ERC FUNDED PROJECTS

Organic Light Emitting Diodes (OLEDs) are attractive for use in high efficiency illumination and flexible displays. The current state of the art OLED materials use Ir or Pt based phosphorescent materials, which whilst achieving impressive efficiencies have significant cost, and supply issues associated with rare precious metals. Metal free OLEDs are preferable based on low relative cost and ease of fabrication but to date have not been competitive with Ir / Pt based OLEDs. This is because metal free OLEDs have relatively low efficiency as light emission is due to fluorescence inherently limiting the systems to 25% of excitons. A new approach has now enabled metal free OLEDs to break this efficiency barrier – using the phenomena of thermally activated delayed fluorescence (TADF). However, TADF emitters in the deep red / Near infra red (NIR) region of the spectra (desired for applications in optical communications, night vision devices and sensors) are rare and currently sub-optimal. ERC funded research led us to discover a new methodology for forming fused pi conjugated materials that possess desirable properties for OLEDs this includes small band gaps, excellent emission in the deep red and NIR-region of the spectra and good stability. Whilst these materials exhibit excellent solid state photoluminescence quantum yields for emitters in the deep red and NIR region of the spectra their performance in OLED devices was only moderate. This is due to the absence of TADF in the materials studied to date. This work program will modify our current materials to maintain the desirable properties but to incorporate moieties that switch on TADF. Materials will be selected based on calculations (of relative S1/T1 energies), synthesised and assessed for TADF (lifetimes / effect of O2 etc.), with best in class used to fabricate OLED devices. This will lead to increases in OLED device efficiency hopefully to a level that is commercially viable.

149 662 €

Start date: 2016-08-01, End date: 2018-01-31

Half of “late talkers”, infants who are not yet speaking by 2 years of age, will go on to develop language impairments. Currently, we have no reliable means of identifying these infants. Here we combine our developmental approach to phonology (psycholinguistic grain size theory), to the neural mechanisms underlying speech encoding (temporal sampling [TS] theory) and our work on the developmental importance of the speech amplitude envelope (AE) to open a new research front in the foundations of language acquisition. Recent adult research confirms our decade-long focus on the importance of sensitivity to AE ‘rise time’ in children’s language development, showing that rise times (‘auditory edges’) re-set the endogenous cortical oscillations that encode speech. Accordingly, we now apply our in-house state-of-the-art methods for measuring oscillatory rhythmic entrainment in children along with our recent theoretical and behavioural advances concerning AE processing to infant studies. Our core aim is to use the TS theoretical perspective and analysis methods to generate robust early neural and behavioural markers of phonological and morphological development: TS for infants. We have published the first-ever studies of oscillatory entrainment to speech rhythm by children and we have developed methods for technically-challenging EEG speech envelope reconstruction. We now apply these innovative methods to infant language learning and infant-directed speech. Using our cutting-edge EEG methods, we will deliver a novel and innovative road map for charting early language acquisition from a rhythmic entrainment perspective. Our recent 5-year study of rise time sensitivity in infants confirms the feasibility of a TS approach. As our focus is on prosody, syllable stress and syllable processing, our methods will apply across European languages.

2 614 275 €

Start date: 2016-09-01, End date: 2021-08-31

Back pain affects eight out of ten adults during their lifetime. It a huge economic burden on society, estimated to cost as much as 1-2% of gross national product in several European countries. Treatments for back pain have lower levels of success and are not as technologically mature as those for other musculoskeletal disorders such as hip and knee replacement. This application proposes to tackle one of the major barriers to the development of better surgical treatments for back pain. At present, new spinal devices are commonly assessed in isolation in the laboratory under standardised conditions that do not represent the variation across the patient population. Consequently many interventions have failed during clinical trials or have proved to have poor long term success rates. Using a combination of computational and experimental models, a new testing methodology will be developed that will enable the variation between patients to be simulated for the first time. This will enable spinal implants and therapies to be more robustly evaluated across a virtual patient population prior to clinical trial. The tools developed will be used in collaboration with clinicians and basic scientists to develop and, crucially, optimise new treatments that reduce back pain whilst preserving the unique functions of the spine. If successful, this approach could be translated to evaluate and optimise emerging minimally invasive treatments in other joints such as the hip and knee. Research in the spine could then, for the first time, lead rather than follow that undertaken in other branches of orthopaedics.

1 498 777 €

Start date: 2012-12-01, End date: 2018-11-30

The standard model of cosmology, the ɅCDM model, is remarkably successful at explaining a wide range of observations of our Universe. However, it is now being subjected to much more stringent tests than ever before, and recent large-scale structure (LSS) measurements appear to be in tension with its predictions. Is this tension signalling that new physics is required? For example, time-varying dark energy, or perhaps a modified theory of gravity? A contribution from massive neutrinos? Before coming to such bold conclusions we must be certain that all of the important systematic errors in the LSS tests have been accounted for. Presently, the largest source of systematic uncertainty is from the modelling of complicated astrophysical phenomena associated with galaxy formation. In particular, energetic feedback processes associated with star formation and black hole growth can heat and expel gas from collapsed structures and modify the large-scale distribution of matter. Furthermore, the LSS field is presently separated into many sub-fields (each using different models, that usually neglect feedback), preventing a coherent analysis. Cosmological hydrodynamical simulations (are the only method which) can follow all the relevant matter components and self-consistently capture the effects of feedback. I have been leading the development of large-scale simulations with physically-motivated prescriptions for feedback that are unrivalled in their ability to reproduce the observed properties of massive systems. With ERC support, I will build a team to exploit these developments, to produce a suite of simulations designed specifically for LSS cosmology applications with the effects of feedback realistically accounted for and which will allow us to unite the different LSS tests. My team and I will make the first self-consistent comparisons with the full range of LSS cosmology tests, and critically assess the evidence for physics beyond the standard model.

1 725 982 €

Start date: 2018-06-01, End date: 2023-05-31

"A major outstanding challenge for evolutionary biology is to explain how novel adaptations arise. We propose to test whether developmental plasticity initiates evolutionary change in morphological, behavioural and social traits, using laboratory experiments, fieldwork and comparative analyses. Using burying beetles Nicrophorus spp as our model experimental system, we shall: 1) Test whether variation in parental provisioning during development induces correlated phenotypic change in adult body size and a suite of life history traits; whether these phenotypic changes can be genetically accommodated under experimental evolution (the Baldwin Effect); and whether changes induced by experimental evolution mimic natural variation in adult body size and life history strategy among Nicrophorus species; 2) Test whether parental provisioning has a canalizing effect on the developmental environment, potentially storing up cryptic genetic variation which might then be released as random new phenotypes, if offspring are exposed to a new developmental environment; 3) Investigate whether developmental trade-offs, induced by under-provisioning from parents, provide the first step towards the evolution of a novel interspecific mutualism. Is a second species recruited in adulthood to carry out the function of a structure that was under-nourished during development? 4) Using comparative analyses of data from the literature on insects, frogs, birds and mammals, we shall test whether the evolution of parental provisioning in a given lineage is positively correlated with the number of species in the lineage. Our proposal is original in focusing on developmental plasticity induced by variation in parental provisioning. Given the diverse and numerous species that provision their young, including several whose genomes have now been sequenced, this potentially opens up a rich new area for future work on the developmental mechanisms underlying evolutionary innovations."

1 499 914 €

Start date: 2012-11-01, End date: 2017-10-31

Driven by public outrage at bank bailouts during the financial crisis, many governments have since then tried to rewrite the rules governing finance. Yet the anger provoked by the bailouts has not subsided. In Europe and in North America, citizen fury against bankers continues to structure battles over financial regulation. It also affects broader perceptions of fairness in the political system and feeds anti-elite populism. Scholars of political economy have chronicled the clashes between states and large banks, and scholars of political behaviour have noted the failings of governments to respond to the will of democratic majorities. No one has explored the feedback loops between policies regulating banks, the public anger towards banking elites, and media discussions of finance. BANK-LASH fills this gap, using a cutting-edge, high-risk research design comprising three work packages to link policy outcomes with public opinion and media coverage. BANK-LASH 1will collect the first cross-nationally comparable data on public attitudes towards finance, including a series of innovative survey experiments that assess how different media frames affect emotions and preferences. BANK-LASH 2 will use supervised machine learning to measure the overall media environment of these countries for the last decade, assessing how much different national media systems discuss finance and how different national media systems frame the discussion of banking regulation. BANK-LASH 3 links the micro-level study of attitudes and macro-level media coverage with episodes of policy intervention in each country in order to determine when democracies have imposed significant new regulation on their banks. By harnessing these different intellectual tools within a single study, BANK-LASH brings together the concerns of political economy, behavioral research and policy studies to untangle the relationship between banks, public policy, and anti-elite sentiment in the wake of the financial crisis.

