and spectrally versatile across the SWIR. We will further demonstrate their use in key applications related to automotive industry as optical sources for active SWIR imaging and in-cabin monitoring in the eye-safety infrared window.

Gerasimos Konstantatos – Institut de Ciències Fotòniques (ICFO)
PoC – 2022

SAFE-ON – Technology for Smart Antimicrobial Coatings

Infectious diseases are a rapidly growing threat to humanity. For instance, the current COVID-19 pandemic, caused by the virus SARS-CoV-2, has already killed over 4.5 million people since 2019 and is taking a devastating socioeconomic toll around the world. Similarly, nosocomial infections are among the major causes of death and increased morbidity, causing thousands of deaths every year in Europe. Recently, the use of antimicrobial coatings has garnered increasing interest as a simple prophylactic strategy to combat these infectious diseases. In this PoC project, we aim advancing a new patented antimicrobial coating technology called SAFE-ON, into the pre-commercial stage, with the aim of demonstrating its breakthrough innovation potential and approaching its arrival to market. The first part of this project encompasses optimization of SAFE-ON technology as highly efficient, smart antimicrobial coatings. This entails the preparation of two antimicrobial coatings based on commercial formulations used in catheters and door-handle covers (one based on hydrogels and the other, on silicone), and subsequent testing of their antimicrobial capacity. It also involves preparing the first two SAFE-ON prototypes: one coated catheter and one door-handle cover. The second part of SAFE-ON will be dedicated to intellectual property (IP) and market aspects needed for the pre-commercialization of this new technology for antimicrobial coatings. This study will include a freedom-to-operate analysis and a market study to identify the antimicrobial coating producers that could ultimately serve as manufacturing partners. In this project we will design, fabricate and evaluate two innovative prototypes incorporating our iodine delivery platform, with the aim to assess the commercial viability of with antimicrobial SAFE-ON coatings, accelerate their market entry and ultimately, commercialize and further develop antimicrobial coatings and other biocide products based on our technology.

Daniel Maspoch – Institut Català de Nanociència i Nanotecnologia (ICN2)
PoC – 2022

FAIRGLUCOSE – Affordable and sustainable self-powered GLUCOSE sensing system for a global FAIR diabetes management

FAIRGLUCOSE proposes a low cost, sustainable and self-powered standalone glucose sensing system that relies on the well-known oxidation process of glucose coming from finger prick blood and transfers it to a voltage readout through an innovative and extremely simple strategy. In this way, a measurement that typically requires a potentiostat with a microcontroller and a battery is performed here with a minimalistic and battery-less circuit that fits within the footprint of a commercial glucose strip. This allows for a reduction not only in device cost, but also in the generation of waste of electrical and electronic equipment (WEEE or e-waste), avoiding the cumulative effect of millions of tests and their corresponding batteries performed at remote sites away from adequate recycling infrastructures. In order to interpret the result, the strip can be integrated in a card format that translates voltage into level bars accounting for low, normal and high glucose indicators – a solution that would substitute urine strips – or into a more sophisticated but still low-cost card containing a NFC chip allowing the transferring of a numeric result into a cell phone. Both cards could be implemented with state-of-the art flexible electronics technologies and could be reused infinite times, as energy would always come from the sample. The first targeted market of FAIRGLUCOSE solutions is located in low and middle-income countries, where cost of current glucometers limits severely the self-monitoring of blood glucose among population. However, at mid-term it is likely that the sustainability and affordability of the approach displaces the current glucose players in some market niches of developed countries and generates new applications in the healthcare and agro-food arena. Thus, FAIRGLUCOSE aims to investigate the commercial feasibility of this disruptive approach and create an innovation roadmap that allows deploying the technology where it can make the most.

Neus Sabaté – Institut de Nicroelectrònica de Barcelona – Centre Nacional de Microelectrònica (CSIC -IMB-CNM)
PoC – 2022

Cytodesign – Novel engineered cytokines for human therapy

Cytokines are biomolecules of great potential interest for human therapy. They modulate the immune system and play an important role in cancer, inflammation, immune response and tissue regeneration. Despite their great potential, there are only a handful of cytokines approved for therapeutic purposes. This is because many of them can have adverse side effects as they usually target different cell types, which adds to their low serum half-life, high production costs, or lack of physiological efficacy. Different methods have been proposed to improve the pharmacodynamics and pharmacokinetics of selected cytokines. However, other properties do also need improvement, such as achieving effective local concentration at the target site; promoting the right activity in cytokines with dual functionality and decreasing toxicity by removing binding to unwanted cell types. To help solving these issues, we have developed a new protein design strategy that can be applied to all helix-bundle cytokines, many of which have been shown to be therapeutically relevant. The resulting products are uniquely modified cytokines with improved properties. Amongst such properties, our products show increase stability, higher affinity and specificity for their target receptors and should have reduced toxicity, all of which translate into greater safety and efficacy. We have initial evidence both (in vitro and in vivo) of the superiority of our designs over conventional cytokines, and in this project we will fully validate our technological platform and advance in the development of a business plan following the advice of several venture capital and pharma companies contacted to date, with the idea of laying the basis for the creation of a new start-up company.

Luis Serrano – Centre de Regulació Genòmica (CRG)
PoC2- 2022

TRANSIONICS – Solid-State Ionics Synaptic Transistors for Neuromorphic Computing

Neuromorphic computing will revolutionize artificial intelligence for applications such as autonomous driving, smart diagnosis or natural-language understanding by emulating the operation of efficient biological neural networks. The main challenge in this field is the substitution of conventional transistors for synaptic transistors able to learn in ways similar to a neural synapse, i.e. the development of multistate non-volatile transistors. However, currently existing synaptic transistors have been developed using electrolytes that are by nature unstable and difficult to integrate such as ionic liquids or proton conducting polymers. TRANSIONICS will deliver highly stable (non-volatile), silicon-compatible and scalable solid state synaptic transistors by exploiting the first-ever room temperature oxide-ionic electrolyte developed in the ERC CoG grant (ULTRASOFC) held by the PI. TRANSIONICS transistors are able to modulate its channel properties with external stimulus like real neurons by reducing/oxidizing a mixed ionic-electronic conductor unveiled at ULTRASOFC. Additionally, TRANSIONICS is compatible with mainstream microelectronics fabrication technology, which makes it ideal for developing high density brain-like computer chips. The goals of the TRANSIONICS project are i) to evaluate the technical feasibility for the fabrication of unique all-solid-oxide synaptic transistors with lateral architecture; ii) to assess the silicon- compatibility and scalability of the TRANSIONICS transistors; iii) to define an IPR strategy for technology transfer; iv) to build a value proposition for a startup company and to identify customer segments with industrial partners. To achieve these goals, the PI has joined around the project team that combines applied research, technology transfer and market uptake expertise.

Albert Tarancón – Institut de Recerca en Energia de Catalunya (IREC)
PoC1 – 2022

AMORE – A distributional MOdel of Reference to Entities

“When I asked my seven-year-old daughter “”Who is the boy in your class who was also new in school last year, like you?””, she instantly replied “”Daniel””, using the descriptive content in my utterance to identify an entity in the real world and refer to it. The ability to use language to refer to reality is crucial for humans, and yet it is very difficult to model. AMORE breaks new ground in Computational Linguistics, Linguistics, and Artificial Intelligence by developing a model of linguistic reference to entities implemented as a computational system that can learn its own representations from data.

This interdisciplinary project builds on two complementary semantic traditions:
1) Formal semantics, a symbolic approach that can delimit and track linguistic referents, but does not adequately match them with the descriptive content of linguistic expressions;
2) Distributional semantics, which can handle descriptive content but does not associate it to individuated referents.

AMORE synthesizes the two approaches into a unified, scalable model of reference that operates with individuated referents and links them to referential expressions characterized by rich descriptive content. The model is a distributed (neural network) version of a formal semantic framework that is furthermore able to integrate perceptual (visual) and linguistic information about entities. We test it extensively in referential tasks that require matching noun phrases (“the Medicine student”, “the white cat”) with entity representations extracted from text and images. AMORE advances our scientific understanding of language and its computational modeling, and contributes to the far-reaching debate between symbolic and distributed approaches to cognition with an integrative proposal. I am in a privileged position to carry out this integration, since I have contributed top research in both distributional and formal semantics. ”

Gemma Boleda – Universitat Pompeu Fabra (UPF)
StG2016 – Social Sciences & Humanitites (SH4)

Aftermath – The aftermath of the East Asian war of 1592-1598

Aftermath seeks to understand the legacy of the East Asian War of 1592-1598. This conflict involved over 500,000 combatants from Japan, China, and Korea; up to 100,000 Korean civilians were abducted to Japan. The war caused momentous demographic upheaval and widespread destruction, but also had long-lasting cultural impact as a result of the removal to Japan of Korean technology and skilled labourers. The conflict and its aftermath bear striking parallels to events in East Asia during World War 2, and memories of the 16th century war remain deeply resonant in the region. However, the war and its immediate aftermath are also significant because they occurred at the juncture of periods often characterized as “medieval” and “early modern” in the East Asian case.

What were the implications for the social, economic, and cultural contours of early modern East Asia?
What can this conflict tell us about war “aftermath” across historical periods and about such periodization itself?

There is little Western scholarship on the war and few studies in any language cross linguistic, disciplinary, and national boundaries to achieve a regional perspective that reflects the interconnected history of East Asia. Aftermath will radically alter our understanding of the region’s history by providing the first analysis of the state of East Asia as a result of the war. The focus will be on the period up to the middle of the 17th century, but not precluding ongoing effects.

The team, with expertise covering Japan, Korea, and China, will investigate three themes: the movement of people and demographic change, the impact on the natural environment, and technological diffusion. The project will be the first large scale investigation to use Japanese, Korean, and Chinese sources to understand the war’s aftermath. It will broaden understandings of the early modern world, and push the boundaries of war legacy studies by exploring the meanings of “aftermath” in the early modern East Asian context.

Rebekah Clements – Universitat Autònoma de Barcelona (UAB)
StG2017 – Social Sciences & Humanitites (SH6)

MIRAGE –Independence and Quality of Mass Media in the Internet Age

The Internet was expected to make citizens considerably more informed and better able to hold politicians and powerful interests accountable. Many predicted it would also effectively complement traditional media and improve news reporting. These expectations have not been met. There is no evidence that citizens have become more informed; they have, however, become more ideologically polarized, possibly due to online media overexposing users to like-minded content.

At the same time, traditional media are struggling: competition from online platforms has slashed advertising revenues forcing newspapers to close or downsize. These changes risk undermining the quality of reporting and making media more vulnerable to capture by special interests. My project examines how the Internet has transformed the way news is produced and disseminated, both directly and through its influence on traditional media, and its ultimate effect on media independence and content quality.

To this end, I tackle three distinct but intertwined questions:

First, I study how lower advertising revenues affect newspapers’ organization and content quality by exploiting the staggered introduction of advertising platform Craigslist across the US.
Second, I examine how media dependence on advertisers influences news bias by testing the relationship between advertising spending by car manufacturers and coverage of car safety recalls in US newspapers.
Finally, I study how the dependence of media on banks affects coverage of financial issues; focusing on Europe’s sovereign debt crisis, I test whether newspapers linked to banks with higher exposure to risky debt endorsed different crisis-management measures. My results will shed light on the deep transformations the media industry is undergoing and their implications for the quality of democracy.

Ruben Durante – Universitat Pompeu Fabra (UPF)
StG2017 – Social Sciences & Humanitites (SH1)

RAINDROPS – Resilience and Adaptation in Drylands. Identifying past water management practices for drought-resistant crops

RAINDROPS will investigate cultivation practices that support human resilience and adaptation in drylands, by developing an innovative and reliable methodology for the identification of water management practices from archaeobotanical remains. Irrigation, river floods or permanent water sources are often deemed necessary for cultivation to be practised in drylands. However, there are modern examples that testify to the existence of successful rain-fed cultivation systems, even in hyper-arid environments.

Quantification of the extent of these practices in the past has the potential to dramatically change our understanding of human adaptation and agriculture. By establishing a protocol for the accurate identification of rain-fed cultivation, RAINDROPS will pave the way for the investigation of this practice in the past. Highly controlled data on phytolith ratios, and carbon, oxygen and silicon isotopes from macro- and micro-remains from experimental fields of finger millet [Eleusine coracana (L.) Gaertn.] and sorghum [Sorghum bicolor (L.) Moench] will be validated with ethnographic evidence before being applied to selected key archaeological case studies. RAINDROPS will advance research in: (a) archaeobotanical methodology; (b) resilience theory; (c) physiology of drought-resistant crops; and (d) TEK of cultivation systems in drylands. This will for the first time allow a thorough evaluation of the relative importance of different water management practices in dryland cultivation in the past, and their significance for human adaptation to arid environments. The experimental work on finger millet and sorghum, at present two of the most important dryland crops, will provide valuable information on cultivation practices and plant physiology that will also inform current research on improvements of drought-resistant species –thereby contributing to work on improving the livelihood for over two billion people currently at risk from arid or changing environmental conditions.

Carla Lancelotti – Universitat Pompeu Fabra (UPF)
StG2017 – Social Sciences & Humanities (SH6)

SUEE – Strategic Uncertainty in Economic Environments

This proposal concerns two sets of projects that tackle theoretical challenges raised by the data broker and online advertisement industry. 1-Strategic Uncertainty (SU) in Economic Environments: By assuming that individuals have correct beliefs about others’ behavior, the equilibrium approach in economics assumes away SU. But SU is central to many settings. Testament to this is the existence of a data broker industry, in which data on agents’ behavior are traded: this information would have no value without SU. Within game theory, non-equilibrium concepts such as rationalizability and models of level-k reasoning have been developed to study SU. But these models have had a limited impact on broader economics. This is partly due to the weakness and limited tractability of these concepts.

