ERC FUNDED PROJECTS

This research will create a new theoretical vision of the importance of marriage as an agent of transformation in human sociality. Marriage globally is undergoing profound change, provoking intense debate and anxiety. These concerns refract wider instabilities in political, economic, and familial institutions. They signal the critical role of marriage in bringing together - and separating - intimate, personal, and familial life with wider state institutions. But we have little up to date comparative research or general theory of how marriage changes or the long-term significance of such change. Paradoxically, social scientific and public discourse emphasise the conservative and normative aspects of marriage. This underlines the need for a new theoretical frame that takes account of cultural and historical specificity to grasp the importance of marriage as both vehicle of and engine for transformation. AGATM overturns conventional understandings by viewing marriage as inherently transformative, indeed at the heart of social and cultural change. The research will investigate current transformations of marriage in two distinct senses. First, it will undertake an ethnographic investigation of new forms of marriage in selected sites in Europe, N. America, Asia, and Africa. Second, it will subject ‘marriage’ to a rigorous theoretical critique that will denaturalise marriage and reintegrate it into the new anthropology of kinship. Research on five complementary and contrastive sub-projects examining emerging forms of marriage in different locations will be structured through the themes of care, property, and ritual forms. The overarching analytic of temporality will frame the theoretical vision of the research and connect the themes. The resulting six monographs, journal articles, and exhibition will together revitalise the study of kinship by placing the moral, practical, political, and imaginative significance of marriage over time at its centre.

2 297 584 €

Start date: 2017-01-01, End date: 2021-12-31

By the end of the 4th year of the ERC Advanced grant, the PI has set up the basis of a unique procedure to perform optical coherence tomography (OCT) that is similar in outcome to time domain interferometry but has all advantages of spectral domain interferometry in terms of speed and sensitivity. The new method of OCT, termed as Master/Slave (MS), is characterised by several advantages: direct production of an en-face OCT image, tolerance to dispersion that allows MS-OCT to achieve the theoretical limit of axial resolution and sensitivity that can be tailored for no hardware and time cost, with the axial resolution. By excellence, the Master/Slave OCT method delivers en-face views direct, allowing lower cost hardware and faster provision of en-face slicing and visualisation. An essential advantage is that of parallel processing, that makes MS-OCT, ideally suited to novel parallel optical configurations and graphic processing units (GPU). These advantages can substantially increase the speed in providing volumes of the tissue, making the new OCT method superior to all other methods on the market. The POC support will help advance the MS-OCT closer to commercialisation. Four market strategies are identified with immediate products for the first two. OCT add-on modules, equipped with MS software, for: A. OCT developers, to accelerate their research and B. OCT developers that can modify existing commercial OCT systems, by making them accomplish the MS protocol. The module to be assembled and assessed for commercialisation will also pave the way to two more strategies: C. Companies already selling OCT systems on dedicated markets, where specialised agreements will widen the market and even D. A full OCT system created by the new company, an ultimate outcome that requires investment, based on revenue acquired by selling the add-on modules.

149 917 €

Start date: 2015-11-01, End date: 2017-04-30

This proposal outlines a plan to combine Charge Couple Device (CCD) camera technologies with two-phase Liquid Argon Time Projection Chambers (LAr TPCs) utilising THick Gas Electron Multipliers (THGEMs) to evolve a next generation neutrino detector. This will be an entirely new readout option, and will open the prospect of revolutionary discoveries in fundamental particle physics. Furthermore, the Compton imaging power of this technology will be developed, which will have diverse applications in novel medical imaging techniques and detection of concealed nuclear materials. Colossal LAr TPCs are the future for long-baseline-neutrino-oscillation physics around which the international neutrino community is rallying, with the common goal of discovering new physics beyond the Standard Model, which holds the key to our understanding of phenomena such as dark matter and the matter-antimatter asymmetry. I have successfully provided a first demonstration of photographic capturing of muon tracks and single gammas interacting in the Liverpool 40 l LAr TPC using a CCD camera and THGEM. I propose an ambitious project of extensive research to mature this innovative LAr optical readout technology. I will construct a 650 l LAr TPC with integrated CCD/THGEM readout, capable of containing sufficient tracking information for full development and characterisation of this novel detector, with the goal of realising this game-changing technology in the planned future giant LAr TPCs. Camera readout can replace the current charge readout technology and associated scalability complications, and the excellent energy thresholds will enhance detector performance as well as extend research avenues to lower energy fundamental physics. Also, I will explore the Compton imaging capability of LAr CCD/THGEM technology; the superiority of the energy threshold and spatial resolution of this system can offer significant advancement to medical imaging and the detection of concealed nuclear materials.