2 454 198 €

Start date: 2018-09-01, End date: 2023-08-31

"Prostate cancer is the commonest solid cancer in men in the European Community. There is evidence for genetic predisposition to the development of prostate cancer and our group has found the largest number of such genetic variants described to date worldwide. The next challenge is to harness these discoveries to advance the clinical care of populations and prostate cancer patients to improve screening and target treatments. This proposal, BARCODE, aims to be ground-breaking in this area. BARCODE has two components (1) to profile a population in England using the current 77 genetic variant profile and compare screening outcomes with those from population based screening studies to determine if genetics can target screening more effectively in this disease by identifying prostate cancer that more often needs treatment and (2) genetically profiling men with prostate cancer in the uro-oncology clinic for a panel of genes which predict for worse outcome so that these men can be offered more intensive staging and treatment within clinical trials. This will use next generation sequencing technology using a barcoding system which we have developed to speed up throughput and reduce costs. The PI will spend 35% of her time on this project and she will not charge for her time spent on this grant as she is funded by The University of London UK. The research team at The Institute Of Cancer Research, London, UK is a multidisciplinary team which leads the field of genetic predisposition to prostate cancer and its clinical application and so is well placed to deliver on this research. This application will have a dramatic impact on other researchers as it is ground –breaking and state of the art in its application of genetic findings to public health and cancer care. It will therefore influence the work being undertaken in both these areas to integrate genetic profiling and gene panel analysis into population screening and cancer care respectively."

2 499 123 €

Start date: 2014-10-01, End date: 2019-09-30

The development of longer lasting, higher energy density and cheaper rechargeable batteries represents one of the major technological challenges of our society, batteries representing the limiting components in the shift from gasoline-powered to electric vehicles. They are also required to enable the use of more (typically intermittent) renewable energy, to balance demand with generation. This proposal seeks to develop and apply new NMR metrologies to determine the structure and dynamics of the multiple electrode-electrolyte interfaces and interphases that are present in these batteries, and how they evolve during battery cycling. New dynamic nuclear polarization (DNP) techniques will be exploited to extract structural information about the interface between the battery electrode and the passivating layers that grow on the electrode materials (the solid electrolyte interphase, SEI) and that are inherent to the stability of the batteries. The role of the SEI (and ceramic interfaces) in controlling lithium metal dendrite growth will be determined in liquid based and all solid state batteries. New DNP approaches will be developed that are compatible with the heterogeneous and reactive species that are present in conventional, all-solid state, Li-air and redox flow batteries. Method development will run in parallel with the use of DNP approaches to determine the structures of the various battery interfaces and interphases, testing the stability of conventional biradicals in these harsh oxidizing and reducing conditions, modifying the experimental approaches where appropriate. The final result will be a significantly improved understanding of the structures of these phases and how they evolve on cycling, coupled with strategies for designing improved SEI structures. The nature of the interface between a lithium metal dendrite and ceramic composite will be determined, providing much needed insight into how these (unwanted) dendrites grow in all solid state batteries. DNP approaches coupled with electron spin resonance will be use, where possible in situ, to determine the reaction mechanisms of organic molecules such as quinones in organic-based redox flow batteries in order to help prevent degradation of the electrochemically active species. This proposal involves NMR method development specifically designed to explore a variety of battery chemistries. Thus, this proposal is interdisciplinary, containing both a strong emphasis on materials characterization, electrochemistry and electronic structures of materials, interfaces and nanoparticles, and on analytical and physical chemistry. Some of the methodology will be applicable to other materials and systems including (for example) other electrochemical technologies such as fuel cells and solar fuels and the study of catalysts (to probe surface structure).

3 498 219 €

Start date: 2019-10-01, End date: 2024-09-30

This project aims to improve evidence-based decision-making. What makes it radical is that it plans to do this in situations (common for critical risk assessment problems) where there is little or even no data, and hence where traditional statistics cannot be used. To address this problem Bayesian analysis, which enables domain experts to supplement observed data with subjective probabilities, is normally used. As real-world problems typically involve multiple uncertain variables, Bayesian analysis is extended using a technique called Bayesian networks (BNs). But, despite many great benefits, BNs have been under-exploited, especially in areas where they offer the greatest potential for improvements (law, medicine and systems engineering). This is mainly because of widespread resistance to relying on subjective knowledge. To address this problem much current research assumes sufficient data are available to make the expert’s input minimal or even redundant; with such data it may be possible to ‘learn’ the underlying BN model. But this approach offers nothing when there is limited or no data. Even when ‘big’ data are available the resulting models may be superficially objective but fundamentally flawed as they fail to capture the underlying causal structure that only expert knowledge can provide. Our solution is to develop a method to systemize the way expert driven causal BN models can be built and used effectively either in the absence of data or as a means of determining what future data is really required. The method involves a new way of framing problems and extensions to BN theory, notation and tools. Working with relevant domain experts, along with cognitive psychologists, our methods will be developed and tested experimentally on real-world critical decision-problems in medicine, law, forensics, and transport. As the work complements current data-driven approaches, it will lead to improved BN modelling both when there is extensive data as well as none.

1 572 562 €

Start date: 2014-04-01, End date: 2018-03-31

"This project will develop a new framework for modeling economic agents having ""boundedly rational expectations"" (BRE). It is based on the concept of Bayesian networks (more generally, graphical models), borrowed from statistics and AI. In the framework's basic version, an agent is characterized by a directed acyclic graph (DAG) over the set of all relevant random variables. The DAG is the agent's ""type"" – it represents how he systematically distorts any objective probability distribution into a subjective belief. Technically, the distortion takes the form of the standard Bayesian-network factorization formula given by the agent's DAG. The agent's choice is modeled as a ""personal equilibrium"", because his subjective belief regarding the implications of his actions can vary with his own long-run behavior. The DAG representation unifies and simplifies existing models of BRE, subsuming them as special cases corresponding to distinct graphical representations. It captures hitherto-unmodeled fallacies such as reverse causation. The framework facilitates behavioral characterizations of general classes of models of BRE and expands their applicability. I will demonstrate this with applications to monetary policy, behavioral I.O., asset pricing, etc. I will extend the basic formalism to multi-agent environments, addressing issues beyond the reach of current models of BRE (e.g., formalizing the notion of ""high-order"" limited understanding of statistical regularities). Finally, I will seek a learning foundation for the graphical representation of BRE, in the sense that it will capture how the agent extrapolates his belief from a dataset (drawn from the objective distribution) containing ""missing values"", via some intuitive ""imputation method"". This part, too, borrows ideas from statistics and AI, further demonstrating the project's interdisciplinary nature."

1 379 288 €

Start date: 2016-07-01, End date: 2021-06-30

The production of antibodies against pathogens is an effective mechanism of protection against a wide range of infections. However, some pathogens evade antibody responses by rapidly changing their composition. Designing vaccines that elicit antibody responses against invariant parts of the pathogen is a rational strategy to combat existing and emerging pathogens. Production of antibodies is initiated by binding of B cell receptors (BCRs) to foreign antigens presented on the surfaces of antigen presenting cells. This binding induces B cell signalling and internalisation of the antigens for presentation to helper T cells. Although it is known that T cell help controls B cell expansion and differentiation into antibody-secreting and memory B cells, how the strength of antigen binding to the BCR regulates antigen internalisation remains poorly understood. As a result, the response and the affinity maturation of individual B cell clones are difficult to predict, posing a problem for the design of next-generation vaccines. My aim is to develop an understanding of the cellular mechanisms that underlie critical B cell activation steps. My laboratory has recently described that B cells use mechanical forces to extract antigens from antigen presenting cells. We hypothesise that application of mechanical forces tests BCR binding strength and thereby regulates B cell clonal selection during antibody affinity maturation and responses to pathogen evasion. We propose to test this hypothesis by (1) determining the magnitude and timing of the forces generated by B cells, and (2) determining the role of the mechanical properties of BCR-antigen bonds in affinity maturation and (3) in the development of broadly neutralising antibodies. We expect that the results of these studies will contribute to our understanding of the mechanisms that regulate the antibody repertoire in response to infections and have practical implications for the development of vaccines.

1 999 386 €

Start date: 2015-09-01, End date: 2020-08-31

The objective of the BEACON project is to (re-)introduce analog communications into the design of modern wireless networks. We argue that the extreme energy and latency constraints imposed by the emerging Internet of Everything (IoE) paradigm can only be met within a hybrid digital-analog communications framework. Current network architectures separate source and channel coding, orthogonalize users, and employ long block-length digital source and channel codes, which are either suboptimal or not applicable under the aforementioned constraints. BEACON questions these well-established design principles, and proposes to replace them with a hybrid digital-analog communications framework, which will meet the required energy and latency constraints while simplifying the encoding and decoding processes. BEACON pushes the performance of the IoE to its theoretical limits by i) exploiting signal correlations that are abundant in IoE applications, given the foreseen density of deployed sensing devices, ii) taking into account the limited and stochastic nature of energy availability due to, for example, energy harvesting capabilities, iii) using feedback resources to improve the end-to-end signal distortion, and iv) deriving novel converse results to identify fundamental performance benchmarks. The results of BEACON will not only shed light on the fundamental limits on the performance any coding scheme can achieve, but will also lead to the development of unconventional codes and communication protocols that can approach these limits, combining digital and analog communication techniques. The ultimate challenge for this project is to exploit the developed hybrid digital-analog networking theory for a complete overhaul of the physical layer design for emerging IoE applications, such as smart grids, tele-robotics and smart homes. For this purpose, a proof-of-concept implementation test-bed will also be built using software defined radios and sensor nodes.

