ERC FUNDED PROJECTS

Parkinson’s disease (PD) is the second most common neurodegenerative disorder primarily caused by the progressive loss of dopaminergic (DA) neurons in the substantia nigra (SN). Despite the advances in gene discovery associated with PD, the knowledge of the PD pathogenesis is largely limited to the involvement of these genes in the generic cell death pathways, and why degeneration is specific to DA neurons and why the degeneration is progressive remain enigmatic. Broad goal of our work is therefore to elucidate the mechanisms underlying specific and progressive DA neuron degeneration in PD. Our new Drosophila model of PD ⎯Fer2 gene loss-of-function mutation⎯ is unusually well suited to address these questions. Fer2 mutants exhibit specific and progressive death of brain DA neurons as well as severe locomotor defects and short life span. Strikingly, the death of DA neuron is initiated in a small cluster of Fer2-expressing DA neurons and subsequently propagates to Fer2-negative DA neurons. We therefore propose a novel two-step model of the neurodegeneration in PD: primary cell death occurs in a specific subset of dopamindegic neurons that are genetically defined, and subsequently the failure of the neuronal connectivity triggers and propagates secondary cell death to remaining DA neurons. In this research, we will test this hypothesis and investigate the underlying molecular mechanisms. This will be the first study to examine circuit-dependency in DA neuron degeneration. Our approach will use a combination of non-biased genomic techniques and candidate-based screening, in addition to the powerful Drosophila genetic toolbox. Furthermore, to test this hypothesis beyond the Drosophila model, we will establish new mouse models of PD that exhibit progressive DA neuron degeneration. Outcome of this research will likely revolutionize the understanding of PD pathogenesis and open an avenue toward the discovery of effective therapy strategies against PD.

1 518 960 €

Start date: 2013-06-01, End date: 2018-05-31

At the end of their life, stars spread their inner material into the diffuse interstellar medium. This diffuse medium gets locally denser and form dark clouds (also called dense or molecular clouds) whose innermost part is shielded from the external UV field by the dust, allowing for molecules to grow and get more complex. Gravitational collapse occurs inside these dense clouds, forming protostars and their surrounding disks, and eventually planetary systems like (or unlike) our solar system. The formation and evolution of molecules, minerals, ices and organics from the diffuse medium to planetary bodies, their alteration or preservation throughout this cosmic chemical history set the initial conditions for building planets, atmospheres and possibly the first bricks of life. The current view of interstellar chemistry is based on fragmental works on key steps of the sequence that are observed. The objective of this proposal is to follow the fractionation of the elements between the gas-phase and the interstellar grains, from the most diffuse medium to protoplanetary disks, in order to constrain the chemical composition of the material in which planets are formed. The potential outcome of this project is to get a consistent and more accurate description of the chemical evolution of interstellar matter. To achieve this objective, I will improve our chemical model by adding new processes on grain surfaces relevant under the diffuse medium conditions. This upgraded gas-grain model will be coupled to 3D dynamical models of the formation of dense clouds from diffuse medium and of protoplanetary disks from dense clouds. The computed chemical composition will also be used with 3D radiative transfer codes to study the chemical tracers of the physics of protoplanetary disk formation. The robustness of the model predictions will be studied with sensitivity analyses. Finally, model results will be confronted to observations to address some of the current challenges.