Part 1 tackles SU in order to favor a better integration within economics. From a behavioral perspective, I propose axiomatic foundations that justify modeling individuals’ reasoning as stemming from a cost-benefit analysis, and investigate (theoretically and experimentally) how these ideas shed light on the occurrence of equilibrium coordination under SU, i.e. as the result of purely subjective reasoning. From a classical perspective, I develop uniqueness and monotone comparative statics results for non-equilibrium concepts, to favor a better integration of SU in standard economics. Applications include problems of information disclosure of strategic datasets and identification in models of social interactions.

2-Online Auctions with Digital Marketing Agencies (DMA): I study the role of DMA in the auctions used to sell advertisement space on the web. I analyze how collusive bidding can emerge from bid delegation to a common DMA and how this undermines both revenues and efficiency of the auctions used by key players in the industry such as Facebook, Google and Microsoft-Yahoo!. Implications and extensions include business, policy and economics methodology.

Antonio Penta – Universitat Pompeu Fabra (UPF)
StG2017 – Social Sciences & Humanitites (SH1)

EXTREME – The Rise and Fall of Populism and Extremism

In the recent years in advanced democracies there has been a wave of electoral successes of populist politicians supporting extreme messages. Is populism caused by negative economic shocks? If so, what are the mechanisms? What explains heterogeneity in responses to such shocks? In this project, I will test empirically if personal experiences, information environment, and their interaction with aggregate economic shocks shape people’s political decisions.
The project consists of three parts.
First, I will study how personal employment histories, potentially affected by globalization and technological shocks, individual predispositions, and information environment influenced voting for Trump. I will use a unique database of more than 40 million resumes for the period 2010-2016, the largest available repository of resumes of job-seekers in the US, which was not previously used in academic research, and match it with zipcode-level economic and voting variables.
Second, I will study how negative social experiences during the formative years affect subsequent labor market outcomes, antisocial behavior, and the support of populist agenda. I will examine how corporal punishment in schools in UK affected subsequent educational attainment, employment, antisocial behavior, and voting for UKIP and Brexit. I will digitize archival records on regulations and practice of corporal punishment in different educational authorities in the UK during 1970-80s, combining it with contemporary outcomes.
Third, I will examine what makes people actively resist extremist regimes even when it is associated with high personal costs. I will study a historical example of resistance to Nazi regime in Germany during the WWII, which provides unique methodological opportunity to study determinants of resistance to extremism in a high stake environment. I will use a self-collected dataset on treason cases to measure resistance, combining it with data on bombing and exposure to foreign propaganda.

Maria Petrova – Universitat Pompeu Fabra (UPF)
StG2018 – Social Sciences & Humanitites (SH1)

ELECTRON4WATER – Three-dimensional nanoelectrochemical systems based on low-cost reduced graphene oxide: the next generation of water treatment systems

The ever-increasing environmental input of toxic chemicals is rapidly deteriorating the health of our ecosystems and, above all, jeopardizing human health. Overcoming the challenge of water pollution requires novel water treatment technologies that are sustainable, robust and energy efficient. ELECTRON4WATER proposes a pioneering, chemical-free water purification technology: a three-dimensional (3D) nanoelectrochemical system equipped with low-cost reduced graphene oxide (RGO)-based electrodes. Existing research on graphene-based electrodes has been focused on supercapacitor applications and synthesis of defect-free, superconductive graphene. I will, on the contrary, use the defective structure of RGO to induce the production of reactive oxygen species and enhance electrocatalytic degradation of pollutants. I will investigate for the first time the electrolysis reactions at 3D electrochemically polarized RGO-coated material, which offers high catalytic activity and high surface area available for electrolysis. This breakthrough approach in electrochemical reactor design is expected to greatly enhance the current efficiency and achieve complete removal of persistent contaminants and pathogens from water without using any chemicals, just by applying the current. Also, high capacitance of RGO-based material can enable further energy savings and allow using intermittent energy sources such as photovoltaic panels. These features make 3D nanoelectrochemical systems particularly interesting for distributed, small-scale applications.

This project will aim at:
i) designing the optimum RGO-based material for specific treatment goals,
ii) mechanistic understanding of (electro)catalysis and (electro)sorption of persistent pollutants at RGO and electrochemically polarized RGO,
iii) understanding the role of inorganic and organic matrix and recognizing potential process limitations, and
iv) developing tailored, adaptable solutions for the treatment of contaminated water.

Jelena Radjenović – Institut Català de Recerca de l’Aigua (ICRA)
StG2016 – Physical Sciences & Engineering (PE3)

MAPMODERN– Social Networks of the Past: Mapping Hispanic and Lusophone Literary Modernity, 1898-1959

Data mining and big data approaches are changing the ways in which we create knowledge, access information and preserve our cultural heritage. This research applies cutting-edge technology to analyse a neglected aspect of European and non-European social and cultural life of the 20th century: the impact of Hispanic and Lusophone literary networks and cultural mediators in international modernity between 1898 and 1959. The project pursues three central goals: 1) to retrieve the lost history of Iberoamerican mediators in modernist intercultural and multilingual networks and reappraise their role; 2) to narrow the knowledge divide in terms of access and production in the Iberoamerican field by generating and making freely available new and reliable data that addresses the lack of documented cultural heritage, and 3) to offer an innovative and reproducible model that can be applied across periods, languages, and disciplines to analyse cross-border phenomena, under-examined mediators and networks and overshadowed geographical scales in their relations to the wider world. These goals will be achieved by a twofold methodology: i) an open and collaborative research tool providing a data source for quantitative and qualitative analysis on Iberoamerican mediators, and ii) four subprojects on key cultural transformation processes distinctive of modern societies (the institutionalization of Iberoamerican cultures, the rise of translated literature in key Iberoamerican modernist journals, the position of Iberoamerican women in the cultural field, and the role of Iberoamerican mediators in new forms of mass media). By combining computational methods, cultural, literary history, translation, sociology, gender and media studies, I will lead an interdisciplinary team of 6 researchers that will fill the gap in modernist studies and will offer an original, reproducible and empirically tested method for studying social human interaction within a global, cultural and decentred approach

Diana Roig-Sanz –  Universitat Oberta de Catalunya (UOC)
StG2018 – Social Sciences & Humanities (SH5)

EllipticPDE – Regularity and singularities in elliptic PDE’s: beyond monotonicity formulas

One of the oldest and most important questions in PDE theory is that of regularity. A classical example is Hilbert’s XIXth problem (1900), solved by De Giorgi and Nash in 1956. During the second half of the XXth century, the regularity theory for elliptic and parabolic PDE’s experienced a huge development, and many fundamental questions were answered by Caffarelli, Nirenberg, Krylov, Evans, Nadirashvili, Friedman, and many others. Still, there are problems of crucial importance that remain open. The aim of this project is to go significantly beyond the state of the art in some of the most important open questions in this context. In particular, three key objectives of the project are the following. First, to introduce new techniques to obtain fine description of singularities in nonlinear elliptic PDE’s. Aside from its intrinsic interest, a good regularity theory for singular points is likely to provide insightful applications in other contexts. A second aim of the project is to establish generic regularity results for free boundaries and other PDE problems. The development of methods which would allow one to prove generic regularity results may be viewed as one of the greatest challenges not only for free boundary problems, but for PDE problems in general. Finally, the third main objective is to achieve a complete regularity theory for nonlinear elliptic PDE’s that does not rely on monotonicity formulas. These three objectives, while seemingly different, are in fact deeply interrelated.

Xavier Ros-Oton – Universitat de Barcelona (UB)
StG2018 – Physical Sciences & Engineering (PE1)

OPTNETSPACE – Optimal Transport Networks in Spatial Equilibrium

Every year, the world economy invests a large amount of resources to improve or develop transport infrastructure. How should these investments be allocated to maximize social welfare? In this proposal, I propose to develop and apply new methods to study optimal transport networks in general-equilibrium models of international trade, urban economics and economic geography. The methodology will build on recent work (Fajgelbaum and Schaal, 2017), in which my coauthor and I studied the network design problem in a general neoclassical trade framework. In the first project, I develop a new framework to analyze optimal infrastructure investment in an urban setting. The model features people commuting between residential areas and business districts as well as a choice over the mode of transportation. We plan to evaluate the framework to historical data about specific cities. In the second project, I propose and implement an new algorithm to compute optimal transport networks in the presence of increasing returns to transport, a likely prominent feature of real-world networks. The algorithm applies a branch-and-bound method in a series of geometric programming relaxations of the problem. In the third project, I study the dynamic evolution of actual transport networks using satellite data from the US, India and Mexico. In the spirit of Hsieh and Klenow (2007), I use the model to measure distortions in the placement of roads between rich and poor countries. In the fourth project, I study the inefficiencies and welfare losses associated with political economy frictions among governments and planning agencies. I use the model to identify inefficiencies and relate them to measures of institutions and political outcomes. In the final project, I propose a new explanation behind the Zipf’s law distribution of city sizes. I show that Zipf’s law may result from particular topological properties of optimal transport networks that allocate resources efficiently in space.

Edouard Schaal – Centre de Recerca en Economia Internacional (CREI)
StG2018 – Social Scieces & Humanities (SH1)

HYPER-INSIGHT – Hypermutated tumors: insight into genome maintenance and cancer vulnerabilities provided by an extreme burden of somatic mutations

Mutations are the fuel of any evolutionary process, and this also applies to carcinogenesis. The advent of affordable DNA sequencing has enabled mutagenic processes in the human soma to be quantified genome-wide, revealing a striking occurrence of hypermutated tumors. They exhibit an extreme load of somatic changes, often harbouring hundreds of single-nucleotide variants and/or indels per megabase. The HYPER-INSIGHT project is organized into three objectives, which aim to take advantage of the unique opportunity provided by genome sequences of hypermutated and ultramutated tumors. In particular, this work planned in this project aims to further our knowledge on (i) the regional organization of the DNA replication and repair program in human cells, and the determinants thereof, (ii) the extent of selection which acts on somatic variants in various pathways or complexes and (iii) opportunities for selectively targeting DNA repair deficiencies that manifest as hypermutation. Methodologically, our work will employ a three-pronged approach. First, we will perform a multitude of rigorous statistical analyses that draw on the rich and still-expanding resources provided by cancer genomics consortia. Second, we will perform exome and genome sequencing, focusing on ultramutated tumors caused by specific defects in the DNA maintenance machinery. Third, the project involves conditional essentiality screens on cancer cell lines with hypermutant backgrounds. Their goal is to discover synthetic lethality relationships, useful for targeting hypermutating cells, while sparing healthy ones. In summary, one of the promises of cancer genome sequencing projects was to elucidate the mechanisms underlying mutational processes in the human soma, advancing our understanding of this important facet of cancer biology. We will work towards realizing this promise, thereby strengthening the EU’s position in the global scientific endeavour.

Fran Supek – Institut de Recerca Biomèdica (IRB Barcelona)
StG2017 – Life Sciences (LS2)

MiMus – Ioculator seu mimus. Performing Music and Poetry in medieval Iberia

What was the role played by courtly musicians and poets in fostering a performative dimension of cultural life in the late Middle Ages? How did this contribute to the social value of the poet and musician as an artist? In the late medieval period the Crown of Aragon was a political and cultural crossroads, a coveted destination for artists of various kinds who attended the refined court of the Catalan kings. Musicians and performing entertainers with skills in the verbal and non-verbal domains were among the most sought after. This project will review and expand the corpus of documentary evidence informing us about musical activity and performing artists at the court of Aragon in the late medieval period, with the aim to analyse what this tells us about similar activity at other European courts. Thus, it will examine the professional profiles, cultural backgrounds and networks of patronage behind the minstrels who thrived in the Catalan court between 1235 and 1435.

The main source of information will be the Archive of the Crown of Aragon in Barcelona and the Archive of Valencia. The project will also consider the debt of Catalan poetry to foreign musicians, with the aim to establish whether any intertextuality exists between Catalan poetry and the poetry produced in the regions adjacent to the territories of the Crown of Aragon that was specifically mediated by the presence of foreign musicians at the Catalan court.

Specific objectives of the project will be:
1) to establish whether the ideas of minstrelsy passed down to us by literature and scholarship fit the real profiles of minstrels provided by medieval documents;
2) to evaluate the impact, where appropriate, of contacts between religious and ethnic communities in the profession of minstrelsy in late medieval Iberia;
3) to assess the role of queenship in musical and poetic patronage;
4) to clarify the influence of foreign musical traditions on Catalan poetry.

Anna Alberni – Universitat de Barcelona (UB)
CoG2017 – Social Sciences & Humanities (SH5)

Tmol4TRANS – Efficient electronic transport at room temperature by T-shaped molecules in graphene based chemically modified three-terminal nanodevices

Tmol4TRANS aims to create operative molecular systems that will efficiently be inserted in three-terminal nanodevices to function as transistors at room temperature (RT). In the front-line of molecular electronics, the implementation of functional nanodevices in present technologies is mainly hampered by crucial unresolved issues like:
a) reliability of RT experiments on molecular transistors;
b) absence of controlled methodologies to deposit single molecules at specific sites;
c) low conductance values and
d) difficulties in achieving effective three-terminal devices (BJTs/FETs).

Such hindrances involve the nature of the molecules, the absence of controlled deposition methodologies at the nanoscale and the poor stability/contacts between molecules and electrodes. Stable two-terminal nanodevice based on few-layer graphene and containing a Curcuminoid molecule (CCMoid) that I made has shown reasonable molecular conductance at RT, where the CCMoid anchors to the electrodes by pi-pi stacking.

The specific goals of Tmol4TRANS are:
1) to synthesize multifunctional molecules base on “T-shaped” CCMoids and Porphyrin derivatives (PPDs) allowing efficient attachments to electrodes;
2) to fabricate chemically functionalized hybrid graphene transistors;
3) to establish a reliable methodology for positioning the molecules between the electrodes;
4) to investigate the conductance enhancement of the final systems, and
5) to provide the possibility of spin-dependent transport properties by binding such molecules to magnetic metals.