1 837 911 €

Start date: 2016-03-01, End date: 2021-02-28

‘Consistency’ is regularly cited as a desirable attribute of border control, but it has received little critical social scientific attention. This inter-disciplinary project, at the inter-face between critical human geography, border studies and law, will scrutinise the consistency of European asylum adjudication in order to develop richer theoretical understanding of this lynchpin concept. It will move beyond the administrative legal concepts of substantive and procedural consistency by advancing a three-fold conceptualisation of consistency – as everyday practice, discursive deployment of facts and disciplinary technique. In order to generate productive intellectual tension it will also employ an explicitly antagonistic conceptualisation of the relationship between geography and law that views law as seeking to constrain and systematise lived space. The project will employ an innovative combination of methodologies that will produce unique and rich data sets including quantitative analysis, multi-sited legal ethnography, discourse analysis and interviews, and the findings are likely to be of interest both to academic communities like geographers, legal and border scholars and to policy makers and activists working in border control settings. In 2013 the Common European Asylum System (CEAS) was launched to standardise the procedures of asylum determination. But as yet no sustained multi-methodological assessment of the claims of consistency inherent to the CEAS has been carried out. This project offers not only the opportunity to assess progress towards harmonisation of asylum determination processes in Europe, but will also provide a new conceptual framework with which to approach the dilemmas and risks of inconsistency in an area of law fraught with political controversy and uncertainty around the world. Most fundamentally, the project promises to debunk the myths surrounding the possibility of fair and consistent border controls in Europe and elsewhere.

1 252 067 €

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

This project focuses on Sun-like stars, which possess convective envelopes and universally exhibit magnetic activity (in the mass range 0.1 to 1.3 MSun). The rotation of these stars influences their internal structure, energy and chemical transport, and magnetic field generation, as well as their external magnetic activity and environmental interactions. Due to the huge range of timescales, spatial scales, and physics involved, understanding how each of these processes relate to each other and to the long-term evolution remains an enormous challenge in astrophysics. To face this challenge, the AWESoMeStars project will develop a comprehensive, physical picture of the evolution of stellar rotation, magnetic activity, mass loss, and accretion. In doing so, we will (1) Discover how stars lose the vast majority of their angular momentum, which happens in the accretion phase (2) Explain the observed rotation-activity relationship and saturation in terms of the evolution of magnetic properties & coronal physics (3) Characterize coronal heating and mass loss across the full range of mass & age (4) Explain the Skumanich (1972) relationship and distributions of spin rates observed in young clusters & old field stars (5) Develop physics-based gyrochronology as a tool for using rotation rates to constrain stellar ages. We will accomplish these goals using a fundamentally new and multi-faceted approach, which combines the power of multi-dimensional MHD simulations with long-timescale rotational-evolution models. Specifically, we will develop a next generation of MHD simulations of both star-disk interactions and stellar winds, to model stars over the full range of mass & age, and to characterize how magnetically active stars impact their environments. Simultaneously, we will create a new class of rotational-evolution models that include external torques derived from our simulations, compute the evolution of spin rates of entire star clusters, & compare with observations.

2 206 205 €

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

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

Speciation is a central process in evolution that involves the origin of barriers to gene flow between populations. Species are typically isolated by several barriers and assembly of multiple barriers separating the same populations seems to be critical to the evolution of strong reproductive isolation. Barriers resulting from direct selection can become coincident through a process of coupling while reinforcement can add barrier traits that are not under direct selection. In the presence of gene flow, these processes are opposed by recombination. While recent research using the latest sequencing technologies has provided much increased knowledge of patterns of differentiation and the genetic basis of local adaptation, it has so far added little to understanding of the coupling and reinforcement processes. In this project, I will focus on the accumulation of barriers to gene exchange and the processes underlying increasing reproductive isolation. I will use the power of natural contact zones, combined with novel manipulative experiments, to separate the processes that underlie patterns of differentiation and introgression. The Littorina saxatilis model system allows me to do this with both local replication and a contrast between distinct spatial contexts on a larger geographic scale. I will use modelling to determine how processes interact and to investigate the conditions most likely to promote coupling and reinforcement. Overall, the project will provide major new insights into the speciation process, particularly revealing the requirements for progress towards complete reproductive isolation.