1 496 350 €

Start date: 2016-10-01, End date: 2021-09-30

The majority of the globe's population carries a mobile phone, but with the increasing proliferation of smart phones and tablet-computers the tele-traffic is predicted to grow 1000-fold over the next decade, especially, when aiming for creating the impression of ubiquitous and flawless 'tele-presence' based on crisp, three-dimensional (3D) video with its sense of joy and wonder. For tele-presence to become a reality requires a further quantum-leap from the popular 3G/4G smart phones and tablet-computers. This project will create the link-level enabling techniques of this transformational quantum leap to immersive Giga-bit 3D video communications, relying on Optical Wireless (OW) hotspots and their ad hoc networking. As a result, the Beam-Me-Up project will contribute to job- and wealth-creation in numeorus ways, as exemplified by the often-quoted economic benefits of 3G/4G phones on businesses. From an environmental perspective, flawless tele-presence has the potential of eliminating millions of flights/trips and hence will considerably reduce CO2 emissions, whilst reducing the related business-costs as well as saving precious time for the work-force. However, the transfiguration of the voice-only phone into today's intelligent smart phone was facilitated by a 1000-fold transmission-rate increase, which would result in a proportionally increased power consumption, CO2 emissions and in a soaring energy-bill. Tele-presence based on crisp Avatar-style 3D video has even higher bitrates and energy consumption. These radically new high-rate 3D tele-presence services can no longer be accommodated in the severely congested Radio Frequency (RF) band. Hence the project will create a suite of new OW system components, operating in the visible-light domain and will conceive low-power, low-complexity OW solutions to enable immersive Giga-bit 3D wireless video communications over heterogeneous networks.

2 470 416 €

Start date: 2013-03-01, End date: 2018-02-28

Planets orbiting both stars of a binary system -circumbinary planets- are challenging our understanding about how planets assemble, and how their orbits subsequently evolve. Long confined to science-fiction, circumbinary planets were confirmed by the Kepler spacecraft, in one of its most spectacular, and impactful result. Despite Kepler’s insights, a lot remains unknown about these planets. Kepler also suffered from intractable biases that the BEBOP project will solve. BEBOP will revolutionise how we detect and study circumbinary planets. Conducting a Doppler survey, we will vastly improve the efficiency of circumbinary planet detection, and remove Kepler’s biases. BEBOP will construct a clearer picture of the circumbinary planet population, and free us from the inherent vagaries, and important costs of space-funding. Thanks to the Doppler method we will study dynamical effects unique to circumbinary planets, estimate their multiplicity, and compute their true occurrence rate. Circumbinary planets are essential objects. Binaries disturbe planet formation. Any similarity, and any difference between the population of circumbinary planets and planets orbiting single stars, will bring novel information about how planets are produced. In addition, circumbinary planets have unique orbital properties that boost their probability to experience transits. BEBOP’s detections will open the door to atmospheric studies of colder worlds than presently available. Based on already discovered systems, and on two successful proofs-of-concept, the BEBOP team will detect 15 circumbinary gas-giants, three times more than Kepler. BEBOP will provide an unambiguous measure of the efficiency of gas-giant formation in circumbinary environments. In addition the BEBOP project comes with an ambitious programme to combine three detection methods (Doppler, transits, and astrometry) in a holistic approach that will bolster investigations into circumbinary planets, and create a lasting legacy.

1 186 313 €

Start date: 2018-11-01, End date: 2023-10-31

Social interactions are multifaceted and subtle, yet we can almost instantaneously discern if two people are cooperating or competing, flirting or fighting, or helping or hindering each other. Surprisingly, the development and brain basis of this remarkable ability has remained largely unexplored. At the same time, understanding how we develop the ability to process and use social information from other people is widely recognized as a core challenge facing developmental cognitive neuroscience. The Becoming Social project meets this challenge by proposing the most complete investigation to date of the development of the behavioural and neurobiological systems that support complex social perception. To achieve this, we first systematically map how the social interactions we observe are coded in the brain by testing typical adults. Next, we investigate developmental change both behaviourally and neurally during a key stage in social development in typically developing children. Finally, we explore whether social interaction perception is clinically relevant by investigating it developmentally in autism spectrum disorder. The Becoming Social project is expected to lead to a novel conception of the neurocognitive architecture supporting the perception of social interactions. In addition, neuroimaging and behavioural tasks measured longitudinally during development will allow us to determine how individual differences in brain and behaviour are causally related to real-world social ability and social learning. The planned studies as well as those generated during the project will enable the Becoming Social team to become a world-leading group bridging social cognition, neuroscience and developmental psychology.

1 500 000 €

Start date: 2017-04-01, End date: 2022-03-31

The aim of the BEEHIVE project is to generate novel insight into HIV biology, evolution and epidemiology, leveraging next-generation high-throughput sequencing and bioinformatics to produce and analyse whole-genomes of viruses from approximately 3,000 European HIV-1 infected patients. These patients have known dates of infection spread over the last 25 years, good clinical follow up, and a wide range of clinical prognostic indicators and outcomes. The primary objective is to discover the viral genetic determinants of severity of infection and set-point viral load. This primary objective is high-risk & blue-skies: there is ample indirect evidence of polymorphisms that alter virulence, but they have never been identified, and it is not known how easy they are to discover. However, the project is also high-reward: it could lead to a substantial shift in the understanding of HIV disease. Technologically, the BEEHIVE project will deliver new approaches for undertaking whole genome association studies on RNA viruses, including delivering an innovative high-throughput bioinformatics pipeline for handling genetically diverse viral quasi-species data (with viral diversity both within and between infected patients). The project also includes secondary and tertiary objectives that address critical open questions in HIV epidemiology and evolution. The secondary objective is to use viral genetic sequences allied to mathematical epidemic models to better understand the resurgent European epidemic amongst high-risk groups, especially men who have sex with men. The aim will not just be to establish who is at risk of infection, which is known from conventional epidemiological approaches, but also to characterise the risk factors for onwards transmission of the virus. Tertiary objectives involve understanding the relationship between the genetic diversity within viral samples, indicative of on-going evolution or dual infections, to clinical outcomes.

2 499 739 €

Start date: 2014-04-01, End date: 2019-03-31

The Endoplasmic Reticulum (ER) membrane in all eukaryotic cells has an intricate protein network that facilitates protein biogene-sis and homeostasis. The molecular complexity and sophisticated regulation of this machinery favours study-ing it in its native microenvironment by novel approaches. Cryo-electron tomography (CET) allows 3D im-aging of membrane-associated complexes in their native surrounding. Computational analysis of many sub-tomograms depicting the same type of macromolecule, a technology I pioneered, provides subnanometer resolution insights into different conformations of native complexes. I propose to leverage CET of cellular and cell-free systems to reveal the molecular details of ER protein bio-genesis and homeostasis. In detail, I will study: (a) The structure of the ER translocon, the dynamic gateway for import of nascent proteins into the ER and their maturation. The largest component is the oligosaccharyl transferase complex. (b) Cotranslational ER import, N-glycosylation, chaperone-mediated stabilization and folding as well as oligomerization of established model substrate such a major histocompatibility complex (MHC) class I and II complexes. (c) The degradation of misfolded ER-residing proteins by the cytosolic 26S proteasome using cytomegalovirus-induced depletion of MHC class I as a model system. (d) The structural changes of the ER-bound translation machinery upon ER stress through IRE1-mediated degradation of mRNA that is specific for ER-targeted proteins. (e) The improved ‘in silico purification’ of different states of native macromolecules by maximum likelihood subtomogram classification and its application to a-d. This project will be the blueprint for a new approach to structural biology of membrane-associated processes. It will contribute to our mechanistic understanding of viral immune evasion and glycosylation disorders as well as numerous diseases involving chronic ER stress including diabetes and neurodegenerative diseases.

2 496 611 €

Start date: 2017-04-01, End date: 2022-03-31

"I will study questions of central microeconomic importance via interwoven theoretical, empirical, and experimental analyses, from a behavioural perspective combining standard methods with assumptions that better reflect evidence on behaviour and psychological insights. The contributions of behavioural economics have been widely recognized, but the benefits of its insights are far from fully realized. I propose four lines of inquiry that focus on how institutions interact with cognition and behaviour, chosen for their potential to reshape our understanding of important questions and their synergies across lines. The first line will study nonparametric identification and estimation of reference-dependent versions of the standard microeconomic model of consumer demand or labour supply, the subject of hundreds of empirical studies and perhaps the single most important model in microeconomics. It will allow such studies to consider relevant behavioural factors without imposing structural assumptions as in previous work. The second line will analyze history-dependent learning in financial crises theoretically and experimentally, with the goal of quantifying how market structure influences the likelihood of a crisis. The third line will study strategic thinking experimentally, using a powerful new design that links subjects’ searches for hidden payoff information (“eye-movements”) much more directly to thinking. The fourth line will significantly advance Myerson and Satterthwaite’s analyses of optimal design of bargaining rules and auctions, which first went beyond the analysis of given institutions to study what is possible by designing new institutions, replacing their equilibrium assumption with a nonequilibrium model that is well supported by experiments. The synergies among these four lines’ theoretical analyses, empirical methods, and data analyses will accelerate progress on each line well beyond what would be possible in a piecemeal approach."