Here, the preparation of nanodevices involves feedback-controlled burning technique for the formation of the few-layer graphene electrodes (source/emitter and drain/collector) and the chemical functionalization of the gate/base, where T-shaped molecules will be fixed by click-chemistry. Tmol4TRANS would have a direct impact in Molecular Electronics and Spintronics, as well as in the broader scope of nanoelectronics.

Núria Aliaga – Institut de Ciència de Materials de Barcelona (CSIC-ICMAB)
CoC2016 – Physical Sciences & Engineering (PE5)

CheSSTaG – Chemotactic Super-Selective Targeting of Gliomas

I propose here a research program aimed to the design a completely new platform for drug delivery. I will combine our existing repertoire of molecular engineering tools based around our established approach to design responsive nanoparticles known as Polymersomes to integrate new features using clinically safe and biodegradable components that will make them super-selective and chemotactic toward glucose gradients so to deliver large therapeutic payload into the central nervous systems and the brain in particular targeting cancer cells harbouring within the healthy. We will do so by engineering components using supramolecular interaction inspired by biological complexity equipping carriers with the ability to self-propelled as a function of glucose gradient. I will complement our proposed design with advanced biological characterisation associating functional information arising form the physiological barrier to structural parameters integrated into the final carrier design.

Giuseppe Battaglia – Institut de Bioenginnyeria de Catalunya (IBEC)
CoC2018 – (PE5) Physical Sciences & Engineering

NEWSPIN – A New Spin on Quantum Atom-Light Interactions

A central goal of quantum optics is to realize efficient, controlled quantum interfaces between atoms and photons. Such interfaces enable broad applications from quantum information processing to quantum nonlinear optics to metrology, and also open a route toward creating exotic quantum states of light and matter. Today, our major paradigm for realizing an efficient interface is based upon the concept of collective enhancement, where using a large number of atoms creates an enhanced coupling to a preferred optical mode over undesired emission into other directions. However, our known error bounds for applications decrease very slowly as a function of system resources, such as the optical depth, thus posing a great challenge for future technologies. In NEWSPIN, we propose a remarkable new way forward, based upon the realization that these conventional error bounds are derived without accounting for multiple scattering and wave interference between emitting atoms. We aim to establish that interference in light emission is in fact a much more powerful resource than the level that we currently exploit it. In particular, beyond the usual collective enhancement, it can simultaneously enable a much stronger collective suppression of emission into undesired directions, and which can yield exponentially better error bounds than was previously known. Underlying this powerful paradigm shift will be the development of a quantum many-body theory of multiple scattering involving photons and atoms, which takes advantage of state-of-the-art tools from condensed matter physics. Beyond robust new routes toward applications, our theory will also reveal exotic new quantum phenomena and lead to new insights into fundamental questions in optics, such as the physical limits to how large the refractive index of an optical material can be. In total, we anticipate that NEWSPIN could greatly enrich our understanding of atom-light interactions and their realm of possibilities.

Darrick Chang – Institut de Ciències Fotòniques (ICFO)
CoC2020 – (PE2) Physical Sciences & Engineering

LArcHer – Breaking barriers between Science and Heritage approaches to Levantine Rock Art through Archaeology, Heritage Science and IT

LArcHer project aims at pioneering a new and more comprehensive way of understanding one of Europe’s most extraordinary bodies of prehistoric art, awarded Unesco World Heritage status in 1998: Levantine rock art (LRA). The ground-breaking nature of the project relies on combining a multidisciplinary (Archaeology, Heritage Science and IT) and multiscale approach (from microanalysis to landscape perspectives) to gain a holistic view of this art. It also aims at closing existing gaps between science and heritage mainstreams, to better understand the values and threats affecting this tradition and bring about a change in the way we understand, care, use and manage this millenary legacy. LArcHer aims are: a) Use cross-disciplinary knowledge and methods to redefine LRA (i.e. new dating techniques to refine chronology, new analytical methods to understand the creative process); b) Use LRA as a proxy to raise new questions of global interest on the evolution of creative thinking and human cognition (i.e. the timing and driving forces behind the birth of anthropocentrism and visual narratives in the history of prehistoric art); c) Develop new research agendas to set off complementary goals between science and heritage and define best practices for open air rock art conservation and management.

Spread across Mediterranean Iberia, LRA is the only European body of figurative art dominated by humans engaged in dynamic narratives of hunting, violence, warfare, dances and so forth. These scenes are unique to explore past social dynamics, human behaviour and cultural practices. As such, it is the only body of European rock art with potential to answer some of the new questions raised by LArcHer.

Key to LArcHer are the systematic recording and analysis of the art through 3D Digital technologies, management and data storage systems, GIS, physicochemical analysis of pigments and bedrock and comparative analysis with other major bodies of art with equivalent developments.

Inés Domingo – Universitat de Barcelona (UB)
CoG 2018 – Social Sciences & Humanities (SH6)

RETVOLUTION – Reticulate evolution: patterns and impacts of non-vertical inheritance in eukaryotic genomes

The traditional view is that species and their genomes evolve only by vertical descent, leading to evolutionary histories that can be represented by bifurcating lineages. However, modern evolutionary thinking recognizes processes of reticulate evolution, such as horizontal gene transfer or hybridization, which involve total or partial merging of genetic material from two diverged species. Today it is widely recognized that such events are rampant in prokaryotes, but a relevant role in eukaryotes has only recently been acknowledged. Unprecedented genomic and phylogenetic information, and recent work from others and us have shown that reticulate evolution in eukaryotes is more common and have more complex outcomes than previously thought. However, we still have a very limited understanding of what are the impacts at the genomic and evolutionary levels.

To address this, I propose to combine innovative computational and experimental approaches. The first goal is to infer patterns of reticulate evolution across the eukaryotic tree, and relate this to current biological knowledge. The second goal is to trace the genomic aftermath of inter-species hybridization at the i) long-term, by analysing available genomes in selected eukaryotic taxa, ii) mid-term, by sequencing lineages of natural fungal hybrids, and iii) short-term, by using re-sequencing and experimental evolution in yeast. A particular focus is placed on elucidating the role of hybridization in the origin of whole genome duplications, and in facilitating the spread of horizontally transferred genes.

Finally results from this and other projects will be integrated into emerging theoretical frameworks. Outcomes of this project will profoundly improve our understanding of reticular processes as drivers of eukaryotic genome evolution, and will impact other key aspects of evolutionary theory, ranging from the concept of orthology to the eukaryotic tree of life.

Toni Gabaldón – Centre de Regulació Genómica (CRG)
CoG2016 – Life Sciences (LS8)

NESTEDMICS – Regulatory and functional architecture of ‘Nested-Sensitivity’ microexon programs

Neural microexons are a paradigmatic example of a cell type-specific transcriptomic program. Microexons are tiny exons that we revealed to have striking neuronal specificity established by their master splicing regulator Srrm4, which activates them during neuronal differentiation. However, our unpublished data challenge this on/off regulatory and functional paradigm. We found that a related paralog, Srrm3, is lowly but significantly expressed also in endocrine pancreas and, together with Srrm4, configure a 3-step switch of Srrm3/4 activity in pancreas (low), brain (mid) and retina (high). These different levels of expression activate increasingly larger subsets of microexons in the three tissues, configuring a triple-nested microexon program. Remarkably, initial results support a model in which microexon subclass inclusion is dictated largely by their sensitivity to Srrm3/4, and each subclass is differentially enriched for distinct functional categories including vesicle-mediated transport, neuronal differentiation and cilium biogenesis. This project will assess the regulatory and functional architecture of this new paradigm by answering: (1) How are the different levels of the master regulators controlled in each cell type? (2) How are the distinct sensitivities of microexons to Srrm3/4 genomically encoded? (3) What are the functional implications of the ‘nestedness’ of the microexon programs? (4) How does misregulation of the nested programs contribute to disease? These goals will be achieved by a combination of high-throughput methods and focused experiments using in vitro and in vivo systems. The expected results will provide a transformative multi-level portrait of microexons, from quantitative regulatory logic to organismal functions. Moreover, this novel paradigm is likely to apply to many other master regulators, expanding the impact of the project and shedding new light into how cell type-specific transcriptomes are established in embryogenesis.

Manuel Irimia – Centre de Regulació Genòmica (CRG)
CoG2020 – Life Sciences (LS2)

HEINSOL – Hierarchically Engineered Inorganic Nanomaterials from the atomic to supra-nanocrystalline level as a novel platform for SOLution Processed SOLar cells

Solution processed inorganic nanocrystal (NC) materials have received enormous attention as an emerging technology to address the TW challenge in solar cells. These nanomaterials offer a unique opportunity for low-cost high efficiency all-inorganic solar cells. Despite the great efforts though, only a limited number of colloidal NC compounds has been successfully employed, which either rely on costly and scarce elements or toxic materials. HEINSOL´s mission is to develop the first highly efficient, robust solution processed solar cell platform based on environmentally friendly, Earth abundant materials.

To achieve this, HEINSOL undertakes a hierarchical approach to tailor the opto-electronic properties of inorganic NCs, starting from the control of composition and their properties at the atomic level and following up with further tailoring their optoelectronic properties via interactions at the supra-nanocrystalline level. HEINSOL, at the atomic level, will develop novel doping schemes for colloidal NCs to tailor their electronic character as well as passivation schemes to reduce the density of unfavourable trap states. At the supra-nanocrystalline level, HEINSOL will explore novel nano-heterojunctions that cater for efficient charge separation and suppressed recombination, elements of paramount importance in high performance solar cells. The microscopic properties of the NCs will be correlated with the macroscopic properties of the NC composites in operating devices, a methodology that will provide new insights on the underlying mechanisms at the nanoscale that govern the properties of those devices. The final goal is to introduce a new architectural platform for solution processed solar cells that will truly expand the material availability for the Photovoltaic Industry.

Gerasimos Konstantatos – Institut de Ciències Fotòniques (ICFO)
CoG2016 – Physical Sciences & Engineering (PE8)

INFRADOT – Mid- and Long-wave infrared Colloidal Quantum Dot Optoelectronics

Optoelectronics – sensing and light emission – in the mid and long-wave infrared (MWIR/LWIR) carry a very large informational dataset of our environment and has created a huge impact on safety and security, quality control, environmental monitoring, imaging, just to name a few sectors. To date, the available optoelectronic materials and technologies developed to serve this very important part of spectrum have been based on high cost and fragmented solutions, curtailing their introduction to a broad market use and unleash of their potential. INFRADOT will address this challenge by developing groundbreaking, lowcost, highly efficient material and device platforms operating in this so far under-exploited part of spectrum. In order to overcome the fundamental constraints arising from the bandgap of available materials, INFRADOT will lead to a paradigm shift in colloidal quantum dot (CQD) technology, by making a leap from – the so far used – interband transitions to intraband transitions. In order to make efficient use of intraband transitions in CQDs, INFRADOT will address several fundamental challenges. It will: i) Make significant advances towards robust heavy doping schemes in CQDs, ii) Explore and control the intraband relaxation pathways by surface and quantum-dot structure engineering at the atomic scale, iii) Shed new insights on charge transport in heavily-doped, electronically coupled CQD films. Capitalizing on these advances and engineering the energetic potential landscape at the nanoscale in heterogeneous CQD and CQD-in-perovskite solids, INFRADOT will create new optoelectronic device architectures to harness efficiently intraband transitions for highly performant, low-cost photodetectors, light emitters and bolometers. The advances made in this project will lead to a new disruptive technology for the MWIR/LWIR, as well as provide extremely important directions in other fields that utilize hot carriers, for catalysis and energy harvesting applications.

Gerasimos Konstantatos – Institut de Ciències Fotòniques (ICFO)
CoG2020 – Physical Sciences & Engineering (PE8)

TOPONANOP – Topological nano-photonics

One of the most fascinating phenomena in nature is the interplay between quantum mechanics and the flow of electrons in solids. A tangible example is the quantum hall effect, where electrons flow with virtually zero dissipation. That is because electrons can flow only in one direction, which makes them move around objects without scattering, representing robustness by topological protection. Essential for this effect is the magnetic field that breaks time-reversal symmetry. Recently, however, with the advent of novel exotic quantum materials, completely new concepts for topological and non-reciprocal phenomena have appeared on the horizon, without the need to apply any magnetic field. These materials exhibit intrinsic topological character due to quantum mechanical interferences.

TOPONANOP’s vision is to exploit these extraordinary quantum properties in order to control light at the nanoscale in a radically new way. One of the main objectives is to generate nanoscale optical fields (plasmons) that propagate in only one direction and implement topologically protected plasmons such that they move around defects and corners. At the same time, visualizing and controlling electromagnetic excitations will be used as a tool to unravel extraordinary phenomena in exotic quantum materials. To this end, TOPONANOP will apply novel low-temperature, THz and infrared, near-field imaging and spectroscopy techniques to directly spatially visualize the plasmon non-reciprocity and topological character. Topological nano-photonics is a new paradigm for novel quantum materials and will enable novel future applications in miniaturized photonic isolators, diodes and logic circuits and could lead to completely new concepts for communication systems, optical transistors and optical information processing.

Frank Koppens – Institut de Ciències Fotòniques (ICFO)
CoG2016 – Physical Sciences & Engineering (PE3)

NONCODRIVERS – Finding noncoding cancer drivers

Finding the mutations, genes and pathways directly involved in cancer is of paramount importance to understand the mechanisms of tumour development and devise therapeutic strategies to overcome the disease. Due to their role in cancer development and maintenance, the proteins encoded by cancer genes are candidate therapeutic targets. Indeed, in recent years we have witnessed the development of successful cancer-targeting therapies to counteract the effect of driver mutations. Although the coding part of the human genome has now largely been explored in the search for cancer driver mutations in most frequent cancer types, the extent of involvement of noncoding mutations in cancer development remains a mystery.

The main challenges faced are:

1) the functional role of most noncoding regions is unknown, and
2) tumours often have thousands of somatic mutations, so that distinguishing cancer driver mutations from bystanders is like finding the proverbial needle in a haystack.