2 499 927 €

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

Cooling is essential for food and drinks, medicine, electronics and thermal comfort. Thermal changes due to pressure-driven phase transitions in fluids have long been used in vapour compression systems to achieve continuous refrigeration and air conditioning, but their energy efficiency is relatively low, and the working fluids that are employed harm the environment when released to the atmosphere. More recently, the discovery of large thermal changes due to pressure-driven phase transitions in magnetic solids has led to suggestions for environmentally friendly solid-state cooling applications. However, for this new cooling technology to succeed, it is still necessary to find suitable barocaloric (BC) materials that satisfy the demanding requirements set by applications, namely very large thermal changes in inexpensive materials that occur near room temperature in response to small applied pressures. I aim to develop new BC materials by exploiting phase transitions in non-magnetic solids whose structural and thermal properties are strongly coupled, namely ferroelectric salts, molecular crystals and hybrid materials. These materials are normally made from cheap abundant elements, and display very large latent heats and volume changes at structural phase transitions, which make them ideal candidates to exhibit extremely large BC effects that outperform those observed in state-of-the-art BC magnetic materials, and that match applications. My unique approach combines: i) materials science to identify materials with outstanding BC performance, ii) advanced experimental techniques to explore and exploit these novel materials, iii) materials engineering to create new composite materials with enhanced BC properties, and iv) fabrication of BC devices, using insight gained from modelling of materials and device parameters. If successful, my ambitious strategy will culminate in revolutionary solid-state cooling devices that are environmentally friendly and energy efficient.

1 467 521 €

Start date: 2016-04-01, End date: 2021-03-31

The agile and efficient flight of birds shows what flight performance is physically possible, and in theory could be achieved by unmanned air vehicles (UAVs) of the same size. The overall aim of this project is to enhance the performance of small scale UAVs by developing novel technologies inspired by understanding how birds are adapted to interact with airflows. Small UAVs have the potential to dramatically change current practices in many areas such as, search and rescue, surveillance, and environmental monitoring. Currently the utility of these systems is limited by their operational endurance and their inability to operate in strong turbulent winds, especially those that often occur in urban environments. Birds are adapted to be able to fly in these conditions and actually use them to their advantage to minimise their energy output. This project is composed of three tracks which contain elements of technology development, as well as scientific investigation looking at bird flight behaviour and aerodynamics. The first track looks at developing path planning algorithms for UAVs in urban environments based on how birds fly in these areas, by using GPS tracking and computational fluid dynamics alongside trajectory optimization. The second track aims to develop artificial wings with improved gust tolerance inspired by the features of feathered wings. Here, high speed video measurements of birds flying through gusts will be used alongside wind tunnel testing of artificial wings to discover what features of a bird’s wing help to alleviate gusts. The third track develops novel force and flow sensor arrays for autonomous flight control based on the sensor arrays found in flying animals. These arrays will be used to make UAVs with increased agility and robustness. This unique bird inspired approach uses biology to show what is possible, and engineering to find the features that enable this performance and develop them into functional technologies.

1 998 546 €

Start date: 2016-04-01, End date: 2021-03-31

Contemporary organizations face three interrelated, but analytically distinguishable, challenges. First, they should be alert to mistakes that could be catastrophic. Second, they need to allocate attention, especially to correct past mistakes and to make accurate predictions about future developments. Third, they should be innovative, able to stand out from existing categories while being recognized as outstanding. This project investigates these cognitive challenges with the aim of developing a comprehensive sociological approach to study the social properties of cognition. Research on error detection, attention allocation, and recognizant innovation will be conducted in three distinct settings strategically chosen so the scale and complexity of the performance challenges increases across the cases. The research question that cuts across the socio-cognitive challenges asks whether and how diversity contributes to performance. 1) We first test whether social context, understood at the most basic level as the composition of a small collectivity, affects the cognitive activity of pricing. To do so, I use experimental market methods to test whether ethnic and gender diversity deflate price bubbles by disrupting herding behaviour. 2) The second study tests how the social structure of attention affects valuation. The activities involve error correction and accuracy of prediction in estimates by securities analysts; the method is two-mode network analysis; and the timing, intensity, and diversity of attention networks are the effects to be tested. 3) Whereas my first two tests examine relations among competitors, my third examines relations within and across collaborative teams. In studying the network properties of creativity, the challenge is recognizant innovation, the activity involves recording sessions in the field of music, the method is cultural network analysis, and the effects to be tested are the combined effects of stylistic diversity and social structure.