1 166 231 €

Start date: 2013-09-01, End date: 2018-08-31

The sub-cellular processes that control the most critical aspects of life occur in three-dimensions (3D), and are intrinsically dynamic. While super-resolution microscopy has revolutionized cellular imaging in recent years, our current capability to observe the dynamics of life on the nanoscale is still extremely limited, due to inherent trade-offs between spatial, temporal and spectral resolution using existing approaches. We propose to develop and demonstrate an optical microscopy methodology that would enable live sub-cellular observation in unprecedented detail. Making use of multicolor 3D point-spread-function (PSF) engineering, a technique I have recently developed, we will be able to simultaneously track multiple markers inside live cells, at high speed and in five-dimensions (3D, time, and color). Multicolor 3D PSF engineering holds the potential of being a uniquely powerful method for 5D tracking. However, it is not yet applicable to live-cell imaging, due to significant bottlenecks in optical engineering and signal processing, which we plan to overcome in this project. Importantly, we will also demonstrate the efficacy of our method using a challenging biological application: real-time visualization of chromatin dynamics - the spatiotemporal organization of DNA. This is a highly suitable problem due to its fundamental importance, its role in a variety of cellular processes, and the lack of appropriate tools for studying it. The project is divided into 3 aims: 1. Technology development: diffractive-element design for multicolor 3D PSFs. 2. System design: volumetric tracking of dense emitters. 3. Live-cell measurements: chromatin dynamics. Looking ahead, here we create the imaging tools that pave the way towards the holy grail of chromatin visualization: dynamic observation of the 3D positions of the ~3 billion DNA base-pairs in a live human cell. Beyond that, our results will be applicable to numerous 3D micro/nanoscale tracking applications.

1 802 500 €

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

"The twin concepts of sustainability and conservation that are so pivotal within current debates regarding economic development and biodiversity protection both contain an inherent temporal dimension, since both refer to the need to balance short-term gains with long-term resource maintenance. Proponents of resilience theory and of development based on ‘indigenous knowledge’ have thus argued for the necessity of including archaeological, historical and palaeoenvironmental components within development project design. Indeed, some have argued that archaeology should lead these interdisciplinary projects on the grounds that it provides the necessary time depth and bridges the social and natural sciences. The project proposed here accepts this logic and endorses this renewed contemporary relevance of archaeological research. However, it also needs to be admitted that moving beyond critiques of the misuse of historical data presents significant hurdles. When presenting results outside the discipline, for example, archaeological projects tend to downplay the poor archaeological visibility of certain agricultural practices, and computer models designed to test sustainability struggle to adequately account for local cultural preferences. This field will therefore not progress unless there is a frank appraisal of archaeology’s strengths and weaknesses. This project will provide this assessment by employing a range of established and groundbreaking archaeological and modelling techniques to examine the development of two east Africa agricultural systems: one at the abandoned site of Engaruka in Tanzania, commonly seen as an example of resource mismanagement and ecological collapse; and another at the current agricultural landscape in Konso, Ethiopia, described by the UN FAO as one of a select few African “lessons from the past”. The project thus aims to assess the sustainability of these systems, but will also assess the role archaeology can play in such debates worldwide."

1 196 701 €

Start date: 2014-02-01, End date: 2018-01-31

One of the most exciting research questions within archaeology is that of the peopling of Australasia by at least c.50,000 years ago. This represents some of the earliest evidence of modern human colonization outside Africa, yet, even at the greatest sea-level lowstand, this migration would have involved seafaring. It is the maritime nature of this dispersal which makes it so important to questions of technological, cognitive and social human development. These issues have traditionally been the preserve of archaeologists, but with a multidisciplinary approach that embraces cutting-edge marine geophysical, hydrodynamic and archaeogenetic analyses, we now have the opportunity to examine the When, Where, Who and How of the earliest seafaring in world history. The voyage from Sunda (South East Asia) to Sahul (Australasia) provides evidence for the earliest ‘open water’ crossing in the world. A combination of the sparse number of early archaeological finds and the significant changes in the palaeolandscape and submergence of the broad north western Australian continental shelf, mean that little is known about the routes taken and what these crossings may have entailed. This project will combine research of the submerged palaeolandscape of the continental shelf to refine our knowledge of the onshore/offshore environment, identify potential submerged prehistoric sites and enhance our understanding of the palaeoshoreline and tidal regime. This will be combined with archaeogenetic research targeting mtDNA and Y-chromosome data to resolve questions of demography and dating. For the first time this project takes a truly multidisciplinary approach to address the colonization of Sahul, providing an unique opportunity to tackle some of the most important questions about human origins, the relationship between humans and the changing environment, population dynamics and migration, seafaring technology, social organisation and cognition.