To overcome these two challenges I propose to analyse the pattern of somatic mutations across thousands of tumours in noncoding regions to identify signals of positive selection. These signals are an indication that mutations in the region have been positively selected during tumour evolution and are thus directly involved in the tumour phenotype. The large scale analysis proposed here will allow us to create a catalogue of noncoding elements involved in different types of cancer upon mutations. We will study in detail a selected set of driver elements to uncover their specific function and role in the tumourigenic process. Furthermore, we will explore possibilities of counteracting their driver effect with targeted drugs. The results of this project may boost our understanding of the biological role of noncoding regions, help to unravel novel molecular causes of cancer and provide novel targeted therapeutic opportunities for cancer patients.

Núria López-Bigas – Institut de Recerca Biomèdica (IRB Barcelona)
CoG2015 – Life Sciences (LS2)

ApeGenomeDiversity – Great ape genome variation now and then: current diversity and genomic relics of extinct primates

In our quest to fully understand the processes that shape the genomic variation of species, describing variation of the past is a fundamental objective. However, the origins and the extent of great ape variation, the genomic description of extinct primate species and the genomic footprints of introgression events all remain unknown. Even today, and in contraposition to human evolutionary biology, the almost null presence of ancient great ape samples has precluded a comprehensive exploration of such diversity.

Here, I present two approaches that will expose great ape diversity throughout time and will allow me to compare the genomic impact of introgression events across lineages. First, I would like to take advantage of ancient ape samples that will provide us with a direct view of the genomes of extinct populations. Second, I would like to exploit current and recent diversity to indirectly access the parts of extinct ape genomes that became hybridized with current species in the past. For the latter, we will analyse hundreds of non-invasive samples taken from present-day great apes as well as historical specimens. Altogether, this information will enable me to decipher novel genomes that until now have been lost in time. In this way, I will be able to properly understand the origins and dynamics of genomic variants and to study how admixture has contributed to today´s adaptive landscape.

By completing this proposal and performing analogies to the human lineage, fundamental insights will be revealed about (i) the spatial-temporal history of our closest species and (ii) the functional consequences of introgressed events. On top of that, these results will help to annotate functional consequences of novel mutations in the human genome. In so doing, a fundamental insight will be provided into the evolutionary history of these regions and into human mutations with multiple repercussions in the understanding of evolution and human biology.

Tomàs Marquès – Institut de Biologia Evolutiva – Universitat Pompeu Fabra (IBE-UPF)
CoG2019 – Life Sciences (LS3)

ENGINORG – Engineering kidney organoids to study the interplay between Tissue Mechanics and Metabolism: from development to disease

Research with human pluripotent stem cells (hPSCs) has led to the development of miniorgan-like structures in culture, so called organoids. Generally, organoids are generated exploiting cell-autonomous responses of hPSCs with minimal control over the external inputs supplied to the system. The unrestrained nature of these approaches explains, in part, key shortcomings of the organoid technology, such as limited capacity to recreate all cell types within an organ, maturation and function. Data from my laboratory has shown, for the first time, that the presentation of a physical instruction (elastic modulus-stiffness) during the derivation of hPSCs-kidney progenitor cells results in the generation of hPSCs-kidney organoids with higher differentiation potential and functional attributes. Similarly, our preliminary results show that boosting metabolic activities differentially regulated upon the presentation of controlled physical cues represents a new strategy to generate specific kidney cells on demand. ENGINORG proposes conceptual and technical advances to mechanistically link how the presentation of controlled physical and metabolic constrains during organoid generation are integrated and resolved through gene expression regulation and epigenetics. To this end, we will combine micropatterning techniques, hPSCs-genome engineering, metabolomics, biomaterials design and microfluidics. The identification of the molecular mechanisms connecting how metabolic and mechanical cues modulate cell fate and function will define minimal design principles for the proper control of cell-cell and cell-matrix interplay, and cell organization for organoid generation. This knowledge will be implemented through three interconnected objectives to understand and model early steps of kidney morphogenesis and Congenital anomalies of the kidney and the urinary tract (CAKUT), which account for ~50% of the etiology of chronic kidney disease in children worldwide.

Núria Montserrat Pulido – Institut de Bioenginyeria de Catalunya (IBEC)
CoG2020- Life Sciences (LS9)

PHOTHERM – Photo Thermal Management Materials

Since the beginning of civilization, humanity has built houses to sustain comfortable living conditions throughout the seasons. In our modern society, about 50% of the total energy consumption is used for heating and cooling. Growing demands for thermal management in many different sectors, from electronics to housing, inevitably means increased energy consumption. The primary source of heat is coming from the combustion of fossil, bio, or waste-based feedstocks, all contributing to emissions. This project seeks to fundamentally change how we generate heating and cooling by developing a new class of materials that capture, store, and release both solar and ambient heat. The solar thermal management materials are a unique combination of molecular photo-switches that capture and store sunlight, so-called MOST systems, together with phase change materials (PCM) that can contribute to thermal management. The two classes of materials operate at fundamentally different principles. The input of MOST system is photons, whereas the output is heat. The PCM materials can absorb heat from the environment. By combining the two materials into one, we can harness and upgrade two of the most abundant renewable sources of energy on the planet: ambient heat and sunlight. The materials function will be demonstrated in heat to power devices that can operate 24/7 without the need for traditional batteries. The MOST-PCM combination has the potential to disrupt how we control the temperature in a broad range of applications, from local power production to heating and cooling in electronics systems, to temperature control in automotive and housing. The materials developed in this project have the potential to radically change thermal comfort and energy consumption and give new design opportunities to thermal management systems from the 10-9 to 10 m length scale.

Kasper Moth-Poulsen  – Institut de Ciència de Materials de Barcelona (CSIC – ICMAB)
CoG2020 – Physical Sciences & Engineering (PE5)

FRAGMENT – FRontiers in dust minerAloGical coMposition and its Effects upoN climaTe

Soil dust aerosols are mixtures of different minerals, whose relative abundances, particle size distribution (PSD), shape, surface topography and mixing state influence their effect upon climate. However, Earth System Models typically assume that dust aerosols have a globally uniform composition, neglecting the known regional variations in the mineralogy of the sources. The goal of FRAGMENT is to understand and constrain the global mineralogical composition of dust along with its effects upon climate. The representation of the global dust mineralogy is hindered by our limited knowledge of the global soil mineral content and our incomplete understanding of the emitted dust PSD in terms of its constituent minerals that results from the fragmentation of soil aggregates during wind erosion. The emitted PSD affects the duration of particle transport and thus each mineral’s global distribution, along with its specific effect upon climate. Coincident observations of the emitted dust and soil PSD are scarce and do not characterize the mineralogy. In addition, the existing theoretical paradigms disagree fundamentally on multiple aspects. We will contribute new fundamental understanding of the size-resolved mineralogy of dust at emission and its relationship with the parent soil, based on an unprecedented ensemble of measurement campaigns that have been designed to thoroughly test our theoretical hypotheses. To improve knowledge of the global soil mineral content, we will evaluate and use available remote hyperspectral imaging, which is unprecedented in the context of dust modelling. Our new methods will anticipate the coming innovation of retrieving soil mineralogy through high-quality spaceborne hyperspectral measurements. Finally, we will generate integrated and quantitative knowledge of the role of dust mineralogy in dust-radiation, dust-chemistry and dust-cloud interactions based on modeling experiments constrained with our theoretical innovations and field measurements.

Carlos Pérez García-Pando – Barcelona Supercomputing Centre – Centro Nacional de Supercomputación (BSC – CNS)
CoG2017 – Physical Sciences & Engineering (PE10)

HEALIN – Healthy lifespan inequality: Measurement, trends and determinants

Despite its widespread use and popularity, life expectancy (LE) has two shortcomings. First, its definition only takes into consideration mortality levels, thus ignoring the health status of those who remain alive. Second, LE is an average that does not explain how length of life is distributed across the population. These limitations have generated two strands of research (i.e. the study of ‘health expectancies’ (HE) and ‘lifespan inequality’ (LI)) that, so far, have developed independently from each other. The overarching objective of the HEALIN project is to bring together these research avenues into a coherent whole to get a more comprehensive understanding of contemporary population health dynamics. To attain this goal, I put forward the new concept of ‘healthy lifespan inequality’ (HLI), which is designed to investigate the extent to which healthy lifespans are unequally distributed across the population. The HEALIN project will (i) investigate the trends and determinants of HLI, (ii) assess whether the specific ages and causes that drive changes in HLI are the same ones determining the changes in LE, HE and LI indicators, and (iii) investigate how these indicators behave across and within countries and socio-economic groups. In addition, the project aims at making innovative contributions to the measurement of co-morbidity and to our understanding on how the latter can in turn influence the measurement of health expectancy and healthy lifespan inequality. To attain these objectives, the project will develop path-breaking analytical methods inspired in the models applied for the study of inequality and multidimensional poverty. Besides traditional socio-economic and health data sources, the project will complementary draw from the vastly underutilized health registers for the entire population in Catalonia (7.5 million residents). Their huge size and micro-level design allow investigating trends in HLI and co-morbidity with unprecedented detail.

Iñaki Permanyer – Centre d’Estudis Demogràfics (CED) 
CoG2020 – Social Sciences & Humanities (SH3)

ICON-BIO – Integrated Connectedness for a New Representation of Biology

The aim of the project is to develop a comprehensive framework for generalizing network analytics and fusion paradigms of non-negative matrix factorization to medical data. Heterogeneous, interconnected, systems-level omics data are becoming increasingly available and important in precision medicine. We are seeking to better stratify and subtype patients into risk groups, discover new biomarkers for complex and rare diseases, personalize medical treatment based on genomics and exposures of an individual, and repurpose known drugs to different patient groups. Existing methodologies for dealing with these big data are limited and a paradigm shift is needed to achieve quantitatively and qualitatively better results. The project is motivated by the recent success of non-negative matrix tri-factorization (NMTF) based methods for fusion of heterogeneous data in biomedicine. Though these methods have been known for some time, the availability of large datasets, coupled with modern computational power and efficient optimization methods, allowed for creation and efficient training of complex models that can make a qualitative breakthrough. For example, NMTF has recently achieved unprecedented performance on exceptionally hard problems of simultaneously utilizing the wealth of diverse molecular and clinical data in precision medicine. However, research thus far has been limited to special variants of this problem and used only fixed point methods to address these exciting examples of hard non-convex high-dimensional non-linear optimization problems. The ambition of the project is to develop general data fusion methods, from mathematical models to efficient and scalable software implementation, and apply them to the domain of biomedical informatics. The project will lead to a paradigm shift in biomedical and computational understanding of data and diseases that will open up ways to solving some of the major bottlenecks in precision medicine and other domains.

Natasa Przulj – Barcelona Supercomputing Centre – Centre Nacional de Supercomputación (BSC-CNS)
CoG2017 – Physical Sciences & Engineering (PE6)

LICCI – Local Indicators of Climate Change Impacts. The Contribution of Local Knowledge to Climate Change Research

In the quest to better understand local climate change impacts on physical, biological, and socioeconomic systems and how such impacts are locally perceived, scientists are challenged by the scarcity of grounded data, which has resulted in a call for exploring new data sources. People with a long history of interaction with the environment have developed complex knowledge systems that allow them to detect local impacts of climatic variability, but these insights are absent in climate change research and policy fora. I will bring insights from local knowledge to climate research by 1) providing data on local climate change impacts on physical (e.g., shrinking glaciers) and biological systems (e.g., phenological changes) and on perceptions of climate change impacts on socioeconomic systems (e.g., crop failure due to rainfall patterns change) and 2) testing hypotheses on the global spatial, socioeconomic and demographic distribution of local climate change impacts indicators. Research will last five years.

The first 18 months, Preparation, I will train a team who will develop and implement a data collection protocol and design a web-based platform where citizens can enter information on local climate change impacts indicators.

During the following two years, Data collection, we will train 40 external PhD students to collect project’s data in data-deficient regions and disseminate the platform.

During the last 18 months, Analysis, the core team will use spatial matching and multivariate analysis to test hypotheses related to the spatial, socioeconomic, and demographic distribution of local climate change impacts indicators. External PhD students will analyse local data. Dissemination will be transversal to the project. This project will fill theoretical and spatial gaps on climate change impacts research. It will also improve local capacity to respond to climate change impacts and help bridge epistemological differences between local and scientific knowledge systems.

www.licci.eu

Victoria Reyes-García – Universitat Autònoma de Barcelona  (UAB)
CoG2017 – Social Sciences & Humanities (SH2)

i-NANOSWARMS – Cooperative Intelligence in Swarms of Enzyme-Nanobots

Samuel Sánchez Ordóñez – Institut de Bioenginyeria de Catalunya (IBEC)
CoG2019 – Physical Sciences Engineeering (PE8)

MULTIFLEXO – Hierarchical multiscale modeling of flexoelectricity and related materials properties from first principles

Flexoelectricity, the coupling between an inhomogeneous deformation and the electrical polarization, has emerged a “hot” topic in modern materials science due to its cross-cutting relevance to many phenomena of fundamental and technological interest. Understanding the intriguing physics that governs its behaviour at the nanoscale is crucial to harnessing the potential of strain gradients in practical applications, and such a progress requires a substantial support from theory. In spite of impressive recent advances, first-principles calculations of flexoelectricity remain technically challenging at several levels: first, the breakdown of translational lattice periodicity that a strain gradient entails is problematic to treat in the context of traditional electronic-structure methods; second, the stringent length- and time-scale constraints of direct quantum-mechanical approaches limit the applicability of these methods to real problems, which often involve complex sample shapes and morphologies.