1 985 373 €

Start date: 2014-04-01, End date: 2019-03-31

OPPSEXRIGHTS will be the first large-scale, transnational study to consider the effects of recent Sexual and Gender Rights and Equalities (SGRE) on those who oppose them, by exploring opponents’ experiences of the transformation of everyday spaces. It will work beyond contemporary polarisations, creating new possibilities for social transformation. This cutting-edge research engages with the dramatically altered social and political landscapes in the late 20th and early 21st Century created through the development of lesbian, gay, bisexual, and trans, and women’s rights. Recent reactionary politics highlight the pressing need to understand the position of those who experience these new social orders as a loss. The backlash to SGRE has coalesced into various resistances that are tangibly different to the classic vilification of homosexuality, or those that are anti-woman. Some who oppose SGRE have found themselves the subject of public critique; in the workplace, their jobs threatened, while at home, engagements with schools can cause family conflicts. This is particularly visible in the case studies of Ireland, UK and Canada because of SGRE. A largescale transnational systematic database will be created using low risk (media and organisational discourses; participant observation at oppositional events) and higher risk (online data collection and interviews) methods. Experimenting with social transformation, OPPSEXRIGHTS will work to build bridges between ‘enemies’, including families and communities, through innovative discussion and arts-based workshops. This ambitious project has the potential to create tangible solutions that tackle contemporary societal issues, which are founded in polarisations that are seemingly insurmountable.

1 988 652 €

Start date: 2019-10-01, End date: 2024-09-30

The present proposal is concerned with the analysis of the Einstein equations of general relativity, a non-linear system of geometric partial differential equations describing phenomena from the bending of light to the dynamics of black holes. The theory has recently been confirmed in a spectacular fashion with the detection of gravitational waves. The main objective of the proposal is to consolidate my research group based at Imperial College by developing novel mathematical techniques that will fundamentally advance our understanding of the Einstein equations. Here the proposal builds on mathematical progress in the last decade resulting from achievements in the fields of partial differential equations, differential geometry, microlocal analysis and theoretical physics. The Black Hole Stability Problem A major open problem in general relativity is to prove the non-linear stability of the Kerr family of black hole solutions. Recent advances in the problem of linear stability made by the PI and collaborators open the door to finally address a complete resolution of the stability problem. In this proposal we will describe what non-linear techniques will need to be developed in addition to achieve this goal. A successful resolution of this program would conclude an almost 50-year-old problem. The Analysis of asymptotically anti-de Sitter (aAdS) spacetimes We propose to prove the stability of pure AdS if so-called dissipative boundary conditions are imposed at the boundary. This result would align with the well-known stability results for the other maximally-symmetric solutions of the Einstein equations, Minkowski space and de Sitter space. As a second -- related -- theme we propose to formulate and prove a unique continuation principle for the full non-linear Einstein equations on aAdS spacetimes. This goal will be achieved by advancing techniques that have recently been developed by the PI and collaborators for non-linear wave equations on aAdS spacetimes.

1 999 755 €

Start date: 2018-11-01, End date: 2023-10-31

This project will investigate the interface between the study of the bible and the study of antiquity in the nineteenth century. These two areas -- the bible and classics -- are central to the intellectual world of the 19th century, a source of knowledge, contention, and authority both as discrete topics, and, more importantly, in relation to and in competition with one another. It is impossible to understand Victorian society without appreciating the intellectual, social and institutional force of these concerns with the past. Yet modern disciplinary formation has not only separated them in the academy, but also marginalized both subject areas -- which has deeply attenuated comprehension of this foundational era. Our project will bring together scholars working on a range of fields including classics, history of education, cultural history, art history, literary history to bring back into view a fundamental but deeply misunderstood and underexplored aspect of the nineteenth century, which continues to have a significant impact on the contemporary world.

2 497 046 €

Start date: 2012-06-01, End date: 2017-05-31

As datasets grow ever larger in scale, complexity and variety, there is an increasing need for powerful machine learning and statistical techniques that are capable of learning from such data. Bayesian nonparametrics is a promising approach to data analysis that is increasingly popular in machine learning and statistics. Bayesian nonparametric models are highly flexible models with infinite-dimensional parameter spaces that can be used to directly parameterise and learn about functions, densities, conditional distributions etc, and have been successfully applied to regression, survival analysis, language modelling, time series analysis, and visual scene analysis among others. However, to successfully use Bayesian nonparametric models to analyse the high-dimensional and structured datasets now commonly encountered in the age of Big Data, we will have to overcome a number of challenges. Namely, we need to develop Bayesian nonparametric models that can learn rich representations from structured data, and we need computational methodologies that can scale effectively to the large and complex models of the future. We will ground our developments in relevant applications, particularly to natural language processing (learning distributed representations for language modelling and compositional semantics) and genetics (modelling genetic variations arising from population, genealogical and spatial structures).

1 918 092 €

Start date: 2014-05-01, End date: 2019-04-30

"We aim to establish a world-leading research capability in Europe for advancing novel models of asynchronous computation based upon principles inspired by brain function. This work will accelerate progress towards an understanding of how the potential of brain-inspired many-core architectures may be harnessed. The results will include new brain-inspired models of asynchronous computation and new brain- inspired approaches to fault-tolerance and reliability in complex computer systems. Many-core processors are now established as the way forward for computing from embedded systems to supercomputers. An emerging problem with leading-edge silicon technology is a reduction in the yield and reliability of modern processors due to high variability in the manufacture of the components and interconnect as transistor geometries shrink towards atomic scales. We are faced with the longstanding problem of how to make use of a potentially large array of parallel processors, but with the new constraint that the individual elements are the system are inherently unreliable. The human brain remains as one of the great frontiers of science – how does this organ upon which we all depend so critically actually do its job? A great deal is known about the underlying technology – the neuron – and we can observe large-scale brain activity through techniques such as magnetic resonance imaging, but this knowledge barely starts to tell us how the brain works. Something is happening at the intermediate levels of processing that we have yet to begin to understand, but the essence of the brain's massively-parallel information processing capabilities and robustness to component failure lies in these intermediate levels. These two issues draws us towards two high-level research questions: • Can our growing understanding of brain function point the way to more efficient parallel, fault-tolerant computing? • Can massively parallel computing resources accelerate our understanding of brain function"

2 399 761 €

Start date: 2013-03-01, End date: 2018-02-28

Amine containing compounds are ubiquitous in everyday life and find applications ranging from polymers to pharmaceuticals. The vast majority of amines are synthetic and manufactured on large scale which creates waste as well as requiring high temperatures and pressures. The increasing availability of biocatalysts, together with an understanding of how they can be used in organic synthesis (biocatalytic retrosynthesis), has stimulated chemists to consider new ways of making target molecules. In this context, the iterative construction of C-N bonds via biocatalytic hydrogen borrowing represents a powerful and unexplored way to synthesise a wide range of target amine molecules in an efficient manner. Hydrogen borrowing involves telescoping redox neutral reactions together using only catalytic amounts of hydrogen. In this project we will engineer the three key target biocatalysts (reductive aminase, amine dehydrogenase, alcohol dehydrogenase) required for biocatalytic hydrogen borrowing such that they possess the required regio-, chemo- and stereo-selectivity for practical application. Recently discovered reductive aminases (RedAms) and amine dehydrogenases (AmDHs) will be engineered for enantioselective coupling of alcohols (1o, 2o) with ammonia/amines (1o, 2o, 3o) under redox neutral conditions. Alcohol dehydrogenases will be engineered for low enantioselectivity. Hydrogen borrowing requires mutually compatible cofactors shared by two enzymes and in some cases will require redesign of cofactor specificity. Thereafter we shall develop conditions for the combined use of these biocatalysts under hydrogen borrowing conditions (catalytic NADH, NADPH), to enable the conversion of simple and sustainable feedstocks (alcohols) into amines using ammonia as the nitrogen source. The main deliverables of BIO-H-BORROW will be a set of novel engineered biocatalysts together with redox neutral cascades for the synthesis of amine products from inexpensive and renewable precursors.