1 134 928 €

Start date: 2018-02-01, End date: 2023-01-31

Nanowires based on group III–nitride semiconductors exhibit outstanding potential for emerging applications in energy-efficient lighting, optoelectronics and solar energy harvesting. Nitride nanowires, tailored at the nanoscale, should overcome many of the challenges facing conventional planar nitride materials, and also add extraordinary new functionality to these materials. However, progress towards III–nitride nanowire devices has been hampered by the challenges in quantifying nanowire electrical properties using conventional contact-based measurements. Without reliable electrical transport data, it is extremely difficult to optimise nanowire growth and device design. This project aims to overcome this problem through an unconventional approach: advanced contact-free electrical measurements. Contact-free measurements, growth studies, and device studies will be cross-correlated to provide unprecedented insight into the growth mechanisms that govern nanowire electronic properties and ultimately dictate device performance. A key contact-free technique at the heart of this proposal is ultrafast terahertz conductivity spectroscopy: an advanced technique ideal for probing nanowire electrical properties. We will develop new methods to enable the full suite of contact-free (including terahertz, photoluminescence and cathodoluminescence measurements) and contact-based measurements to be performed with high spatial resolution on the same nanowires. This will provide accurate, comprehensive and cross-correlated feedback to guide growth studies and expedite the targeted development of nanowires with specified functionality. We will apply this powerful approach to tailor nanowires as photoelectrodes for solar photoelectrochemical water splitting. This is an application for which nitride nanowires have outstanding, yet unfulfilled, potential. This project will thus harness the true potential of nitride nanowires and bring them to the forefront of 21st century technology.

1 499 195 €

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

A significant advance in the field of development has been the appreciation that radial glial cells are progenitors and give birth to neurons in the brain. In order to advance this exciting area of biology, we need approaches that combine structural and functional studies of these cells. This is reflected by the emerging realisation that dynamic interactions involving radial glia may be critical for the regulation of their proliferative behaviour. It has been observed that radial glia experience transient elevations in intracellular Ca2+ but the nature of these signals, and the information that they convey, is not known. The inability to observe these cells in vivo and over the course of their development has also meant that basic questions remain unexplored. For instance, how does the behaviour of a radial glial cell at one point in development, influence the final identity of its progeny? I propose to build a research team that will capitalise upon methods we have developed for observing individual radial glia and their progeny in an intact vertebrate nervous system. The visual system of Xenopus Laevis tadpoles offers non-invasive optical access to the brain, making time-lapse imaging of single cells feasible over minutes and weeks. The system s anatomy lends itself to techniques that measure the activity of the cells in a functional sensory network. We will use this to examine signalling mechanisms in radial glia and how a radial glial cell s experience influences its proliferative behaviour and the types of neuron it generates. We will also examine the interactions that continue between a radial glial cell and its daughter neurons. Finally, we will explore the relationships that exist within neuronal progeny derived from a single radial glial cell.

1 284 808 €

Start date: 2010-02-01, End date: 2015-01-31

In a changing world, one hallmark feature of human behaviour is the ability to learn about the statistics of the environment and use this prior information for action selection. Knowing about a forthcoming event allows for adjusting our actions pre-emptively, which can optimize survival. This proposal studies how the human brain learns about the uncertainty in the environment, and how this leads to flexible and efficient action selection. I hypothesise that the accumulation of evidence for future movements through learning reflects a fundamental organisational principle for action control. This explains widely distributed perceptual-, learning-, decision-, and movement-related signals in the human brain. However, little is known about the concerted interplay between brain regions in terms of effective connectivity which is required for flexible behaviour. My proposal seeks to shed light on this unresolved issue. To this end, I will use i) a multi-disciplinary neuroimaging approach, together with model-based analyses and Bayesian model comparison, adapted to human reaching behaviour as occurring in daily life; and ii) two novel approaches for testing effective connectivity: dynamic causal modelling (DCM) and concurrent transcranial magnetic stimulation-functional magnetic resonance imaging. My prediction is that action selection relies on effective connectivity changes, which are a function of the prior information that the brain has to learn about. If true, this will provide novel insight into the human ability to select actions, based on learning about the uncertainty which is inherent in contextual information. This is relevant for understanding action selection during development and ageing, and for pathologies of action such as Parkinson s disease or stroke.