This project is aimed at overcoming these obstacles from their very root, via the development of ground-breaking innovations in electronic-structure and multiscale methodologies, and at using these advances to address a number of pressing physical questions in the context of energy and information technologies. In particular, the objectives of this project are:

(i) identifying the microscopic mechanisms that are most effective at delivering a strong flexoelectric response in a variety of materials;
(ii) understanding how these bulk effects are modified by size, shape and boundary conditions, and how they interact with other material properties;
(iii) supporting the experimental interpretation by critically assessing alternative physical interpretations of the observed effects (e.g. compositional gradients);
(iv) exploring the functionalities enabled by strain gradients in complex materials systems, including 2D crystals, semiconductor nanowires and multiferroics.

Max Stengel – Institut de Ciència de Materials de Barcelona (CSIC-ICMAB)
CoG2016 – Physical Sciences & Engineering (PE3)

SuperComp – Unconventional Superfluids in Quantum Gases with Competing Interactions

Unconventional superfluids, where frictionless flow appears combined with features such as topological excitations or crystalline order, are some of the most surprising collective quantum phases of matter. Although the corresponding topological superfluids and supersolids were originally predicted in condensed matter, ultracold quantum gases provide a more controlled experimental approach to these phases, and promise microscopic access to their exotic properties. A key mechanism towards unconventional superfluidity is the competition in the same system of interactions of different origins, a situation naturally addressed by multicomponent gases. When these interactions have opposite signs, new and surprising phases emerge. A prime example is the ultradilute quantum liquid phase recently observed by my group in a mixture of Bose-Einstein condensates, which is most likely only the first item in a long list of new unconventional phases. The goal of SuperComp is to exploit the full potential of quantum gases with competing interactions to unlock the observation of unconventional superfluid phases that have until now defied experimental realization. To this end, I will explore three distinct mechanisms resulting in unconventional superfluid behavior: quantum fluctuations, engineered dispersion relations, and interactions with non-zero orbital angular momentum. Exploiting combinations of bosonic and fermionic potassium atoms, I will realize novel types of ultradilute quantum liquids, supersolid-like gases and liquids, density-dependent artificial gauge fields, elastic multi-body interactions, and investigate a new approach towards the long-sought px+ipy topological superfluid phase of 2D Fermi gases. These experiments will deepen our understanding of the mechanisms responsible for unconventional superfluidity, and impact not only the field of quantum gases, but also the much broader range of disciplines where unconventional superfluids or superconductors play a key role.

Leticia Tarruell – Institut de Ciències Fotòniques (ICFO)
CoG2020 – Physical Sciences & Engineering (PE2)

BePreSysE – Beyond Precision Cosmology: dealing with Systematic Errors

Over the past 20 years cosmology has made the transition to a precision science: the standard cosmological model has been established and its parameters are now measured with unprecedented precision. But precision is not enough: accuracy is also crucial. Accuracy accounts for systematic errors which can be both on the observational and on the theory/modelling side (and everywhere in between). While there is a well-defined and developed framework for treating statistical errors, there is no established approach for systematic errors. The next decade will see the era of large surveys; a large coordinated effort of the scientific community in the field is on-going to map the cosmos producing an exponentially growing amount of data. This will shrink the statistical errors, making mitigation and control of systematics of the utmost importance. While there are isolated and targeted efforts to quantify systematic errors and propagate them through all the way to the final results, there is no well-established, self-consistent methodology. To go beyond precision cosmology and reap the benefits of the forthcoming observational program, a systematic approach to systematics is needed. Systematics should be interpreted in the most general sense as shifts between the recovered measured values and true values of physical quantities. I propose to develop a comprehensive approach to tackle systematic errors with the goal to uncover and quantify otherwise unknown differences between the interpretation of a measurement and reality. This will require to fully develop, combine and systematize all approaches proposed so far (many pioneered by the PI), develop new ones to fill the gaps, study and explore their interplay and finally test and validate the procedure. Beyond Precision Cosmology: Dealing with Systematic Errors (BePreSysE) will develop a framework to deal with systematics in forthcoming Cosmological surveys which, could, in principle, be applied beyond Cosmology.

Licia Verde – Universitat de Barcelona (UB)
CoG2016 – Physical Sciences & Engineering (PE9)

CERQUTE – Certification of quantum technologies

Given a quantum system, how can one ensure that it (i) is entangled? (ii) random? (iii) secure? (iv) performs a computation correctly? The concept of quantum certification embraces all these questions and CERQUTE’s main goal is to provide the tools to achieve such certification. The need of a new paradigm for quantum certification has emerged as a consequence of the impressive advances on the control of quantum systems. On the one hand, complex many-body quantum systems are prepared in many labs worldwide. On the other hand, quantum information technologies are making the transition to real applications. Quantum certification is a highly transversal concept that covers a broad range of scenarios –from many-body systems to protocols employing few devices– and questions –from theoretical results and experimental demonstrations to commercial products–.

CERQUTE is organized along three research lines that reflect this broadness and inter-disciplinary character:
(A) many-body quantum systems: the objective is to provide the tools to identify quantum properties of many-body quantum systems;
(B) quantum networks: the objective is to characterize networks in the quantum regime;
(C) quantum cryptographic protocols: the objective is to construct cryptography protocols offering certified security. Crucial to achieve these objectives is the development of radically new methods to deal with quantum systems in an efficient way.

Expected outcomes are:
(i) new methods to detect quantum phenomena in the many-body regime,
(ii) new protocols to benchmark quantum simulators and annealers,
(iii) first methods to characterize quantum causality,
(iv) new protocols exploiting simple network geometries
(v) experimentally-friendly cryptographic protocols offering certified security.

CERQUTE goes at the heart of the fundamental question of what distinguishes quantum from classical physics and will provide the concepts and protocols for the certification of quantum phenomena and technologies..

Antonio Acín – Institut de Ciències Fotòniques (ICFO)
AdG2018 – Physical Sciences & Engineering (PE2)

LIPOMET – Dietary Influences on Metastasis: How, When, and Why

We have recently identified metastasis-initiating cells (MICs) in several types of tumors (Nature, 2017)1. Intriguingly, MICs: (i) are exclusive in their ability to generate metastases when transplanted; (ii) express the fatty acid channel CD36 and have a unique lipid metabolic signature; (iii) are exquisitely sensitive to the levels of fat in circulation, thus providing a link between the predisposition of metastasis and dietary fat; (iv) are highly sensitive to CD36 inhibition, which almost completely abolishes their metastatic potential. We still do not know how MICs promote metastasis or how MICs are influenced by dietary fat. In particular: (A) where are MICs located within the tumor, and does this location influence their behavior? How and where do they attach and expand at metastatic sites? (B) Why are MICs so sensitive to specific dietary lipids, and how do these lipids promote metastasis at the molecular and cellular levels? (C) Is the prolonged consumption of a high-fat diet a risk factor for developing metastatic tumors? If so, what are the underlying genetic and epigenetic causes for this effect? Can we revert these causes? To answer these questions, we will combine state-of-the-art in vivo functional models of metastasis, with quantitative metabolomics and proteomics, epigenetic and geographical position (3D) single-cell transcriptomic studies, as well as integrative computational analyses, using preclinical models and patientderived carcinomas of melanoma, oral cancer and breast cancer. We expect our project to provide fundamental insights into the mechanisms of metastasis, and how they are influenced by diet. This is highly relevant as 1) large quantities of fatty acids are typically consumed in Western diets; and 2) metastasis is the leading cause of cancer-related deaths. We also tackle a timely medical unmet need by exploring the therapeutic anti-metastatic potential of targeting fatty acid metabolism in cancer patients.

Salvador Aznar-Benitah – Institut de Recerca Biomèdica (IRB Barcelona)
AdG2017 – Life Sciences (LS4)

ALiEN – Autonomous Linguistic Emergence in neural Networks

Deep neural networks (DNNs) are specialized computational models lacking a standard interface. If a complex task requires different DNNs, an ad-hoc connection must be laboriously designed. Inspired by human language, ALiEN wants to replace such ad-hoc interfaces with generic communication protocols optimized for ease of learning by DNNs that might have different architectures and functions. ALiEN “languages” are not hand-crafted: they emerge by training DNNs to share information through communication, offering the scalability and robustness to noise that is an asset of learned systems. A first set of experiments will study, in tightly controlled settings, the impact of input, training community size and communication channel on the expressiveness and ease of acquisition of emergent protocols. The emergence of general protocols will be encouraged by a training environment characterized by varied inputs and interaction among numerous DNNs. The best emerged protocols will also be taught in a supervised way to new DNNs, with the final aim of establishing a “universal” DNN language. Next, I will explore how emergent protocols can help interfacing out-of-the box, state-of-the-art DNNs, only requiring the addition of light input and output layers to existing pre-trained models. Finally, a simplified home automation use case will demonstrate the usefulness of emergent protocols in a scenario that features some of the complexities to be expected in real-life applications. The project will also thoroughly analyze the emerging protocols, with the concurrent aims of i) identifying and favoring features that make them more expressive and easier to learn; ii) enhancing interpretability; and iii) gathering scientific insights into communication emergence in a non-human “species”. All in all, ALiEN will take a first bold step towards enabling autonomous DNN interaction, and thus genuinely adaptive AI systems.

Marco Baroni – Universitat Pompeu Fabra
AdG 2020 – PE6

residualCRC – Mechanisms Behind Residual Disease in Colorectal Cancer and Modellinf of Therapies that Prevent Relapse

Disease relapse is a major complication in colorectal cancer (CRC). At the time of diagnosis, the majority of patients will present with locoregional disease that can be effectively resected by surgery. This intervention is sufficient to cure the primary disease in most cases. Yet, over the course of the following months or years, around 40% of the patients that underwent resection of the primary tumor with curative intention will relapse, generally in the form of metastatic disease. As these metastases eventually interfere with the function of vital organs such as the liver and lungs, patients that undergo relapse have poor prognosis. Recurrent cancer arises from clinically occult tumor cells that have disseminated to foreign organs (disseminated tumor cells or DTCs) before surgical removal of the primary CRC. Although the time window between surgery and relapse offers a good opportunity to prevent metastasis, current therapies are not effective at eliminating DTCs. Thus, there is an important unmet need to develop strategies to target residual disease. Advances in this area will benefit a large proportion of patients. Despite its clinical relevance, the study of residual disease in CRC has been largely neglected and the principles that govern the behavior of DTCs remain unknown. The main reason for this important knowledge gap is that residual tumor cells are difficult to study in patients, as they remain clinically occult. We have recently generated a unique set of compound mutant mice and organoids that reproduce key features of human metastatic CRC. We propose to leverage these new models to study the biology of residual disease. We will characterize the features of DTCs using single cell transcriptional profiling, analyze the influence of driver mutations on DTC behavior, explore mechanisms of immune evasion during the latency phase, and model DTC latency in vivo and in vitro. Our ultimate goal is to design therapies that prevent disease relapse in CRC.

Eduard Batlle – Institut de Recerca Biomèdica (IRB Barcelona)
AdG 2019 – LS4

TRANSFORMER:  Structural transformations and phase transitions in real-time

Chemical and material sciences are key drivers of our modern economy with transformative impact at all levels of society. In particular, the ability to synthesize and to tailor substances and materials with specific function is all-pervading into modern society. Vital is a firm understanding of structural transformations of molecules and phase transitions of solids as they are omnipresent, e.g. as formation and breakage of molecular bonds, proton motion and isomerization, and as collective phenomena in phase transitions. Gaining insight into the ultrafast correlated dynamics is highly challenging and requires revolutionary methodologies and innovative approaches to capture the dynamics from its onset.

TRANSFORMER will provide unprecedented insight into the real-time electronic and nuclear dynamics of molecular transformations and phase transitions with advanced new methodologies and a multi-faceted approach to the investigation. The project exploits our pioneering achievements in attosecond soft X-ray spectroscopy (XAFS) and laser-induced electron diffraction (LIED) to pinpoint in real-time which electronic states participate at which nuclear configuration. The proposal consists of three objectives:

• We will establish the methodical boundaries of LIED for space-time imaging of isolated molecules.
• We will extract simultaneous and real-time electronic and nuclear information, thus gain insight into the underlying many-body quantum correlations.
• We will use our methodology to realize resolving both, molecular isomerization and a solid’s metal-to-insulator phase transition, in its electronic and nuclear degrees of freedom and in real time.

If successful, TRANSFORMER would undoubtedly provide an unprecedented view into electronic and nuclear dynamics, thereby reaching far beyond the state of the art with clear potential to surpass current limits in molecular and material sciences.

Jens Biegert –Institut de Ciències Fotòniques (ICFO)
AdG2017 – Physical Sciences Engineering (PE4)

ARTSOUNDSCAPES – The sound of special places: exploring rock art soundscapes and the sacred

The ARTSOUNDSCAPES project deals with sound, rock art and sacred landscapes among past hunter-gatherers and early agricultural societies around the world. The potential of sound to stimulate powerful emotions makes it a common medium for conferring places with extraordinary agency. Ethnographic and ethnohistorical sources indicate that these sites are often endowed with a sacred significance and, in many cases, they also receive special treatment, including the production of rock paintings. Despite the aural experience being an integral component of the human condition and a key element in ritual, archaeology has largely been unable to study it systematically. Rock art landscapes are no exception and, although some studies have been made, they have largely been reproached for their lack of scientific rigour and subjectivity. ARTSOUNDSCAPES will fully address this weakness by investigating the perception of sound in rock art landscapes from an interdisciplinary approach. Borrowing methods developed in acoustic engineering, the project will assess, from an objective and quantitative perspective, the acoustic properties of rock art landscapes in selected areas around the world: the Western/Central Mediterranean in Europe, Siberia in Asia, Namibia in Africa and the Sonoran Desert in North America.

Human experiences associated with altered or mystical states invoked by the identified special sonic characteristics of these landscapes will be further tested by exploring the psychoacoustic effects these soundscapes have on people and their neural correlate to brain activity. The project will also thoroughly survey ethnographic attitudes to sacred soundscapes based on both current premodern societies and ethnohistorical sources. The groundbreaking combination of this array of interdisciplinary approaches will facilitate the ultimate aim of the project: to propose a phenomenological understanding of sacred soundscapes among late hunter-gatherers and early agriculturalists around the world.