2 337 548 €

Start date: 2017-06-01, End date: 2022-05-31

Meta-materials, best known for their extraordinary properties (e.g. negative stiffness), are halfway from both materials and structures: their unusual properties are direct results of their complex 3D structures. This project introduces a new class of meta-materials called meta-biomaterials. Meta-biomaterials go beyond meta-materials by adding an extra dimension to the complex 3D structure, i.e. complex and precisely controlled surface nano-patterns. The 3D structure gives rise to unprecedented or rare combination of mechanical (e.g. stiffness), mass transport (e.g. permeability, diffusivity), and biological (e.g. tissue regeneration rate) properties. Those properties optimize the distribution of mechanical loads and the transport of nutrients and oxygen while providing geometrical shapes preferable for tissue regeneration (e.g. higher curvatures). Surface nano-patterns communicate with (stem) cells, control their differentiation behavior, and enhance tissue regeneration. There is one important problem: meta-biomaterials cannot be manufactured with current technology. 3D printing can create complex shapes while nanolithography creates complex surface nano-patterns down to a few nanometers but only on flat surfaces. There is, however, no way of combining complex shapes with complex surface nano-patterns. The groundbreaking nature of this project is in solving that deadlock using the Origami concept (the ancient Japanese art of paper folding). In this approach, I first decorate flat 3D-printed sheets with nano-patterns. Then, I apply Origami techniques to fold the decorated flat sheet and create complex 3D shapes. The sheet knows how to self-fold to the desired structure when subjected to compression, owing to pre-designed joints, crease patterns, and thickness/material distributions that control its mechanical instability. I will demonstrate the added value of meta-biomaterials in improving bone tissue regeneration using in vitro cell culture assays and animal models

1 499 600 €

Start date: 2016-02-01, End date: 2021-01-31

Biomechanical interactions between cells and their environment are essential in almost any biological process, from embryonic development to organ function to diseases. Hence, biomechanical interactions are crucial for health and disease. Examples are hydrodynamic interactions through fluid flow, and forces acting directly on cells. Existing methods to analyze and understand these interactions are limited however, since they do not offer the required combination of precisely controlled flow and accurate applying and sensing of forces. Also, they often lack a physiological environment. A breakthrough in biomechanical analysis is therefore highly needed. We will realize a novel microfluidic platform for biomechanical analysis with unprecedented possibilities of controlling fluid flow and applying and sensing time-dependent forces at subcellular scales in controlled environments. The platform will be uniquely based on bio-inspired magnetic artificial cilia, rather than on conventional microfluidic valves and pumps. Cilia are microscopic hairs ubiquitously present in nature, acting both as actuators and sensors, essential for swimming of microorganisms, transport of dirt out of our airways, and sensing of sound, i.e. they exactly fulfill functions needed in biomechanical analysis. We will develop novel materials and fabrication methods to realize microscopic polymeric artificial cilia, and integrate these in microfluidic devices. Magnetic actuation and optical readout systems complete the platform. We will apply the novel platform to address three fundamental and unresolved biomechanical questions: 1. How do hydrodynamic interactions with actuated cilia steer cellular and particle transport? 2. How do local and dynamic mechanical forces on cells fundamentally influence their motility and differentiation? 3. How do hydrodynamic interactions between cilia steer embryonic development? This unique platform will enable to address many other future biomechanical questions.

3 083 625 €

Start date: 2019-10-01, End date: 2024-09-30

Personalized medicine is a medical model that proposes the customization of healthcare, with decisions and practices being tailored to the individual patient by use of patient-specific information and/or application of patient-specific cell-based therapies. BioBlood aims to deliver personalised healthcare through a “step change” in the clinical field of haemato-oncology. BioBlood represents an engineered bio-inspired integrated experimental/modelling platform for normal and abnormal haematopoiesis that receives disease & patient input (patient primary cells & patient/disease-specific data) and will produce cellular (red blood cell product) and drug (optimal drug treatment) therapies as its output. Blood supply to meet demand is the primary challenge for Blood Banks and requires significant resources to avoid shortages and ensure safety. An alternative, practical and cost-effective solution to conventional donated blood is essential to reduce patient morbidity and mortality, stabilise and guarantee the donor supply, limit multiple donor exposures, reduce risk of infection of known or as yet unidentified pathogens, and ensure a robust and safe turn-around for blood supply management. BioBlood aims to meet this challenge by developing a novel in vitro platform for the mass production of RBCs for clinical use. More than £32b/year is spent to develop and bring new drugs to market, which takes 14 years. Most patients diagnosed with leukaemias are unable to tolerate treatment and would benefit from novel agents. There is a need to optimise current treatment schedules for cancers such as AML to limit toxicities and improve clinical trial pathways for new drugs to enable personalised healthcare. BioBlood’s in vitro & in silico platform would be a powerful tool to tailor treatments in a patient- and leukaemia-specific chemotherapy schedule by considering the level of toxicity to the specific individual and treatment efficiency for the specific leukaemia a priori.

2 498 903 €

Start date: 2014-01-01, End date: 2018-12-31

Myocardial infarction is responsible for nearly 40% of the mortality in the western world and is mainly triggered by rupture of vulnerable atherosclerotic plaques in the coronary arteries. Biomechanical parameters play a major role in the generation and rupture of vulnerable plaques. I was the first to show the relationship between shear stress – one of the biomechanical parameters - and plaque formation in human coronary arteries in vivo. This accomplishment was achieved by the development of a new 3D reconstruction technique for (human) coronary arteries in vivo. This reconstruction technique allowed assessment of shear stress by computational fluid dynamics and thereby opened new avenues for serial studies on the role of biomechanical parameters in cardiovascular disease. However, these reconstructions lack information on the vessel wall composition, which is essential for stress computations in the vessel wall. Recent developments in intravascular image technologies allow visualization of one or more of the different plaque components. Therefore, advances in image fusion are required to merge the different plaque components into one single 3D vulnerable plaque reconstruction. I will go beyond the state-of-the art in image based modeling by developing novel technology to 3D reconstruct coronary lumen and vessel wall, including plaque composition and assess biomechanical tissue properties allowing for full biomechanical characterization (shear stress and wall stress) of the coronary plaque. The developed technology will be applied to study 1) vulnerable plaque progression, destabilization and rupture, to improve identification of risk on myocardial infarction and 2) predicting treatment outcome of stent implantation by simulating stent deployment, thereby opening a whole new direction in cardiovascular research.

1 877 000 €

Start date: 2013-05-01, End date: 2019-04-30

Programmable biomolecular circuits have received increasing attention in recent years as the scope of chemistry expands from the synthesis of individual molecules to the construction of chemical networks that can perform sophisticated functions such as logic operations and feedback control. Rationally engineered biomolecular circuits that robustly execute higher-order spatiotemporal behaviours typically associated with intracellular regulatory functions present a unique and uncharted platform to systematically explore the molecular logic and physical design principles of the cell. The experience gained by in-vitro construction of artificial cells displaying advanced system-level functions deepens our understanding of regulatory networks in living cells and allows theoretical assumptions and models to be refined in a controlled setting. This proposal combines elements from systems chemistry, in-vitro synthetic biology and micro-engineering and explores generic strategies to investigate the molecular logic of biology’s regulatory circuits by applying a physical chemistry-driven bottom-up approach. Progress in this field requires 1) proof-of-principle systems where in-vitro biomolecular circuits are designed to emulate characteristic system-level functions of regulatory circuits in living cells and 2) novel experimental tools to operate biochemical networks under out-of-equilibrium conditions. Here, a comprehensive research program is proposed that addresses these challenges by engineering three biochemical model systems that display elementary signal transduction and information processing capabilities. In addition, an open microfluidic droplet reactor is developed that will allow, for the first time, high-throughput analysis of biomolecular circuits encapsulated in water-in-oil droplets. An integral part of the research program is to combine the computational design of in-vitro circuits with novel biochemistry and innovative micro-engineering tools.

1 887 180 €

Start date: 2016-08-01, End date: 2021-07-31

Heterogeneous biomolecular mechanisms at the surface of cellular membranes are often fundamental to generate function and dysfunction in living systems. These processes are governed by transient and dynamical macromolecular interactions that pose tremendous challenges to current analytical tools, as the majority of these methods perform best in the study of well-defined and poorly dynamical systems. This proposal aims at a radical innovation in the characterisation of complex processes that are dominated by structural order and disorder, including those occurring at the surface of biological membranes such as cellular signalling, the assembly of molecular machinery, or the regulation vesicular trafficking. I outline a programme to realise a vision where the combination of experiments and theory can delineate a new analytical platform to study complex biochemical mechanisms at a multiscale level, and to elucidate their role in physiological and pathological contexts. To achieve this ambitious goal, my research team will develop tools based on the combination of nuclear magnetic resonance (NMR) spectroscopy and molecular simulations, which will enable probing the structure, dynamics, thermodynamics and kinetics of complex protein-protein and protein-membrane interactions occurring at the surface of cellular membranes. The ability to advance both the experimental and theoretical sides, and their combination, is fundamental to define the next generation of methods to achieve our transformative aims. We will provide evidence of the innovative nature of the proposed multiscale approach by addressing some of the great questions in neuroscience and elucidate the details of how functional and aberrant biological complexity is achieved via the fine tuning between structural order and disorder at the neuronal synapse.