1 341 805 €

Start date: 2011-06-01, End date: 2016-05-31

The colonisation of Europe by anatomically modern humans (AMHs) ca. 45,000 years before present (BP) and the transition to farming ca. 8,000 BP are two major events in human prehistory. Both events involved certain cultural and biological adaptations, technological innovations, and behavioural plasticity which are unique to our species. The reconstruction of these processes and the causality between them has so far remained elusive due to technological, methodological and logistical complexities. Major developments in our understanding of the anthropology of the Upper Palaeolithic, Mesolithic and Neolithic, and advances in ancient DNA (aDNA) technology and chronometric methods now allow us to assess in sufficient resolution the interface between these evolutionary processes, and changes in human culture and behaviour. The proposed research will investigate the complex interface between the morphological, genetic, behavioural, and cultural factors that shaped the population history of European AMHs. The PI s interdisciplinary expertise in these areas, his access to and experience of relevant skeletal collections, and his ongoing European collaborations will allow significant progress in addressing these fundamental questions. The approach taken will include (a) the collection of bioarchaeological, aDNA, stable isotope (for the analysis of ancient diet) and radiometric data on 500 skeletons from key sites/phases in Europe and western Anatolia, and (b) the application of existing and novel aDNA, bioarchaeological and simulation methodologies. This research will yield results that transform our current understanding of major demographic and evolutionary processes and will place Europe at the forefront of anthropological biological and genetic research.

1 088 386 €

Start date: 2011-01-01, End date: 2015-12-31

The spread of farming practices in various parts of the world had a marked influence on how humans live today and how we are distributed around the globe. Around 10,000 years ago, warmer conditions lead to population increases, coinciding with the invention of farming in several places around the world. Archaeological evidence attest to the spread of these practices to neighboring regions. In many cases this lead to whole continents being converted from hunter-gatherer to farming societies. It is however difficult to see from archaeological records if only the farming culture spread to other places or whether the farming people themselves migrated. Investigating patterns of genetic variation for farming populations and for remaining hunter-gatherer groups can help to resolve questions on population movements co-occurring with the spread of farming practices. It can further shed light on the routes of migration and dates when migrants arrived. The spread of farming to Europe has been thoroughly investigated in the fields of archaeology, linguistics and genetics, while on other continents these events have been less investigated. In Africa, mainly linguistic and archaeological studies have attempted to elucidate the spread of farming and herding practices. I propose to investigate the movement of farmer and pastoral groups in Africa, by typing densely spaced genome-wide variant positions in a large number of African populations. The data will be used to infer how farming and pastoralism was introduced to various regions, where the incoming people originated from and when these (potential) population movements occurred. Through this study, the Holocene history of Africa will be revealed and placed into a global context of migration, mobility and cultural transitions. Additionally the study will give due credence to one of the largest Neolithic expansion events, the Bantu-expansion, which caused a pronounced change in the demographic landscape of the African continent