2 492 033 €

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

Malaria remains a major problem of public health in developing countries. It is responsible for about 600000 deaths per year, predominantly children in sub-Saharan Africa. There is an urgent need for novel therapies as resistance against current treatments is widespread. The complex parasite biology requires a multifaceted approach targeting multiple life cycle stages and virulence pathways. The pathogenesis of the most deadly of human malaria parasites, Plasmodium falciparum, is related to the capability of infected red blood cells to sequester in deep tissues. Sequestration is critical for the completion of the red blood cell cycle because the release of parasites into the blood circulation allows recognition by surveillance macrophages and clearance in the spleen. A series of studies have since led to the understanding that sequestration of asexually replicating parasites is caused by the adherence of parasite infected red blood cells to the vascular endothelium of various tissues in the body. We have recently demonstrated that gametocytes, the only stage capable of transmission to the mosquito vector, develop in the extravascular environment of the human bone marrow. Preliminary studies in the mouse model have confirmed this finding and also suggest existence of an asexual reservoir in the bone marrow. In this innovative multidiscipinary proposal we aim to investigate the host pathogen interactions at the interface between infected red blood cell and bone marrow vasculature. Specifically we will focus on the following questions: how do parasites home to bone marrow? What are the changes in the bone marrow endothelium upon infection? How do parasites adhere with and transmigrate across the vascular endothelium in the bone marrow? The proposed studies initiate detailed characterization of a new paradigm in malaria parasite interaction with the host vasculature and provide a compelling new avenue for intervention strategies.

2 298 557 €

Start date: 2016-06-01, End date: 2021-05-31

Non-invasive Brain Machine Interfaces (BMI) bring great promise for neuro-rehabilitation and neuro-prosthesis, as well as for brain control of everyday devices and performance of simple tasks. Over the last 15 years the interest in BMIs has grown substantially, and a variety of interfaces have been developed. The field has been growing dramatically, and market studies reveal an estimated market size of $1.46 billion by 2020. However, non-invasive BMIs have failed to reach the impressive control seen by BMIs implanted in the brain. To date, they require considerable training to reach a moderate level of control, they are susceptible to noise and interference, do not generalize between people and devices, and performance does not show long-term consolidation. Results from our ERC-funded work uncovered a new paradigm that dramatically improves these issues. We propose to develop a prototype for a novel, standalone, non-invasive, noise-resistant BMI, based on an unexplored BMI learning paradigm. In this POC we will 1) refine the brain signal interface (decoder) to be automatically customizable to each individual and produces faster training, 2) implement our BMI technology into a portable hardware-based system, and 3) develop a virtual reality/gaming training platform that will increase learning, performance and consolidation of BMI control. In addition to these technical aims, we propose to explore commercial opportunities and societal benefits, in particular in the health sector. We will conduct market analysis and develop a business case for this product, while expanding industry contacts for production and commercialization. The work proposed in this PoC grant will permit, for the first time to our knowledge, the development of a portable, stand-alone, noise-resistant, and easy to learn BMI, applicable across a wide set of devices, which will bring a significant social impact in health, entertainment and other applications.

149 625 €

Start date: 2016-09-01, End date: 2018-02-28

The last few years have seen an explosion in our knowledge of extra-solar planetary systems. However, most exoplanetary systems look nothing like our own: we see “hot Jupiters” which take just days to orbit their parent stars, planets which meander across entire solar systems on highly eccentric orbits, and even planets orbiting twin, binary suns. These planets formed in relatively homogenous discs of cold dust and gas around young, newly-formed stars, but we do not yet understand how this extraordinarily diverse range of planetary architectures was assembled. BuildingPlanS will establish how the observed architectures of exoplanets link to the physics of their formation. My team will build comprehensive models of the assembly of planetary systems, in order to: 1) understand how systems of giant planets are built. 2) understand the assembly of compact, tightly-packed planetary systems. 3) determine where and when planets form around binary stars. By focusing on the three main types of known planetary systems we will determine how key physical processes operate in a wide variety of different environments, and build up a detailed understanding of how planetary systems form and evolve. Recently I have played a key role in developing a robust theory of how young, gas-rich protoplanetary discs evolve; this project will establish how these new ideas shape the formation and evolution of planetary systems. My team will consider how forming and newly-formed planets interact with their parent discs, in order to understand the architectures of young planetary systems. We will then follow how these young systems evolve to maturity over billions of years, and test our results against both new observations of planet-forming discs and our ever-growing census of exoplanetary systems. The overall aim of BuildingPlanS is to link exoplanet architectures with their formation and establish a global picture of how planetary systems are built.