1 999 945 €

Start date: 2019-06-01, End date: 2024-05-31

The dielectric properties of biological tissues are of fundamental importance to the understanding of the interaction of electromagnetic fields with the human body. These properties are used to determine the safety of electronic devices, and in the design, development and refinement of electromagnetic medical imaging and therapeutic devices. Many historical studies have aimed to establish the dielectric properties of a broad range of tissues. A growing number of recent studies have sought to more accurately estimate these dielectric properties by standardising measurement procedures, and in some cases, measuring the dielectric properties in-vivo. However, these studies have often produced results in direct conflict with historical studies, casting doubt on the accuracy of the currently utilised dielectric properties. At best, this uncertainty could significantly delay the development of electromagnetic imaging or therapeutic medical devices. At worst, the health dangers of electromagnetic radiation could be under-estimated. The applicant will embark upon frontier research to develop improved methods and standards for the measurement of the dielectric properties of biological tissue. The research programme will accelerate the design and development of electromagnetic imaging and therapeutic devices, at a time when the technology is gaining significant momentum. The primary objective of the research is to develop a deep understanding of the fundamental factors which contribute to errors in dielectric property measurement. These factors will include in-vivo/ex-vivo measurements and dielectric measurement method used, amongst many others. Secondly, a new open-access repository of dielectric measurements will be created based on a greatly enhanced understanding of the mechanisms underlying dielectric property measurement. Finally, new electromagnetic-based imaging and therapeutic medical devices will be investigated, based on the solid foundation of dielectric data.

1 499 329 €

Start date: 2015-10-01, End date: 2020-09-30

Bioinorganic chemistry is a rapidly expanding area of research, but the potential for the therapeutic application of metal complexes is highly underdeveloped. The basic principles required to guide the development of metal-containing therapeutic agents are lacking, despite the unique therapeutic opportunities which they offer. It is the goal of the proposed research to establish basic principles of medicinal coordination chemistry of metals that will allow the rational screening of future metallopharmaceuticals. We propose to utilize the power of inorganic chemistry to provide new knowledge of and new approaches for intervention in biological systems. This will be based on improved understanding of reactions of metal complexes under physiological conditions, on improving the specificity of their interactions, and gaining control over the potential toxicity of synthetic metal complexes. The research programme is highly interdisciplinary involving chemistry, physics, biology and pharmacology, with potential for the discovery of truly novel medicines, especially for the treatment of diseases and conditions which are currently intractable, such as cancer. The challenging and ambitious goals of the present work involve transition metal complexes with novel chemical and biochemical mechanisms of action. They will contain novel features which allow them (i) to be selectively activated by light in cells, or (ii) to be activated by a structural transition, or (ii) exhibit catalytic activity in cells. This ground-breaking research potentially has a very high impact and is based on recent discoveries in the applicant s laboratory. A feature of the programme is the use of state-of-the-art-and-beyond methodology to advance knowledge of medicinal metal coordination chemistry.

1 565 397 €

Start date: 2010-07-01, End date: 2015-12-31

A range of new medical therapies and diagnostics based on magnetic nanomaterials have recently been proposed. These include cancer therapies, stem cell therapies, microfluidic diagnostic devices and immunoassays. However, very few biotechnology magnetic nanomaterials are currently available commercially; most investigators fabricate their own. This is a serious limitation to the development of this emerging area within nanomedicine. This proposal aims to transfer a number of magnetic nanomaterials from the University physics laboratory where they were developed as part of an ERC AdG grant into an existing small company where they can then be made available to researchers across the world on a commercial basis.

149 997 €

Start date: 2017-12-01, End date: 2019-05-31

In this BioMechMeniscus project we will develop a workflow for optimal placement of a novel meniscus implant. The medial meniscus implant (named ‘Trammpolin’) has been developed using methods developed during the BioMechTools project such as 1) principle component analyses based on MRI-segmented image to assess the anatomical shape of the meniscus, 2) assessing sensitivity of cartilage stresses and implant strains on size and design-parameters using finite element techniques and 3) utilizing load-predictions from our award-winning musculoskeletal models. All data shows that the biomechanical behaviour of Trammpolin in the knee will be sensitive to appropriate sizing and positioning within the knee. Therefore, this BioMechMeniscus project focuses on developing a surgeon-friendly platform to pre-plan the size and position and to execute the surgery as accurately as possible. The software will automatically perform MRI-segmentation of the tibia, femur and meniscus insertion sites. Subsequently, the best meniscus implant size and position (leading to the lowest cartilage stress and acceptable implant strains) is proposed by the program. The surgeon can adapt the proposal and gets feedback about the expected changes in biomechanical performance. After the pre-plan is accepted a patient-specific arthroscopic surgical guide is 3-D printed which will be used as an aiming device for an external (standard) surgical guide for fixation of the horns. The project is subdivided in four Tasks and will last for 18 months. An experienced team will supervise a post-doc during the various activities. A project scheme is made and a risk and contingency plan is defined. A detailed competitor and commercial analysis has been made and we are convinced that with the BioMechMeniscus project we have a unique opportunity to bring a novel implant to the market and support it with a distinct pre-planning and surgical assistance tool to optimize clinical performance.

150 000 €

Start date: 2017-11-01, End date: 2019-04-30

This ERC-StG proposal, BIOMOF, outlines a dual strategy for the growth and processing of porous metal-organic framework (MOF) materials, inspired by the interfacial interactions that characterise highly controlled biomineralisation processes. The aim is to prepare MOF (bio)-composite materials of hierarchical structure and multi-modal functionality to address key societal challenges in healthcare, catalysis and energy. In order for MOFs to reach their full potential, a transformative approach to their growth, and in particular their processability, is required since the insoluble macroscopic micron-sized crystals resulting from conventional syntheses are unsuitable for many applications. The BIOMOF project defines chemically flexible routes to MOFs under mild conditions, where the added value with respect to wide-ranging experimental procedures for the growth and processing of crystalline controllably nanoscale MOF materials with tunable structure and functionality that display significant porosity for wide-ranging applications is extremely high. Theme 1 exploits protein vesicles and abundant biopolymer matrices for the confined growth of soluble nanoscale MOFs for high-end biomedical applications such as cell imaging and targeted drug delivery, whereas theme 2 focuses on the cost-effective preparation of hierarchically porous MOF composites over several length scales, of relevance to bulk industrial applications such as sustainable catalysis, separations and gas-storage. This diverse yet complementary range of applications arising simply from the way the MOF is processed, coupled with the versatile structural and physical properties of MOFs themselves indicates strongly that the BIOMOF concept is a powerful convergent new approach to applied materials chemistry.

1 492 970 €

Start date: 2010-11-01, End date: 2015-10-31

The BioMusical Instrument project will create a product prototype of a wearable digital musical instrument based on biosignals from the performer’s muscles. It will allow musicians to perform electronic sounds from bodily gestures. Muscle tension will be sensed by innovative new electromyogram sensing hardware packaged in an ergonomic housing and coupled to wireless communication. Sophisticated machine learning methods developed in the ERC MetaGesture Music and H2020 Rapid-Mix projects will track musician gesture and create meaningful relationships with computer-based synthesized sound. The BioMusical Instrument will be marketed to three distinct application areas: First, it will enable “hands-free” performance of electronic music. Second, the visualization of body states will make it a useful training tool in traditional musical instrument pedagogy. Finally, the sonification of physiological signals will allow the instrument to be used in the health sector in physical rehabilitation exercises. The BioMusical Instrument will be the first product to combine EMG sensing, machine learning, and advanced audio signal processing. We have identified partners in the biomedical hardware field, the music technology industry, and rehabilitation research with whom we will benchmark and evaluate the product prototype.

149 901 €

Start date: 2018-05-01, End date: 2019-10-31

Genetic sequences have had an enormous impact on our understanding of biology. The expectation is that biological network data will have a similar impact. However, progress is hindered by a lack of sophisticated graph theoretic tools that will mine these large networked datasets. In recent breakthrough work at the boundary of computer science and biology supported by my USA NSF CAREER award, I developed sensitive network analysis, comparison and embedding tools which demonstrated that protein-protein interaction networks of eukaryotes are best modeled by geometric graphs. Also, they established phenotypically validated, unprecedented link between network topology and biological function and disease. Now I propose to substantially extend these preliminary results and design sensitive and robust network alignment methods that will lead to uncovering unknown biology and evolutionary relationships. The potential ground-breaking impact of such network alignment tools could be parallel to the impact the BLAST family of sequence alignment tools that have revolutionized our understanding of biological systems and therapeutics. Furthermore, I propose to develop additional sophisticated graph theoretic techniques to mine network data and hence complement biological information that can be extracted from sequence. I propose to exploit these new techniques for biological applications in collaboration with experimentalists at Imperial College London: 1. aligning biological networks of species whose genomes are closely related, but that have very different phenotypes, in order to uncover systems-level factors that contribute to pronounced differences; 2. compare and contrast stress response pathways and metabolic pathways in bacteria in a unified systems-level framework and exploit the findings for: (a) bioengineering of micro-organisms for industrial applications (production of bio-fuels, bioremediation, production of biopolymers); (b) biomedical applications.