Facebook: www.facebook.com/artsoundscapes

Web page: www.archaeoacoustics.ub.edu

Margarita Díaz-Andreu – Universitat de Barcelona (UB)
AdG2017 – Social Sciences & Humanities (SH6)

MARKET POWER – Labor Market Risk and Skill Diversity: Implications for Efficiency, Policy, and Estimation

In the last four decades, there have been a number of significant secular trends in the advanced economies around the world. Wage inequality has risen sharply, and most of the wage gains have been appropriated by the top 1%. In addition, labor market dynamism and new startups have declined, the labor share of total output has fallen, low skilled wages have stagnated, and there has been reallocation of production from small to superstar firms. During the same four decades, there has also been a sharp secular increase in market power. Firms set higher prices, profit rates are higher, and scale economies are up. In this proposal, I address the question whether these secular trends are related. Specifically, I ask whether the rise of market power has caused these profound macroeconomic changes. The objective is to uncover economic mechanisms that help understand this fundamental transformation and the implications for efficiency and welfare. I propose to investigate both the causes of the rise in market power and its macroeconomic consequences. I distinguish between causes that stem inherently from the market structure (such as antitrust enforcement and Mergers & Acquisitions) and those that result from technological change (economies of scale, intangible assets, and network externalities). Methodologically, this research proposal aims to contribute to the literature on three fronts: 1. the measurement of markups, 2. to derive theoretical results linking market power and macroeconomic consequences, 3. to estimate and quantitatively evaluate these models. The close link between the macroeconomic consequences and the causes of market power renders this a research proposal at the intersection of macro/labor, industrial organization and law & economics. The objective is to inform the policy debate: how to keep market power under control in order to remediate its macroeconomic consequences that were hitherto considered independent.

Jan Eeckhout – Universitat Pompeu Fabra (UPF)
AdG 2019 – Social Sciences & Humanities (SH1)

eNANO – Free electrons as ultrafast nanoscale probes 

With eNANO I will introduce a disruptive approach toward controlling and understanding the dynamical response of material nanostructures, expanding nanoscience and nanotechnology in unprecedented directions. Specifically, I intend to inaugurate the field of free-electron nanoelectronics, whereby electrons evolving in the vacuum regions defined by nanostructures will be generated, guided, and sampled at the nanoscale, thus acting as probes to excite, detect, image, and spectrally resolve polaritonic modes (e.g., plasmons, optical phonons, and excitons) with atomic precision over sub-femtosecond timescales. I will exploit the wave nature of electrons, extending the principles of nanophotonics from photons to electrons, therefore gaining in spatial resolution (by relying on the large reduction in wavelength) and strength of interaction (mediated by Coulomb fields, which in contrast to photons render nonlinear interactions ubiquitous when using free electrons). I will develop the theoretical and computational tools required to investigate this unexplored scenario, covering a wide range of free-electron energies, their elastic interactions with the material atomic structures, and their inelastic coupling to nanoscale dynamical excitations. Equipped with these techniques, I will further address four challenges of major scientific interest:

(i) the fundamental limits to the space, time, and energy resolutions achievable with free electrons;
(ii) the foundations and feasibility of pump-probe spectral microscopy at the single-electron level;
(iii) the exploration of quantum-optics phenomena by means of free electrons; and
(iv) the unique perspectives and potential offered by vertically confined free-electrons in 2D crystals.

I will face these research frontiers by combining knowledge from different areas through a multidisciplinary theory group, in close collaboration with leading experimentalists, pursuing a radically new approach to study and control the nanoworld.

F. Javier García de Abajo – Institut de Ciències Fotòniques (ICFO)
AdG2017 –  Physical & Engineering Sciences (PE3)

NANO-MEMEC – Membrane-based nano-mechanobiology: Role of mechanical forces in remodelling the spatiotemporal nanoarchitecture of the plasma membrane

Through evolution, cells have developed the exquisite ability to sense, transduce and integrate mechanical and biochemical signals (i.e. mechanobiology) to generate appropriate responses. These key events are rooted at the molecular and nanoscale levels, a size regime difficult to access, hindering our progress towards mechanistic understanding of mechanobiology. Recent evidence from my Lab (and others) shows that the lateral nanoscale organisation of mechanosensitive membrane receptors and signalling molecules is crucial for cell function. Yet, current models of mechanosensing are based on force-induced molecular conformations, completely overlooking the chief role of mechanical forces on the nanoscale spatiotemporal organisation of the plasma membrane.
The GOAL of NANO-MEMEC is to provide mechanistic understanding on the role of mechanical stimuli in the spatiotemporal nanoarchitecture of adhesion signalling platforms at the cell membrane. To overcome the technical challenges of probing these processes at the relevant spatiotemporal scales, I will exploit cuttingedge biophysical tools exclusively developed in my Lab that combine super-resolution optical nanoscopy and single molecule dynamics in conjunction with simultaneous mechanical stimulation of living cells. Using this integrated approach, I will:

First: dissect mechanical and biochemical coupling of membrane mechanosensing at the nanoscale.
Second: visualise the coordinated recruitment of integrin-associated signalling proteins in response to force, i.e., mechanotransduction.
Third: test how force-induced spatiotemporal membrane remodelling influences the migratory capacity of immune cells, i.e., mechanoresponse.

NANO-MEMEC conveys a new fundamental concept to the field of mechanobiology: the roles of mechanical stimuli in the dynamic remodelling of membrane nanocompartments, modulating signal transduction and ultimately affecting cell response, opening new-fangled research avenues in the years to come.

Maria F. García Parajo – Institut de Ciències Fotòniques (ICFO)
AdG2017 –  Life Sciences (LS1)

RLeap – From Data-based to Model-based AI: Representation Learning for Planning

Two of the main research threads in AI revolve around the development of data-based learners capable of inferring behavior and functions from experience and data, and model-based solvers capable of tackling well-defined but intractable models like SAT, classical planning, and Bayesian networks. Learners, and in particular deep learners, have achieved considerable success but result in black boxes that do not have the flexibility, transparency, and generality of their model-based counterparts. Solvers, on the other hand, require models which are hard to build by hand. RLeap is aimed at achieving an integration of learners and solvers in the context of planning by addressing and solving the problem of learning first-order planning representations from raw perceptions alone without using any prior symbolic knowledge. The ability to construct first-order symbolic representations and using them for expressing, communicating, achieving, and recognizing goals is a main component of human intelligence and a fundamental, open research problem in AI. The success of RLeap requires the development of radically new ideas and methods that will build on those of a number of related areas that include planning, learning, knowledge representation, combinatorial optimization and SAT. The approach to be pursued is based on a clear separation between learning the symbolic representations themselves, that is cast as a combinatorial problem, and learning the interpretations of those representations, that is cast as a supervised learning problem from targets obtained from the first part. RLeap will address both problems, not just in the planning setting but in the generalized planning setting as well where plans are general strategies. The project can make a significant difference in how general, explainable, and trustworthy AI can be understood and achieved. The PI has made key contribution to the main themes of the project that make him uniquely qualified to carry it forward.

Héctor Geffner – Universitat Pompeu Fabra (UPF)
AdG 2019 – Physical Sciences and Engineering (PE6)

MUTANOMICS – Determining in vivo protein structures and understanding genetic interactions using deep mutagenesis

The goal of my research is to understand mutations and how they interact to alter phenotypes and disease. We recently initiated a new research direction that uses systematic (‘deep’) mutagenesis to quantify, understand, and predict how diverse mutations interact non-additively within and between molecules to affect phenotypes at multiple scales. Very excitingly, we have also shown that quantifying genetic interactions by deep mutagenesis provides sufficient information to determine the 3D structures of proteins. In this project we will leverage this experience in deep mutagenesis and computational modelling to address three specific aims: 1. To develop simple generic experimental and computational methods to determine the in vivo structures of proteins using deep mutagenesis and to apply these methods to solve the structures of domains of unknown structure. 2. To use deep mutagenesis and computational modelling to understand how mutations globally interact within and between molecules, when these interactions can – and cannot – be predicted from phenotypic measurements alone, and how these interactions alter in response to changes in gene expression. 3. To use deep mutagenesis to understand the cellular toxicity of pathological prion-like domains and to reveal the in vivo structures of these ‘unstructured’ regions, as well as those of disordered proteins that function as agents of protein-based epigenetic inheritance. Taken together, this will provide rich insights into how mutations combine to alter phenotypes, a question of central importance to evolution, engineering, and human disease. It will also develop methods that use deep mutagenesis to determine protein structures, including of intrinsically disordered proteins relevant to disease and epigenetic inheritance. Our goal is to develop techniques that will allow labs across the world to use deep mutagenesis to solve protein structures, including potentially in large-scale systematic projects.

Ben Lehner – Centre de Regulació Genòmica (CRG)
AdG 2019 – Life Sciences (LS2)

NOQIA – NOvel Quantum simulators – connectIng Areas

Quantum simulators (QS) are experimental systems that allow mimic hard to simulate models of condensed matter, high energy physics and beyond. QS have various platforms: from ultracold atoms and ions to superconducting qubits. They constitute the important pillar of quantum technologies (QT), and promise future applications in chemistry, material science and optimization problems. Over the last decade, QS were particularly successful in mimicking topological effects in physics (TEP) and in developing accurate quantum validation/certification (QVC) methods. NOQIA is a theory project, aimed at introducing the established field of QS+TEP+QVC into two novel areas: physics of ultrafast phenomena and attoscience (AS) on one side, and quantum machine learning (ML) and neural networks (NN) on the other. This will open up new horizons/opportunities for research both in AS and in ML/NN. For instance, in AS we will address the question if intense laser physics may serve as a tool to detect topological effects in solid state and strongly correlated systems. We will study response of matter to laser pulses carrying topological signatures, to determine if they can induce topological effects in targets. We will design/analyze QS using trapped atoms to understand and detect TEP in the AS. On the ML/NN side, we will apply classical ML to analyze, design and control QS for topological systems, in order to understand and optimize them. Conversely, we will transfer many-body techniques to ML in order to analyze and possibly improve performance of classical machine learning. We will design and analyze quantum neural network devices that will employ topology in order to achieve robust quantum memory or information processing. We will design/study attractor neural networks with topological stationary states, or feed-forward networks with topological Floquet and time-crystal states. Both in AS and ML/NN, NOQIA will rely on quantum validation and certification protocols and techniques.

Maciej Lewenstein –Institut de Ciències Fotòniques (ICFO)
AdG2018 – Physical Sciences Engineering (PE2)

APMPAL-HET – Asset Prices and Macro Policy when Agents Learn and are Heterogeneous

Based on the APMPAL (ERC) project we continue to develop the frameworks of internal rationality (IR) and optimal signal extraction (OSE). Under IR investors/consumers behave rationally given their subjective beliefs about prices, these beliefs are compatible with data. Under OSE the government has partial information, it knows how policy influences observed variables and signal extraction. We develop further the foundations of IR and OSE with an emphasis on heterogeneous agents. We study sovereign bond crisis and heterogeneity of beliefs in asset pricing models under IR, using survey data on expectations. Under IR the assets’ stochastic discount factor depends on the agents’ decision function and beliefs; this modifies some key asset pricing results. We extend OSE to models with state variables, forward-looking constraints and heterogeneity. Under IR agents’ prior beliefs determine the effects of a policy reform. If the government does not observe prior beliefs it has partial information, thus OSE should be used to analyse policy reforms under IR. If IR heterogeneous workers forecast their productivity either from their own wage or their neighbours’ in a network, low current wages discourage search and human capital accumulation, leading to low productivity. This can explain low development of a country or social exclusion of a group. Worker subsidies redistribute wealth and can increase productivity if they “teach” agents to exit a low-wage state. We build DSGE models under IR for prediction and policy analysis. We develop time-series tools for predicting macro and asset market variables, using information available to the analyst, and we introduce non-linearities and survey expectations using insights from models under IR. We study how IR and OSE change the view on macro policy issues such as tax smoothing, debt management, Taylor rule, level of inflation, fiscal/monetary policy coordination, factor taxation or redistribution.

Albert Marcet – Universitat Autònoma de Barcelona (UAB)
AdG2017 – Social Sciences & Humanities (SH1)

NOVOFLAT – Escaping from Flatland by “de novo” Catalytic Decarboxylation Techniques

Although cross-coupling reactions have become one of the pillars of modern chemical synthesis, the ability to forge sp3–sp3 bonds with improved flexibility, practicality, predictable site-selectivity, preparative utility, stereocontrol and with nearly zero-generation of waste has eluded chemists for decades, remaining a major challenge and an uncharted cartography in catalytic endeavours. The successful realization of this goal will represent a paradigm shift from the standard logic of organic synthesis in both basic and applied research, as increasing the number of sp3-hybridized carbon atoms has become a necessary goal in the drug discovery pipeline. NOVOFLAT offers a pioneering approach for forging sp3–sp3 linkages via a triple catalytic cascade that enables an unprecedented intramolecular decarboxylation of simple and available carboxylic acid esters with CO2 as the sole byproduct. As ester derivatives simply derive from naturally-occurring carboxylic acids and alcohols, this proposal will allow to rapidly access sp3–sp3 linkages with different electronic and steric requirements, thus providing an invaluable opportunity to streamline the discovery of important architectures with applications across the molecular sciences. Preliminary results demonstrate the feasibility to provide “a la carte” predictable tool that chemists could use to control the site where the sp3–sp3 bond-formation takes place in both aliphatic and cyclic frameworks, even at remote sp3 sites. In addition, our general principle offers an unrecognized opportunity to simultaneously construct sp3–sp3 linkages and control the stereochemistry at remote sp3 sites. In this manner, NOVOFLAT will not only provide new dogmas in retrosynthetic analysis by fundamentally altering the way sp3–sp3 bonds are made, but also open new vistas in “chain-walking” reactions, as the incorporation of chirality throughout the alkyl side-chain constitutes “terra incognita” in these technologies.