1 945 721 €

Start date: 2016-06-01, End date: 2021-05-31

Recent advances in magnetic resonance (MR) acquisition technology are providing us with images of the human brain of increasing detail and resolution. While these images hold promise to greatly increase our understanding of such a complex organ, the neuroimaging community relies on tools (e.g. SPM, FSL, FreeSurfer) which, being over a decade old, were designed to work at much lower resolutions. These tools do not consider brain substructures that are visible in present-day scans, and this inability to capitalize on the vast improvement of MR is hampering progress in the neuroimaging field. In this ambitious project, which lies at the nexus of medical histology, neuroscience, biomedical imaging, computer vision and statistics, we propose to build a set of next-generation computational tools that will enable neuroimaging studies to take full advantage of the increased resolution of modern MR technology. The core of the tools will be an ultra-high resolution probabilistic atlas of the human brain, built upon multimodal data combining from histology and ex vivo MR. The resulting atlas will be used to analyze in vivo brain MR scans, which will require the development of Bayesian segmentation methods beyond the state of the art. The developed tools, which will be made freely available to the scientific community, will enable the analysis of MR data at a superior level of structural detail, opening completely new opportunities of research in neuroscience. Therefore, we expect the tools to have a tremendous impact on the quest to understand the human brain (in health and in disease), and ultimately on public health and the economy.

1 450 075 €

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

Music and language share similar properties and are processed in overlapping brain regions. As a common information-bearing element in music and language, pitch plays an essential role in encoding musical melodies, signifying linguistic functions, and conveying emotions through music and speech. However, two distinct neurodevelopmental disorders, congenital amusia (CA) and autism spectrum disorders (ASD), affecting millions of people in Europe and worldwide, may selectively impair individuals’ ability to process musical, linguistic, and emotional pitch. To date, it remains unclear why individuals with CA and ASD exhibit significant differences in music, speech, and emotion processing. Under our Delicate Form-Function Balance Hypothesis, we will conduct a series of behavioural and neurophysiological experiments to test the central hypothesis that normal musical, linguistic, and emotional functioning requires a delicate balance in the encoding and decoding of form and function in musical, speech, and emotional communication, with musical communication centred on form and linguistic and emotional communication focused on function. Most critically, we hypothesize that the differences in music, speech, and emotional processing in CA and ASD are rooted not only in pitch and cognitive abilities, but also in the balance between form and function for each domain. Addressing three specific aims regarding the impacts of cognitive processing styles, pitch processing skills, and language background (tone vs. non-tonal) on the behavioural and neurophysiological characteristics of music, language, and emotion processing in CA and ASD, this research will not only help reveal the underlying mechanisms of the two defining aspects of human cognition, music and language, but also form a laboratory for testing key hypotheses about the bio-behavioural manifestations of human neurodevelopmental disorders in music and language processing.