1 638 175 €

Start date: 2012-01-01, End date: 2017-12-31

Bio-medical innovation makes a substantial contribution to Western societies and economies. But leading research organisations in the West are increasingly reliant on clinical research conducted beyond the West. Such initiatives are challenged by uncertainties about research quality and therapeutic practices in Asian countries. These only partly justified uncertainties are augmented by unfamiliar conditions. This study examines how to create responsible innovation in the life sciences by looking for ways to overcome existing obstacles to safe, just and ethical international science collaborations. Building on observations of scientists, managers and patients and supported by Asian language expertise, biology background, and experience with science and technology policy-making, we examine the roles of regional differences and inequalities in the networks used for patient recruitment and international research agreements. Profit-motivated networks in the life sciences also occur underground and at an informal, unregulated level, which we call bionetworking. Bionetworking is a social entrepreneurial activity involving biomedical research, healthcare and patient networks that are maintained by taking advantage of regionally differences in levels of science and technology, healthcare, education and regulatory regimes. Using novel social-science methods, the project studies two main themes. Theme 1 examines patient recruitment networks for experimental stem cell therapies and cooperation between research and health institutions involving exchanges of patients against other resources. Theme 2 maps and analyses exchanges of biomaterials of human derivation, and forms of ‘ownership’ rights, benefits and burdens associated with their donation, possession, maintenance, and application. Integral analysis of the project nodes incorporates an analysis of public health policy and patient preference in relation to Responsible innovation, Good governance and Global assemblages.

1 497 711 €

Start date: 2012-02-01, End date: 2017-01-31

This research project investigates the dynamics of private and public property in contemporary biomedical research. It will develop an analytical framework combining insights from science and technology studies, economic sociology, and legal and political philosophy, and pursues a social scientific investigation of the evolution of intellectual property rights in three fields of bioscientific research: 1) the use of transgenic research mice; 2) the legal status of totipotent and pluripotent stem cell lines; and 3) modes of collaboration for research and development on neglected diseases. These three domains, and their attendant modes of appropriation, will be compared across three general research themes: a) the production of public scientific goods; b) categories of appropriation; and c) the moral economy of research. The project rests on close observation of research practices in these three domains. The BioProperty research programme will track the trajectories of property rights and property objects in each of the three fields of biomedical research.

887 602 €

Start date: 2011-03-01, End date: 2014-12-31

The core intellectual aim of BIOSEC is to explore whether concerns about biodiversity protection and global security are becoming integrated, and if so, in what ways. It will do so via building new theoretical approaches for political ecology. Achim Steiner, UN Under-Secretary General and Executive Director of UNEP recently stated ‘the scale and role of wildlife and forest crime in threat finance calls for much wider policy attention’. The argument that wildlife trafficking constitutes a significant source of ‘threat finance’ takes two forms: first as a lucrative business for organised crime networks in Europe and Asia, and second as a source of finance for militias and terrorist networks, most notably Al Shabaab, Lord’s Resistance Army and Janjaweed. BIOSEC is a four year project designed to lead debates on these emerging challenges. It will build pioneering theoretical approaches and generate new empirical data. BIOSEC takes a fully integrated approach: it will produce a better conceptual understanding of the role of illegal wildlife trade in generating threat finance; it will examine the links between source and end user countries for wildlife products; and it will investigate and analyse the emerging responses of NGOs, government agencies and international organisations to these challenges. BIOSEC goes beyond the ‘state-of-the art’ because biodiversity protection and global security currently inhabit distinctive intellectual ‘silos’; however, they need to be analysed via an interdisciplinary research agenda that cuts across human geography, politics and international relations, criminology and conservation biology. This research is timely because in the last two years, the idea that the illegal wildlife trade constitutes a major security threat has become more prevalent in academic and policy circles, yet it is an area that is under researched and poorly understood. These recent shifts demand urgent conceptual and empirical interrogation.

1 822 729 €

Start date: 2016-09-01, End date: 2020-08-31

BioStealth production of implant coatings provides an exciting business opportunity. BioStealth offers unique advantages of societal and economic importance, such as public health and sick leave. Biocompatible materials, i.e. materials with proper cell response upon implantation, are attractive for restoring body function. Conventional implant coating methods lack in quality and therefore the majority, if not all, bio-coatings fail in proper interaction with host tissue, either caused by absence of biological triggers, biofouling or unwanted chemistry. This lack of proper interaction occurs fast upon implantation and disturbs specific cell interaction, eventually causing infections. Mostly, patients need rehospitalization which increase health care costs. BioStealth produces easy and cheap implant coatings by dipping or spraying lipids. BioStealth lipid coatings are air-stable and suitable for in-vivo use. BioStealth can be applied to FDA approved implant materials without changing the mechanical properties, which is key for tissue engineering and reconstructive medicine. BioStealth coatings have a tunable composition which makes them an ideal coating to improve interactions with cells. These factors greatly enhance application potential. Non-fouling lipids were suggested before, but as hydrogels are used for preconditioning implants, air-stability, fast procedures, tunable capability and the range of materials that can be coated and used in-vivo is very limited. In BioStealth innovative, robust conditioning of implants with plasma is used for lipid attachment, creating a breakthrough in integration of implants with tissue. A business case will be developed for BioStealth, covering different markets and routes for market introduction. Results of market analysis and financing needs will be combined with science-based technology comparison and used for discussions with potential industry partners. Several companies have already expressed interest in BioStealth.

150 000 €

Start date: 2015-02-01, End date: 2016-07-31

The centromere is one of the most important chromosomal elements. It is required for proper chromosome segregation in mitosis and meiosis and readily recognizable as the primary constriction of mitotic chromosomes. Proper centromere function is essential to ensure genome stability; therefore understanding centromere identity is directly relevant to cancer biology and gene therapy. How centromeres are established and maintained is however still an open question in the field. In most organisms this appears to be regulated by an epigenetic mechanism. The key candidate for such an epigenetic mark is CENH3 (CENP-A in mammals, CID in Drosophila), a centromere-specific histone H3 variant that is essential for centromere function and exclusively found in the nucleosomes of centromeric chromatin. Using a biosynthetic approach of force-targeting CENH3 in Drosophila to non-centromeric DNA, we were able to induce centromere function and demonstrate that CENH3 is sufficient to determine centromere identity. Here we propose to move this experimental setup across evolutionary boundaries into human cells to develop improved human artificial chromosomes (HACs). We will make further use of this unique setup to dissect the function of targeted CENH3 both in Drosophila and human cells. Contributing centromeric components and histone modifications of centromeric chromatin will be characterized in detail by mass spectroscopy in Drosophila. Finally we are proposing to develop a technique that allows high-resolution mapping of proteins on repetitive DNA to help further characterizing known and novel centromere components. This will be achieved by combining two independently established techniques: DNA methylation and DNA fiber combing. This ambitious proposal will significantly advance our understanding of how centromeres are determined and help the development of improved HACs for therapeutic applications in the future.

1 755 960 €

Start date: 2013-02-01, End date: 2019-01-31

Water is the first molecule to come into contact with biomaterials in biological systems and thus essential to the processes of biodegradation, biocompatibility and biofouling. Despite this fact, little is currently known about how biomaterials interact with water. This knowledge is crucial for the development and optimisation of novel functional biomaterials for human health (e.g. biosensing devices, erodible biomaterials, drug release carriers, wound dressings). BioWater will develop near and mid infrared chemical imaging (NIR-MIR-CI) techniques to investigate the fundamental interaction between biomaterials and water in order to understand the key processes of biodegradation, biocompatibility and biofouling. This ambitious yet achievable project will focus on two major categories of biomaterials relevant to human health: extracellular collagens and synthetic biopolymers. Initially, interactions between these biomaterials and water will be investigated; subsequently interactions with more complicated matrices (e.g. protein solutions and cellular systems) will be studied. CI data will be correlated with standard surface characterization, biocompatibility and biodegradation measurements. Molecular dynamic simulations will complement this work to identify the most probable molecular structures of water at different biomaterial interfaces. Advanced understanding of the role of water in biocompatibility, biofouling and biodegradation processes will facilitate the optimization of biomaterials tailored to specific cellular environments with a broad range of therapeutic applications (e.g. drug eluting stents, tissue engineering, wound healing). The new NIR-MIR-CI/chemometric methodologies developed in BioWater will allow for the rapid characterization and monitoring of novel biomaterials at pre-clinical stages, improving process control by overcoming the laborious and time consuming large-scale sampling methods currently required in biomaterials development.