Ruben Martin – Institut Català d’Investigació Química (ICIQ)
AdG 2019 – Physical Sciences & Engineering (PE5)

MiniEmbryoBlueprint – The mammalian body plan blueprint, an in vitro approach

The development of an embryo requires the spatially structured emergence of tissues and organs. This process relies on the early establishment of a coordinate system in the form of three orthogonal axes that act as a reference for laying down the body plan, a template for the organism. Genetic analysis of this process has revealed an underlying transcriptional blueprint that links the coordinate system and the body plan. However, the way in which the gene products contribute to the emergence of the body plan remains an open question. A reason for this is that this process involves feedbacks and integration between the activity of Gene Regulatory Networks (GRNs) and the mechanics of multicellular ensembles, and that probing this relationship is experimentally challenging. In the case of mammalian embryos, which are particularly important as models for human development, our gaps in knowledge of these events are larger than in other organisms. This is partly due to the challenges associated with uterine development but also, and increasingly, because of the cost of mice and the difficulty of obtaining large numbers of embryos, as required for mechanistic experiments. In this project we shall use gastruloids, a novel and versatile Pluripotent Stem Cells based experimental system that we have developed for the study of mammalian development, to gain insights into the molecular and cellular basis underlying the emergence of the mammalian body plan. Gastruloids lack anterior neural structures and over a period of five days become organized in the fashion of a midgestation mouse embryo. We shall use the experimental versatility of the Gastruloid system to probe into the functional relationships between the mechanical activities of multicellular ensembles and the dynamics of GRNs that underlie the emergence of the mammalian body plan.

Alfonso Martínez Arias – Universitat Pompeu Fafra (UPF)
AdG2018 – Life Sciences (SL3)

CLIPOFF-CHEM – Clip-off Chemistry: Design and Synthesis of New Materials via Programmable Disassembly of Reticular Materials

Historically, innovations in synthetic methods and reactions have changed the way scientists think about designing and synthesizing materials and molecules. Indeed, novel synthetic methods not only unlock access to previously unattainable structures, but also inspire new concepts as to how we design and build materials to address global social, economic and industrial needs. The project that I propose here, CLIPOFF-CHEM, centers on the demonstration of a novel synthetic methodology that I have named Clip-off Chemistry. Unlike most state-of-the-art synthetic approaches, which use bottom-up strategies to link atoms and molecules through the formation of new bonds, Clip-off Chemistry is based instead on the selective cleavage of existing bonds in reticular materials, providing precise spatial control over bond cleavage. In reticular materials, this cleavage can be programmed to enable the synthesis of limitless materials varying by composition (from organic to metal-organic), dimensionality (from 3-D to 0-D) and size-scale (from macro- to nanoscale). Accordingly, in CLIPOFF-CHEM, I will employ clip-off synthesis to prepare a diverse collection of new materials and molecules, including new 3-D metal-organic frameworks (MOFs), low-dimensional (2-D and 1-D) materials, organic polymers, metal-organic polyhedra (MOPs), complexes and macrocycles. Our work will encompass 1) synthesis of the reticular material precursors (MOFs, COFs and MOPs) that incorporate non-cleavable and cleavable (alkene/alkyne) groups in precise positions of their structures; and 2) cleavage of alkene/alkyne groups through ozonolysis to produce the targeted materials. As the resultant products will be novel, we will also endeavor to identify and characterize any unprecedented structural or functional properties of them. I believe that CLIPOFF-CHEM will provide the global scientific community with an innovative methodology for the design and synthesis of new functional molecules and materials.

Daniel Maspoch – Institut Català de Nanociència i Nanotecnologia
AdG 2020 – PE5

STEM-AGING – Tissue regeneration and aging: the decisive quiescent stem-cell state

The basic mechanisms of stem cell malfunction during aging are poorly understood even though they underlie the regenerative decline of most organs and tissues as we age. Based on our recent contributions (Nature 2014, Nature 2016), the fields of tissue regeneration and aging converge on the key role of the quiescent state, the preferred state of stem cells in low turnover tissues such as skeletal muscle. Our unifying hypothesis is that stem-cell quiescence maintenance, which requires active proteostasis (protein homeostasis), lies at the basis of stemness, and that its substitution by a senescence state in aging impairs regeneration. How these variables connect to drive stem cell aging is not known. Crucial experimental systems in this proposal are sensitive reporter mice for proteostasis, senescence and quiescence/fate in aging muscle stem cells. The project is divided as follows: Objective 1. Proteostasis and stem cell quiescence maintenance: tracing proteostasis in quiescent stem cells from autophagy and chaperone-mediated autophagy (CMA) reporter mice during aging / impact of autophagy/CMA loss on quiescence and regeneration / molecular regulators of proteostasis. Objective 2. Proteostasis and quiescent stem cell heterogeneity and fate: asymmetric segregation of proteotoxic waste as an instructor of stem cell heterogeneity and regenerative fate. Objective 3. The quiescence-to-senescence-switch in aging muscle stem cells: tracing and isolating senescent stem cells in senescence-cell reporter mice during aging / impact of senescent cell ablation on regenerating aged muscle. Objective 4. Circadian regulation in the quiescent stem-cell state: impact of aging on circadian rhythms and consequences for quiescence maintenance and regeneration. We expect that completion of these objectives will provide new fundamental knowledge on stem-cell biology, regeneration and aging.

Pura Muñoz-Cánoves – Universitat Pompeu Fabra (UPF)
AdG2016 – Life Sciences (LS4)

LUNG-BIOREPAIR – Engineering a lung bacteria to treat idiopatic lung fibrosis and other non-infectious lung diseases

Lung diseases are a leading cause of mortality worldwide. Dysregulation of immunomodulatory molecules plays a key role in many pulmonary diseases, including lung cancer, idiopathic pulmonary fibrosis (IPF) and infections. In IPF acute or chronic inflammation results in senescence of the alveolar cells with telomere shortening and/or dysregulation of miRNAs. Modulating the immune response directly or its downstream repercussions could be a possible way to help treat lung diseases. Systemic treatment with immunomodulatory molecules however, can have several drawbacks and include toxic side effects in other organs, the need for continuous delivery and a high cost of production. Similarly, treating immunomodulatory repercussions such as telomere shortening or abnormal miRNA expression in target cells is not easy due to the lack of a technology that efficiently and specifically delivers RNA. Furthermore, viral transformation can result in toxicity and is associated with high costs. To circumvent these problems, we aim to engineer the genome-reduced lung bacterium Mycoplasma pneumoniae as a vector to locally express immunomodulatory proteins, and/or to deliver protein¬–RNA complexes into alveolar cells (Mycovector). M. pneumoniae does not have a cell wall, it directly releases secreted biomolecules into the medium, it does not recombine, it has a unique genetic code that prevents the transfer of genes to other bacteria and we have a non-pathogenic engineered version of it. To design this Mycovector, we will combine our experience in this organism with our know-how in protein design (http://foldxsuite.crg.eu/). We will use our Mycovector expressing different combinations of active biomolecules to treat bleomycin-induced IPF in mice. This project will not only offer new insights into the treatment of a currently incurable disease, but also show that bacterial chassis can be used in other organs different from the gut paving the way to other applications in human health.

Luis Serrano – Centre de Regulació Genòmica
AdG 2020 – LS9

LEIT – Lossless information for Emerging Information Technologies

In nanoelectronic circuits, interconnects use more energy than microprocessors, a situation clearly undesirable for e.g. autonomous Internet of Things applications based on charge and other information tokens. Overcoming this issue and minimising overall power consumption will be of paramount importance as we move towards Beyond-CMOS circuits. A novel approach is required. In LEIT I propose to investigate phonons as information carriers with typical ultralow energies of a fraction of a meV. As quanta of lattice vibrations, the high interactivity of phonons presents two key challenges: phonon-phonon scattering and losses in waveguides caused by interaction with e.g. lattice defects. I propose to overcome this by engineering phonon-phonon scattering in custom-designed phononic crystal-based structures moving towards narrow frequencies and non-interacting phonons at room temperature. These structures will exhibit a unique combination of features to allow phonon filtering, reflection and confinement, as well as transmission from one element (source) to another (modulator and waveguides), all of which will serve to direct and guide the phonon waves. Phonon losses will be minimised even eradicated by using topological phononic waveguides to transmit phonons over micrometre distances. The technological platforms will be made from silicon (Si) and Si-compatible materials, also incorporating transition metal dichalcogenides in order to reach the higher frequencies. In LEIT I will draw on my extensive experimental research on phonons in semiconductor nanostructures, Si membranes and phononic crystals to demonstrate the viability of acoustic phonons as low-energy information carriers. By doing so I will lay the scientific and technological foundations of a new phononics-based approach to information processing, offering a means of transmitting information that is extremely low-power and lossless, while also compact and integrable with Si-technologies.

Clivia Sotomayor – Institut Català de Nanociència i Nanotecnologia (ICN2)
AdG 2019 – Physical Sciences & Engineering (PE7)

EpiFold – Engineering epithelial shape and mechanics: from synthetic morphogenesis to biohybrid devices

All surfaces of our body, both internal and external, are covered by thin cellular layers called epithelia. Epithelia are responsible for fundamental physiological functions such as morphogenesis, compartmentalization, filtration, transport, environmental sensing and protection against pathogens. These functions are determined by the three-dimensional (3D) shape and mechanics of epithelia. However, how mechanical processes such as deformation, growth, remodeling and flow combine to enable functional 3D structures is largely unknown. Here we propose technological and conceptual advances to unveil the engineering principles that govern epithelial shape and mechanics in 3D, and to apply these principles towards the design of a new generation of biohybrid devices. By combining micropatterning, microfluidics, optogenetics and mechanical engineering we will implement an experimental platform to (1) sculpt epithelia of controlled geometry, (2) map the stress and strain tensors and luminal pressure, and (3) control these variables from the subcellular to the tissue levels. We will use this technology to engineer the elementary building blocks of epithelial morphogenesis and to reverse-engineer the shape and mechanics of intestinal organoids. We will then apply these engineering principles to build biohybrid devices based on micropatterned 3D epithelia actuated through optogenetic and mechanical control. We expect this project to enable, for the first time, full experimental access to the 3D mechanics of epithelial tissues, and to unveil the mechanical principles by which these tissues adopt and sustain their shape. Finally, our project will set the stage for a new generation of biohybrid optomechanical devices. By harnessing the capability of 3D epithelia to sense and respond to chemical and mechanical stimuli, to self-power and self-repair, and to secrete, filter, digest and transport molecules, these devices will hold unique potential to power functions in soft robots.

Xavier Trepat – Institut de Bioenginyeria de Catalunya (IBEC)
AdG 2019 – Physical Sciences & Engineering (PE8)

GAPT – Geometric Analysis and Potential Theory

This project aims to solve several long standing questions in geometric analysis by combining techniques from harmonic analysis, geometric measure theory, and free boundary problems. These questions deal with harmonic measure and caloric measure, square functions and rectifiability, and some related free boundary problems. A common feature is that their study involves multiscale methods from Littlewood-Paley theory and quantitative rectifiability. Harmonic measure is a basic tool for the solution of the Dirichlet problem for the Laplace equation. The study of this notion is an old question which goes back to the 1910’s, at least. Recently there have been some striking advances on this topic, in part motivated by the deeper understanding of the connection between Riesz transforms and rectifiability. However, there are still related open compelling questions that this project aims to explore. The main one consists of finding a sharp bound for the Hausdorff dimension of harmonic measure. Other challenging questions arise in the parabolic setting, where the connection between the caloric measure associated with the heat equation and parabolic rectifiability is not well understood. Also, the study of the Lipschitz removability for the heat equation is more difficult than in the case of the Laplace equation. Another exciting topic that will be studied by this project deals with the relationship between rectifiability, square functions, and some free boundary problems. An important question concerns the characterization of the L^2 boundedness of Riesz transforms in terms of the Jones-Wolff potential, essential to understand the behavior of Lipschitz harmonic capacity under bilipschitz maps. Square functions, techniques of quantitative rectifiability, and monotonicity formulas from free boundary problems also appear in the study of the blowups of the singular set in the two phase problem for harmonic measure and in problems of unique continuation at the boundary.

Xavier Tolsa – Universitat Autònoma de Barcelona
AdG 2020 – PE1

EVOCLIM – Behavioral-evolutionary analysis of climate policy: Bounded rationality, markets and social interactions

Distinct climate policies are studied with incomparable approaches involving unique criteria and impacts. I propose to unite core features of such approaches within a behavioral-evolutionary framework, offering three advantages: evaluate the effectiveness of very different climate policy instruments in a consistent and comparative way; examine policy mixes by considering interaction between instruments from a behavioral as well as systemic perspective; and simultaneously assessing policy impacts mediated by markets and social interactions. The key novelty is linking climate policies to populations of heterogeneous consumer and producers characterized by bounded rationality and social interactions. The resulting models will be used to assess the performance of policy instruments – such as various carbon pricing and information provision instruments – in terms of employment, equity and CO2 emissions.

The approach is guided by 5 goals:

(1) test robustness of insights on carbon pricing from benchmark approaches that assume representative, rational agents;
(2) test contested views on joint employment-climate effects of shifting taxes from labor to carbon;
(3) examine various instruments of information provision under distinct assumptions about social preferences and interactions;
(4) study regulation of commercial advertising as a climate policy option in the context of status-seeking and high-carbon consumption; and
(5) explore behavioral roots of energy/carbon rebound.

The research has a general, conceptual-theoretical rather than a particular country focus. Given the complexity of the developed models, it involves numerical analyses with parameter values in realistic ranges, partly supported by insights from questionnaire-based surveys among consumers and firms. One survey examines information provision instruments and social interaction channels, while another assesses behavioral foundations of rebound. The project will culminate in improved advice on climate policy.