1 488 814 €

Start date: 2016-12-01, End date: 2021-11-30

At least 10% of mothers and 5% of fathers have a mental illness. Family, educational and social lives of children and adolescents with parental mental illness (CAPRI) are disrupted by deprivation and repeated hospitalisation. This is an urgent political and public health concern. The Child and Adolescent Mental Health in Europe (CAMHEE) report urges us ‘to acknowledge and attend to the needs of children and families with parental mental health... ’ recommending better information on CAPRI risks and resilience so interventions can target those at highest risk. This groundbreaking interdisciplinary programme exploits my unique combination of expertise in epidemiology and neuroscience to deliver on CAMHEE objectives for CAPRI. Previous work focuses on these ‘high risk’ children primarily to examine mental illness heritability. In a crucial departure from this, Work Packages (WP) 1 and 2 exploit my collaborations in Sweden and Australia to create unique linkage across 3 population datasets. This will detail CAPRI numbers and a broad range of life outcomes disentangling effects of social adversity over time. But population epidemiology alone cannot reveal how risk creates effects in individuals. To understand ‘how’ to identify ‘who’ we target for costly interventions, WP 3 links the epidemiology with powerful neuroimaging (near infrared spectroscopy NIRS) to discover which at-risk infants of mothers with severe mental illness show abnormal cognitive development at the level of individual brain. This work capitalises on my role at the University of Manchester, one of the leading academic psychiatry and imaging centres in the UK, to create a new Centre in Bioepidemiology. My future aim is that epidemiological profiling combined with NIRS biomarkers of cognition in individuals will identify which high risk children need what intervention. Future work can then evaluate different interventions and fits seamlessly with my research goal to improve the life outcomes of CAPRI.

1 999 338 €

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

Eusociality, in which workers sacrifice their own reproduction to rear the offspring of queens, is a major focus of interest in evolutionary biology. A key aim during recent decades has been to understand the conflicts of interest within eusocial groups. In contrast, however, little is known about the underlying genetic architecture. In this proposal, we will use a mixture of field experiments and transcriptomics to address novel questions about the evolutionary dynamics of queen-worker interactions. Borrowing concepts from the field of sexual conflict, we will investigate a new idea: that the productivity of social groups is limited because castes are constrained by inter-caste genetic correlations from simultaneously reaching their optimal (dimorphic) phenotypes. We will also quantify caste dimorphism across an environmental gradient, and investigate the plasticity of dimorphism using transplants and social manipulations. In addition, we will cross-foster individuals between nests to test for coadaptation between queens and workers. And we will test a long-standing hypothesis experimentally for the first time: that queens manipulate worker phenotype in their own interests. The proposed research will force us to look at eusociality in a completely new way. How caste dimorphism can evolve, the possibility that its evolution could be limited by genetic constraints, and the processes that could resolve those constraints, are topics that have hardly been considered. Recent research has strongly emphasized conflict between queens and workers, but the coadaptation of complementary phenotypes may be just as important. Our approach will be multidisciplinary: we will capitalize on state-of-the-art transcriptomic technology in combination with innovative field methods, and use study systems that allow exceptional sample sizes to be obtained in the wild, where natural selection operates. The overall result will be a new and exciting perspective on queen-worker coevolution.

2 424 263 €

Start date: 2017-01-01, End date: 2021-12-31

Centrioles assemble centrosomes and cilia/flagella, critical structures for cell division, polarity, motility and signalling, which are often deregulated in human disease. Centriole inheritance, in particular the preservation of their copy number and position in the cell is critical in many eukaryotes. I propose to investigate, in an integrative and quantitative way, how centrioles are formed in the right numbers at the right time and place, and how they are maintained to ensure their function and inheritance. We first ask how centrioles guide their own assembly position and centriole copy number. Our recent work highlighted several properties of the system, including positive and negative feedbacks and spatial cues. We explore critical hypotheses through a combination of biochemistry, quantitative live cell microscopy and computational modelling. We then ask how the centrosome and the cell cycle are both coordinated. We recently identified the triggering event in centriole biogenesis and how its regulation is akin to cell cycle control of DNA replication and centromere assembly. We will explore new hypotheses to understand how assembly time is coupled to the cell cycle. Lastly, we ask how centriole maintenance is regulated. By studying centriole disappearance in the female germline we uncovered that centrioles need to be actively maintained by their surrounding matrix. We propose to investigate how that matrix provides stability to the centrioles, whether this is differently regulated in different cell types and the possible consequences of its misregulation for the organism (infertility and ciliopathy-like symptoms). We will take advantage of several experimental systems (in silico, ex-vivo, flies and human cells), tailoring the assay to the question and allowing for comparisons across experimental systems to provide a deeper understanding of the process and its regulation.