1 487 682 €

Start date: 2014-02-01, End date: 2019-01-31

Breakthroughs in numerical relativity in 2005 gave us unprecedented access to the strong-field regime of general relativity, making possible solutions of the full nonlinear Einstein equations for the merger of two black holes. Numerical relativity is also crucial to study fundamental physics with gravitational-wave (GW) observations: numerical solutions allow us to construct models that will be essential to extract physical information from observations in data from Advanced LIGO and Virgo, which will operate from late 2015. Complete signal models will allow us to follow up our first theoretical predictions of the nature of black-hole mergers with their first observational measurements. The goal of this project is to advance numerical-relativity methods, deepen our understanding of black-hole mergers, and map the parameter space of binary configurations with the most comprehensive and systematic set of numerical calculations performed to date, in order to produce a complete GW signal model. Central to this problem is the purely general-relativistic effect of orbital precession. The inclusion of precession in waveform models is the most challenging and urgent theoretical problem in the build-up to GW astronomy. Simulations must cover a seven-dimensional parameter space of binary configurations, but their computational cost makes a naive covering unfeasible. This project capitalizes on a breakthrough preliminary model produced by my team in 2013, with the pragmatic goal of focussing on the physics that will be measurable with GW detectors over the next five years. My team at Cardiff is uniquely placed to tackle this problem. Since 2005 I have been at the forefront of black-hole simulations and waveform modelling, and the Cardiff group is a world leader in analysis of GW detector data. This project will consolidate my team to make breakthroughs in strong-field gravity, astrophysics, fundamental physics and cosmology using GW observations.

1 998 009 €

Start date: 2015-10-01, End date: 2020-09-30

A fundamental feature of language is that it allows us to reproduce what others have said. It is traditionally assumed that there are two ways of doing this: direct discourse, where you preserve the original speech act verbatim, and indirect discourse, where you paraphrase it in your own words. In accordance with this dichotomy, linguists have posited a number of universal characteristics to distinguish the two modes. At the same time, we are seeing more and more examples that seem to fall somewhere in between. I reject the direct indirect distinction and replace it with a new paradigm of blended discourse. Combining insights from philosophy and linguistics, my framework has only one kind of speech reporting, in which a speaker always attempts to convey the content of the reported words from her own perspective, but can quote certain parts verbatim, thereby effectively switching to the reported perspective. To explain why some languages are shiftier than others, I hypothesize that a greater distance from face-to-face communication, with the possibility of extra- and paralinguistic perspective marking, necessitated the introduction of an artificial direct indirect separation. I test this hypothesis by investigating languages that are closely tied to direct communication: Dutch child language, as recent studies hint at a very late acquisition of the direct indirect distinction; Dutch Sign Language, which has a special role shift marker that bears a striking resemblance to the quotational shift of blended discourse; and Ancient Greek, where philologists have long been observing perspective shifts. In sum, my research combines a new philosophical insight on the nature of reported speech with formal semantic rigor and linguistic data from child language experiments, native signers, and Greek philology.

677 254 €

Start date: 2011-03-01, End date: 2016-08-31

Recent advances in cryptography yielded the blockchain technology, which enables a radically new and decentralized method to maintain authoritative records, without the need of trusted intermediaries. Bitcoin, a cryptocurrency blockchain application has already demonstrated that it is possible to operate a purely cryptography-based, global, distributed, decentralized, anonymous financial network, independent from central and commercial banks, regulators and the state. The same technology is now being applied to other social domains (e.g. public registries of ownership and deeds, voting systems, the internet domain name registry). But research on the societal impact of blockchain innovation is scant, and we cannot properly assess its risks and promises. In addition, crucial knowledge is missing on how blockchain technologies can and should be regulated by law. The BlockchainSociety project focuses on three research questions. (1) What internal factors contribute to the success of a blockchain application? (2) How does society adopt blockchain? (3) How to regulate blockchain? It breaks new ground as it (1) maps the most important blockchain projects, their governance, and assesses their disruptive potential; (2) documents and analyses the social diffusion of the technology, and builds scenarios about the potential impact of blockchain diffusion; and (3) it creates an inventory of emerging policy responses, compares and assesses policy tools in terms of efficiency and impact. The project will (1) build the conceptual and methodological bridges between information law, the study of the self-governance of technological systems via Science and Technology Studies, and the study of collective control efforts of complex socio-technological assemblages via Internet Governance studies; (2) address the most pressing blockchain-specific regulatory challenges via the analysis of emerging policies, and the development of new proposals.

1 499 631 €

Start date: 2018-01-01, End date: 2022-12-31

" Why do people convert to Islam? The contemporary relevance of this question is immediately apparent.""Becoming Muslim"" will transform our knowledge about Islamisation processes and contexts through archaeological research in Harar, Eastern Ethiopia, and examine this in comparison to other regions in sub-Saharan Africa via publication and a major conference. Assessing genuine belief is difficult, but the impact of trade, Saints, Sufis and Holy men, proselytisation, benefits gained from Arabic literacy and administration systems, enhanced power, prestige, warfare, and belonging to the larger Muslim community have all been suggested. Equally significant is the context of conversion. Why were certain sub-Saharan African cities key points for conversion to Islam, e.g. Gao and Timbuktu in the Western Sahel, and Harar in Ethiopia? Archaeological engagement with Islamisation processes and contexts of conversion in Africa is variable, and in parts of the continent research is static. This exciting 4-year project explores, for the first time, Islamic conversion and Islamisation through focusing on Harar, the most important living Islamic centre in the Horn of Africa, and its surrounding region. Islamic archaeology has been neglected in Ethiopia, and is wholly non-existent in Harar. Excavation at 5 key sites: 2 shrines, 2 abandoned settlements, 1 urban site, will permit evaluation of urban Islam, the veneration of saints, pilgrimage and shrine based practices, rural Islam, architecture and jihad, changes in lifeways, and early and comparative evidence for Islam and long-distance trade, through analysis of, e.g. architecture, epigraphy, burial orientation, imported artifacts, and faunal and botanical remains. Although it is fully acknowledged that conversion to Islam and Islamisation processes are not universal, my project is groundbreaking in developing and applying a transferable methodology for the archaeological explanation of ""Becoming Muslim"" in sub-Saharan Africa."

1 031 105 €

Start date: 2016-09-01, End date: 2020-08-31

How does our acting, sensing and feeling body shape our mind? The mechanisms by which bodily signals are integrated and re-represented in the brain, as well as the relation between these processes and body awareness remain unknown. To this date, neuropsychological disorders of body awareness represent an indispensible window of insight into phenomenally rich states of body unawareness. Unfortunately, only few experimental studies have been conducted in these disorders. The BODILY SELF will aim to apply methods from cognitive neuroscience to experimental and neuroimaging studies in healthy volunteers, as well as in patients with neuropsychological disorders of body awareness. A first subproject will assess which combination of deficits in sensorimotor afferent and efferent signals leads to unawareness. The second subproject will attempt to use experimental, psychophysical interventions to treat unawareness and measure the corresponding, dynamic changes in the brain. The third subproject will assess how some bodily signals and their integration is influenced by social mechanisms. The planned studies surpass the existing state-of-the-art in the relevant fields in five ground-breaking ways, ultimately allowing us to (1) acquire an unprecedented ‘on-line’ experimental ‘handle’ over dynamic changes in body awareness; (2) restore awareness and improve health outcomes (3) understand the brain’s potential for reorganisation and plasticity in relation to higher-order processes such as awareness; (4) understand how our own body experience is modulated by our interactions and relations with others; (5) address in a genuinely interdisciplinary manner some of the oldest questions in psychology, philosophy and medicine; how embodiment influences the mind, how others influence the self and how mind–body processes affect healing.

1 453 284 €

Start date: 2013-04-01, End date: 2018-09-30

This program’s goal is to develop a scaffold using a new biomaterial source that is functionalised with on-demand delivery of genes for coordinated healing of diabetic foot ulcers (DFUs). DFUs are chronic wounds that are often recalcitrant to treatment, which devastatingly results in lower leg amputation. This project builds on the PI’s experience growing matrix from induced-pluripotent stem cell derived (iPS)-fibroblasts and in developing on-demand drug delivery technologies. The aim of this project is to first develop a SiPS: a scaffold from iPS-fibroblast grown matrix, which has never been tested as a source material for scaffolds. iPS-fibroblasts grow a more pro-repair and angiogenic matrix than (non-iPS) adult fibroblasts. The SiPS structure will be bilayered to mimic native skin: dermis made mostly by fibroblasts and epidermis made by keratinocytes. The dermal layer will consist of a porous scaffold with optimised pore size and mechanical properties and the epidermal layer will be film-like, optimised for keratinisation. Second, the SiPS will be functionalised with delivery of plasmid-DNA (platelet derived growth factor gene, pPDGF) to direct angiogenesis on-demand. As DFUs undergo uncoordinated healing, timed pPDGF delivery will guide them through angiogenesis and healing. To achieve this, alginate microparticles, designed to respond to ultrasound by releasing pPDGF, will be interspersed throughout the SiPS. This BONDS will be tested in an in vivo pre-clinical DFU model to confirm its ability to heal wounds by providing cells with the appropriate biomimetic scaffold environment and timed directions for healing. With >100 million current diabetics expected to get a DFU, the BONDS would have a powerful clinical impact. This research program combines a disruptive technology, the SiPS, with a new platform for on-demand delivery of pDNA to heal DFUs. The PI will build his lab around these innovative platforms, adapting them for treatment of diverse complex wounds.

1 372 135 €

Start date: 2017-10-01, End date: 2022-09-30