Jeroen van den Bergh – Universitat Autònoma de Barcelona (UAB)
AdG2016 – Social Sciences & Humanitites (SH2)

LiquOrg – Do liquid crystal-like phases of proteins organize membrane compartments?

We are in the midst of a revolution in our understanding of the internal organization of cells. In the 1950s we learned that lipid bilayer-based membranes serve as containers (organelles) within the cytoplasm. Now we are learning that liquid-like “membrane-less” organelles i.e. without any container, self-assemble based on “liquid-liquid” phase separations. We propose the seemingly radical idea that membrane-bounded organelles– like their membrane-less counterparts- are stabilized or even templated by analogous phase separations of their surface proteins into largely planar liquids akin to liquid crystals. Our unique Synergy team is organized specifically to test this “liquid crystal hypothesis” on the cell’s secretory compartments – ER exit sites (ERES) and the Golgi stack – by employing our complementary skills in physics, physical chemistry, biochemistry and cell biology. We hypothesize based on pilot experiments evidence that the ERES and Golgi self-organize as a multi-layered series of adherent liquid crystal-like phases of “golgin” and similar proteins which surround and enclose their membranes. Their differential adhesion and repulsion would specify the topology and dynamics of the membrane compartments. If this is true, it will literally rewrite the history of cell biology. We will test the ‘liquid crystal’ hypothesis directly, systematically, and quantitatively on an unprecedented scale to either modify/disprove it or place it on a firm rigorous footing. Experiments (Aim 1) with 13 pure golgins in cis and trans pairwise combinations will establish their foundational physical chemistry. Surgically engineered changes in golgins/ERES proteins will alter the rank order (hierarchy) of their affinities for each other and link phase separation physics to cell biology (Aim 2) and be used to establish the structural basis of phase separations and their specificity, and the potential for self-assembly of wholly synthetic biological organelles (Aim 3).

Vivek Malhotra – Centre de Regulació Genòmica (CRG)
SyG 2020

BCLLatlas – Single-cell genomics to comprehensively understand healthy B-cell maturation and transformation to chronic lymphocytic leukemia

Unbiased analyses of the molecular make up of single cells are revolutionizing our understanding of cell differentiation and cancer. Over the last years, our groups have characterized the molecular features of normal B-cell subpopulations and of pools of leukemic cells from chronic lymphocytic leukemia (CLL), the most frequent leukemia in the Western world. These analyses have revealed that CLL subtypes are related to different B-cell maturation stages, and that they can show a complex subclonal architecture. Such subclonality is dynamically modulated during the course of the disease, and has deep implications in CLL biology, clinical aggressiveness and treatment responses. In this scenario, BCLL@las aims at deciphering the origin and molecular anatomy of CLL during the entire life history of the disease by generating genetic, transcriptional and epigenetic maps of hundred-thousands of single cells across locations, time points and individuals.

We plan to fulfill four major objectives:
1) To generate a comprehensive atlas of normal B-cell maturation,
2) To understand the initial steps of neoplastic transformation through the analysis of minute B-cell monoclonal proliferations in healthy individuals,
3) To decipher the cellular diversity and clonal architecture of CLL at diagnosis, and
4) To characterize the single-cell subclonal dynamics of CLL during disease evolution and treatment response.

To reach these goals, BCLL@las gathers together four teams with complementary expertise in B-cell biology, clinics and pathology of CLL, genomics, transcriptomics, epigenomics, sequencing technologies, single-cell profiling and computational biology. This, together with the richness of the available CLL samples and the technical and analytical depth of BCLL@las shall lead to unprecedented insights into the origin and evolution of cancer in the precision medicine era.

Iñaki Martin-Subero – Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
SyG 2018 – SyG3LSb

CARBOCENTRE – Activity-Based Profiling of Glycoprocessing Enzymes for Human Health and a Sustainable Society

Enzymes that produce and degrade oligosaccharides and glycoconjugates are present in all kingdoms of life. The ability to visualize, modulate and understand these carbohydrate-active enzymes (CAZymes) therefore offers great potential for human health and sustainable industries. To provide a “disruptive” shift in our understanding, we adopt in this proposal a multidisciplinary approach combining structural biology, enzymology, computational chemistry, organic synthesis, and chemical biology, with major leaders in these fields part of our CARBOCENTRE Synergy Team. Three fundamental strands will specifically target and ‘capture’ glycoprocessing enzyme active sites. Biochemical and 3-D structural analyses will inform computational dissection of the reaction coordinate of key enzymes for human health and biotechnology processes. Building on our founding work on retaining glycosidases we will also target inverting glycosidases and glycosyltransferases. Following fundamental analyses, our probes will feed research in two major application domains of human health and biotechnology: 1. To provide visualization, diagnosis, and inhibitor assays and clinical lead compounds for enzymes in cancers and genetic diseases (lysosomal storage disorders). 2. To explore the natural diversity of CAZymes and to discover, quantify and optimize new enzymes for food and household applications and for biomass conversion to biofuels. In an iterative cycle, structural biology and enzymology (Davies, York), will inform, through structures of enzymes and enzyme-inhibitor complexes, theoretical and computational chemistry (Rovira, Barcelona), which in turn will guide the design and synthesis (Overkleeft, Leiden), of inhibitors and activity-based probes for ensuing chemical biology studies in the domains of biomedicine and biotechnology.

Carme Rovira i Virgili – Universitat de Barcelona (UB)
SyG 2020

BIOMECANET – Integration of the Biochemical and Mechanical Networks of Cell Division

Cellular and sub-cellular organisation at the micrometre length scale ultimately reflects the activity of molecular networks that harness chemical energy to perform precise mechanical work, create functional spatial gradients, and sustain timely temporal changes in molecular activities. In eukaryotic cell division, the biochemical oscillations of the cell cycle drive dramatic morphological changes of the cytoskeleton necessary for bi-orientation of chromosomes and for their subsequent delivery into two daughter cells. This mechanism is at the heart of biology, but it is poorly understood and hard to address because it involves out-of-equilibrium chemistry of many components and Brownian mechanics of the cytoskeleton. BIOMECANET’s extraordinarily ambitious goal is to unravel this interplay by re-engineering it in vitro and by modelling it in silico. To achieve this, BIOMECANET will mobilize an unrivalled catalogue of purified human proteins to reconstitute four fundamental and interlinked biochemical and mechanical protein networks: 1) the cell cycle oscillator with the spindle assembly checkpoint; 2) the metaphase spindle; 3) the chromosome bi-orientation machinery of kinetochores; and 4) the central spindle and its links with the actin cytoskeleton required for cell fission. Then, BIOMECANET will combine these reconstituted networks, integrating temporal control and mechanical forces to analyse the emergence of complex life-like biological function, thus elevating scale and scope of in vitro reconstitutions to an entirely new level. Crucial to the attainment of BIOMECANET’s long-term goals is the synergetic alliance of two biochemists having pioneered different types of biochemical reconstitutions in the complementary areas of cell cycle and chromosome biology (Musacchio) and the cytoskeleton (Surrey), and a theoretician having pioneered physically faithful modelling and simulation of intracellular systems (Nédélec).

Thomas Surrey – Centre de Regulació Genòmica (CRG)
SyG 2020

IT4-TALL – Clinical translation of a novel CD1a-directed CAR for relapse/refractory cortical T-cell Acute Lymphoblastic Leukemia: feasibility, efficacy and safety

Immunotherapy has revolutionized cancer treatment over the last decade. Adoptive cell immunotherapy with T-cells genetically redirected to a tumor-specific antigen using a chimeric antigen receptor (CAR) has achieved impressive response rates in advanced B-cell acute lymphoblastic leukemia (B-ALL). CAR T-cell strategies beyond B-cell tumors are, however, hampered by expected toxicities, owing to the lack of bona fide therapeutic and safe antigens. Indeed, there are no immunotherapeutic therapies (including CAR T-cells) approved for T-cell malignancies (T-ALL or T-cell lymphomas), as the shared expression of target antigens between CAR T-cells and T-blasts induces CAR T-cell fratricide and T-cell aplasia, leading to fatal immunodeficiency. We recently identified the CD1a antigen as a safe target for CD1a+ cortical T-ALL (coT-ALL), a major subgroup of T-ALL, and we have developed a novel CD1a-specific CAR. Results generated from my previous ERC-funded work (INFANTLEUKEMIA nº646903 and IT4-BALL nº811220) have just been protected by a European Patent (EP19382104.8; CARTs for the treatment of CD1a+ cancer). Our intellectual property rights coupled to our internationally-endorsed top-tier scientific publication are a major strength of our proof-of-principle demonstration that CD1a-directed CAR T-cells constitute a unique immunotherapy approach for coT-ALL. We propose to consolidate final technical-biological improvements and GMP-grade manufacturing of our CD1a-directed CAR T-cells in compliance with the requirements of the Spanish Regulatory Agency of Medicines and Medical Devices for advanced adoptive cellular therapies (AEMPS). Data from this project will be added to the final Investigational Medicinal Product Dossier (IMPD) of the CARCD1a T-cells to be submitted to AEMPS for regulatory approval to launch a pan-European open Phase Ib clinical trial for relapse/refractory coT-ALL in early 2022, ensuring social and health value of this innovative immunotherapy.

Pablo Menéndez – Institut de Recerca contra la Leucèmia Josep Carreras (IJC)
PoC – 2021

GENETTA – Genomic Data-Fusion Platform for Omics-Driven Precision Medicine

This PoC project aims to pave the road to commercialize a comprehensive data analytics platform enabling data-driven biomedical innovation and precision medicine. The platform is specifically designed to efficiently fuse and mine heterogeneous omic data, including genomes, epigenomes, proteomes, metabolomes, patient clinical profiles, drugs and their chemical similarities, disease and other ontologies, and other relevant omic data. The goal of this development is to provide the most advanced software platform for fusion and analytics of numerous heterogeneous multi-scale omic data that takes advantage of novel non-negative matrix trifactorization (NMTF)-based and network mining algorithms, providing dramatic improvements in the number and type of fused data, quantity of data, computational efficiency and biomedical accuracy compared to the most advanced omic data analytics platforms currently existing. The main goal of the PoC is to close the gap between the research results of ERC Consolidator Grant, ICON-BIO, and the production of a commercial data analytics platform for the bio-pharmaceutical sector. In particular, the solution will target biopharma companies to embed the platform into their existing Data Science resources and enable effective and efficient application of the platform’s explainable AI methods (resulting from ICON-BIO) to optimize and guide their discovery processes. The result of this effort will be the achievement of a market-ready Data Analytics Platform.

Natasa Przulj – Barcelona Supercomputing Centre – Centre Nacional de Supercomputació (BSC-CNS)
PoC – 2020

ICCION – Indigenous Climate Change Impacts Observation Network

The Local Indicators of Climate Change Impacts project (771056-LICCI-ERC-2017-COG) explores the potential of Indigenous and local knowledge (ILK) to contribute to climate research, but only tangentially addresses the marginalized position faced by Indigenous Peoples and local communities (IPLC) to bring their knowledge and perspectives to climate change research and policy fora. This PoC will bring IPLC knowledge and perspectives to climate change research and policy fora by 1) engage with IPLC on the co-design of a digital Indigenous Climate Change Impacts Observation Network (ICCION) and 2) engaging with the Local Communities and Indigenous Peoples Platform (LCIPP) of the UNFCCC, which has the mandate to strengthen IPLC knowledge and efforts related to addressing and responding to climate change. ICCION holds social, political, and technological innovative potential. The creation of an Indigenous Climate Change Impacts Observation Network is an innovative response to the IPCC call for more ground level data, as it will bring expand the geographical and temporal coverage of data collection on local indicators of climate change impacts. Moreover, partnering with IPLC and international organizations constitutes an important social innovation, as these alliances might facilitate the process of establishing a continuous, iterative, and bidirectional dialogue that foster IPLC effective participation in climate change science-policy fora. Finally, ICCION innovates in developing technological solutions to address technical (i.e., low internet access) and social concerns (i.e., Indigenous data sovereignty) that are of particular relevance for IPLC, but which have often been neglected in other technological developments. The long-term establishment of the observation network proposed here will contribute to give IPLC a more relevant voice in global climate policy fora, not only by informing climate change impact research, but also making it more socially acceptable.

Victoria Reyes-García – Universitat Autòmona de Barcelona (UAB)
PoC – 2019

SENFIB – Novel senolytic drugs for the treatment of lung and kidney fibrosis

SENFIB aims to deliver new drugs for the treatment of fibrotic diseases. Nearly one quarter of the global population will be over the age of 65 by 2050. Populations over 65 suffer from multiple degenerative diseases including tissue fibrosis, estimated to account for upwards of 45% of all-cause mortality. Animal models have demonstrated that senescent cells are causative in many fibrotic diseases including lung (i.e. idiopathic pulmonary fibrosis, IPF), and chronic kidney disease (CKD). Senescent cells have experienced damage or stress and have permanently exited the cell cycle, yet remain viable and long-lived, generating a persistent, sterile inflammation. Selective elimination of senescent cells in animal models of IPF, CKD, and aging demonstrated improved organ function and viability. Senolytics, molecules that induce preferential killing of senescent cells while leaving healthy cells intact, have emerged as a promising approach for tackling age-associated diseases; this was named one of the “10 Breakthrough Technologies” of 2020 by the MIT Technology Review. Thus far, few senolytics have been identified; their mode of action is often unknown, some present serious toxicities, and none has yet been demonstrated to have therapeutic activity in clinical trials. We propose to launch a drug discovery program based on a prioritized novel genetic target for senolysis, which we have already validated as senolytic using a tool compound in an in vivo model of IPF. We will deliver a lead series of molecules with IPR that meet all typical drug requirements plus in vivo Proof-of-Concept data in different mouse models of IPF and CKD. The ultimate goal of this project is to develop candidates for translation into clinical use to ameliorate fibrotic diseases via the selective elimination of senescent cells.

Manuel Serrano – Institut de Recerca Biomèdica (IRB Barcelona)
PoC – 2020