2 000 000 €

Start date: 2017-01-01, End date: 2021-12-31

Our aim is to dissect the mechanisms of contact inhibition of locomotion (CIL), a process whereby migrating cells collide and repel each other, as it is now clear that CIL is pivotal to understanding embryogenesis and pathologies such as cancer. We have developed an in vivo model using Drosophila macrophages (hemocytes), along with novel analytical tools, to examine the contact inhibition response in cells during development. We therefore have an unprecedented opportunity to address CIL in a genetically tractable organism within a physiologically relevant setting. This model has revealed that a precisely controlled CIL response is a significant driving force behind the acquisition of embryonic patterns, and recent data show that this precision requires a series of synchronized changes in cytoskeletal dynamics. Our central hypothesis is that key to this cellular ‘dance’ is mechanosensation of the collision, which integrates subsequent signaling mechanisms to choreograph the steps of the contact inhibition process. The first part of this proposal will elucidate the molecular mechanisms controlling CIL by exploiting our unique ability to live image and genetically dissect this process in Drosophila. We will also take an interdisciplinary approach to elucidate the mechanical aspects of the response, which will allow us to examine the feedback between signaling pathways and the physical forces of the CIL response. We will subsequently extend our detailed understanding of the CIL process, and our novel set of analytical tools, to mammalian cell types and model systems. This will allow us to develop new assays to directly probe the mechanics of CIL and begin to investigate the function of this underexplored process in other cell types. This in depth knowledge of the response places us in the best position to extend our understanding of CIL to new physiologically relevant scenarios that in the future will impact on human health.

1 993 803 €

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

As elsewhere in Europe, Anglo-Saxon England saw a development from an oral, vernacular, native, and pagan culture to one that was primarily literate, Latinate, imported, and Christian; and such a transition is clearest in Anglo-Saxon verse. CLASP will focus on all surviving verse of Anglo-Saxon England, composed in Old English and Anglo-Latin over a period of over four centuries (c. 670–1100 CE), and produce for the first time an online and interactive consolidated library, marked up through TEI P5 XML to facilitate the identification of idiosyncratic features of sound, metre, spellings, diction, syntax, formulas, themes, and genres across the entire corpus, so forging connections and suggesting more certain chains of influence both within and between the two main literary languages of Anglo-Saxon England. The bilingual corpus comprises almost 60,000 lines of poetry, with about half surviving in each language, and mostly appearing in only a single witness, usually in manuscript. More than fifty named poets are identified, many of them dateable with more or less precision, whose influence on each other can be closely documented, while in the case of anonymous verse, most of which is in Old English, the focus will be on tracing potential influence between texts, to establish a comparative rather than an absolute chronology. CLASP will use the full panoply of digital resources, including sound- and image-files where relevant, to make the oldest surviving poetry in England available to a modern audience for unprecedented kinds of exploration, comprehensive analysis, and interrogation, and in a series of conferences, workshops, and other publications will show the potential of such a comprehensive multilingual corpus to revolutionize perspectives not only on Anglo-Saxon England, but elsewhere in Europe, where Latin and the vernacular likewise co-existed in a Christian context across centuries.

2 443 640 €

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

CLONAL AND CELLULAR HETEROGENEITY OF BREAST CANCER AND ITS DYNAMIC EVOLUTION WITH TREATMENT Breast cancer remains one of the leading causes of cancer death in women. One of the greatest challenges is that breast cancer is a heterogeneous group of 10 diseases defined by genomic profiling. In addition, each tumor is composed of clones and clonal evolution underpins the successive acquisition of the hallmarks of cancer, including metastasis and resistance to therapy. Furthermore tumors display biologically and clinically relevant cellular heterogeneity: immune system, vasculature, and stroma. This cellular heterogeneity both shapes and is shaped by the malignant compartment and modulates response to therapy. This proposal will use longitudinal studies to unravel the clonal and cellular heterogeneity of breast cancer and its dynamic evolution with treatment. The overall goal is to provide a systems level view of evolving clonal and cellular architectures in space and time along the clinical continuum of breast cancers in the clinic, leading to the discovery of new biological and clinical paradigms which will transform our understanding of the disease. The overall approach is to capture the evolution of clonal and cellular heterogeneity of breast cancers in space and time using unique clinical cohorts where samples (biopsies and blood/plasma) are available spanning the whole disease continuum: early breast cancer surgically treated with curative intent, neo-adjuvant therapy, and matched relapse/metastasis. The 4 aims of the proposal are: 1. Characterization of the clonal and cellular heterogeneity of primary tumours from the 10 genomic driver-based breast cancer subtypes (ICs) 2. Comparative characterization of the clonal and cellular heterogeneity of matched pairs of primary and metastatic cancers 3. Characterization of the clonal and epigenetic evolution across therapy courses 4. Characterization of the immune response across therapy courses

2 497 660 €

Start date: 2017-01-01, End date: 2021-12-31

During the human lifetime 10000 trillion cell divisions take place to ensure tissue homeostasis and several vital functions in the organism. Mitosis is the process that ensures that dividing cells preserve the chromosome number of their progenitors, while deviation from this, a condition known as aneuploidy, represents the most common feature in human cancers. Here we will test two original concepts with strong implications for chromosome segregation fidelity. The first concept is based on the “tubulin code” hypothesis, which predicts that molecular motors “read” tubulin post-translational modifications on spindle microtubules. Our proof-of-concept experiments demonstrate that tubulin detyrosination works as a navigation system that guides chromosomes towards the cell equator. Thus, in addition to regulating the motors required for chromosome motion, the cell might regulate the tracks in which they move on. We will combine proteomic, super-resolution and live-cell microscopy, with in vitro reconstitutions, to perform a comprehensive survey of the tubulin code and the respective implications for motors involved in chromosome motion, mitotic spindle assembly and correction of kinetochore-microtubule attachments. The second concept is centered on the recently uncovered chromosome separation checkpoint mediated by a midzone-associated Aurora B gradient, which delays nuclear envelope reformation in response to incompletely separated chromosomes. We aim to identify Aurora B targets involved in the spatiotemporal regulation of the anaphase-telophase transition. We will establish powerful live-cell microscopy assays and a novel mammalian model system to dissect how this checkpoint allows the detection and correction of lagging/long chromosomes and DNA bridges that would otherwise contribute to genomic instability. Overall, this work will establish a paradigm shift in our understanding of how spatial information is conveyed to faithfully segregate chromosomes during mitosis.

2 323 468 €

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

Colour vision deficiency (CVD) is a genetic disorder of colour vision that affects 7.4% of European males and 0.4% of European females. Although there are reliable tests for diagnosing CVD in adults and older children, there are only a few tests for young children, and fundamental issues with these tests render them unreliable. For example, colours used in the tests are too similar for young children to discriminate given their immature colour vision, tasks are too difficult for them to complete, tests either over- or under-diagnose CVD, or are not widely accessible. Therefore, the current situation is that CVD can be reliably diagnosed only from about 5 years onwards. Earlier diagnosis would enable steps to be taken to ensure CVD children are not disadvantaged in early years education that relies on colour coded schemes and materials. Our goal is to develop, evaluate and bring to market an age-appropriate early years test for CVD. Our research on the ERC funded ‘CATEGORIES’ project is investigating the development of colour perception in over 1400 infants and toddlers. This extensive testing has given us specialist insight into the exact colours that are appropriate for an early years test for CVD. We have also developed age-appropriate tasks that measure young children’s responses to colour in a reliable and efficient manner. In the current project we propose to develop an early years CVD test in the form of an app. The test will use the colours that we have defined and the tasks that we have developed, and we aim for it to provide an accurate CVD diagnosis. The project will take the test to proof of concept and will establish the scientific validity, technical feasibility and commercialisation process. We aim that the test will be the ‘gold standard’ for educators, clinicians, scientists and parents. This will ensure that CVD can be detected earlier than is currently the case, bringing important and tangible benefits for education, clinical practice and research.

149 645 €

Start date: 2016-12-01, End date: 2018-05-31

The modern financial system has undergone immense transformation in recent years and is far more complex than ever before. In lockstep, financial regulation has also become more complex. This research proposal attempts to improve our understanding of potential drivers of this complexity and the implications of this change on the allocation of resources. Taking a positive rather than a normative approach, I will analyse post-crisis changes at both the micro- and at the macro-levels to create a broader understanding of complexities in the current financial system. In order to do so, I will employ a set of advanced research designs, as well as a uniquely assembled micro-level dataset covering state and privately owned financial institutions in Asia, Africa, South America and Europe. This project will focus on two interconnected areas of research: 1) Organisation of Credit, 2) Financial regulation in a complex environment. The aim of this project is to create a sustainable framework for the study of post-crisis financial systems, and to shape the current debate on the future of post-crisis financial structures and the development of policy in this area. Not only will this research have a considerable impact on our understanding of financial systems, it will also impact fields beyond finance, like Organisational Economics, Industrial Organisation and Development Economics.

1 498 947 €

Start date: 2016-04-01, End date: 2021-03-31