1 500 000 €

Start date: 2017-11-01, End date: 2022-10-31

The establishment of farming is a pivotal moment in human history, setting the stage for the emergence of class-based society and urbanization. Monolithic views of the nature and development of early agriculture, however, have prevented clear understanding of how exactly farming fuelled, shaped and sustained the emergence of complex societies. A breakthrough in archaeological approach is needed to determine the actual roles of farming in the emergence of social complexity. The methodology required must push beyond conventional interpretation of the most direct farming evidence – archaeobotanical remains of crops and associated arable weeds – to reconstruct not only what crops were grown, but also how, where and why farming was practised. Addressing these related aspects, in contexts ranging from early agricultural villages to some of the world’s earliest cities, would provide the key to unraveling the contribution of farming to the development of lasting social inequalities. The research proposed here takes a new interdisciplinary approach combining archaeobotany, plant stable isotope chemistry and functional plant ecology, building on groundwork laid in previous research by the applicant. These approaches will be applied to two relatively well researched areas, western Asia and Europe, where a series of sites that chart multiple pathways to early complex societies offer rich plant and other bioarchaeological assemblages. The proposed project will set a wholly new standard of insight into early farming and its relationship with early civilization, facilitating similar approaches in other parts of the world and the construction of comparative perspectives on the global significance of early agriculture in social development.

1 199 647 €

Start date: 2013-02-01, End date: 2017-01-31

AncientAdhesives addresses the most crucial problem in Palaeolithic archaeology: How to reliably infer cognitively complex behaviour in the deep past. To study the evolution of Neandertal and modern human cognitive capacities, certain find categories are taken to reflect behavioural and thus cognitive complexitye.g. Among these are art objects, personal ornaments and complex technology. Of these technology is best-suited to trace changing behavioural complexity, because 1) it is the least vulnerable to differential preservation, and 2) technological behaviours are present throughout the history of our genus. Adhesives are the oldest examples of highly complex technology. They are also known earlier from Neandertal than from modern human contexts. Understanding their technological complexity is thus essential to resolve debates on differences in cognitive complexity of both species. However, currently, there is no agreed-upon method to measure technological complexity. The aim of AncientAdhesives is to create the first reliable method to compare the complexity of Neandertal and modern human technologies. This is achieved through three main objectives: 1. Collate the first comprehensive body of knowledge on adhesives, including ethnography, archaeology and (experimental) material properties (e.g. preservation, production). 2. Develop a new archaeological methodology by modifying industrial process modelling for archaeological applications. 3. Evaluate the development of adhesive technological complexity through time and across species using a range of explicit complexity measures. By analysing adhesives, it is possible to measure technological complexity, to identify idiosyncratic behaviours and to track adoption and loss of complex technological know-how. This represents a step-change in debates about the development of behavioural complexity and differences/similarities between Neanderthals and modern humans.

1 499 926 €

Start date: 2019-02-01, End date: 2024-01-31

Within a 12 month period, 20% of adults will meet criteria for one or more clinical anxiety disorders (ADs). These disorders are hugely disruptive, placing an emotional burden on individuals and their families. While both cognitive behavioural therapy and pharmacological treatment are widely viewed as effective strategies for managing ADs, systematic review of the literature reveals that only 30–45% of patients demonstrate a marked response to treatment (anxiety levels being reduced into the nonaffected range). In addition, a significant proportion of initial responders relapse after treatment is discontinued. There is hence a real and marked need to improve upon current approaches to AD treatment. One possible avenue for improving response rates is through optimizing initial treatment selection. Specifically, it is possible that certain individuals might respond better to cognitive interventions while others might respond better to pharmacological treatment. Recently it has been suggested that there may be two or more distinct biological pathways disrupted in anxiety. If this is the case, then specification of these pathways may be an important step in predicting which individuals are likely to respond to which treatment. Few studies have focused upon this issue and, in particular, upon identifying neural markers that might predict response to cognitive (as opposed to pharmacological) intervention. The proposed research aims to address this. Specifically, it tests the hypothesis that there are at least two mechanisms disrupted in ADs, one entailing amygdala hyper-responsivity to cues that signal threat, the other impoverished recruitment of frontal regions that support cognitive and emotional regulation. Two series of functional magnetic resonance imaging experiments will be conducted. These will investigate differences in amygdala and frontal function during (a) attentional processing and (b) fear conditioning. Initial clinical experiments will investigate whether Generalised Anxiety Disorder and Specific Phobia involve differing degrees of disruption to frontal versus amygdala function during these tasks. This work will feed into training studies, the goal being to characterize AD patient subgroups that benefit from cognitive training.

1 708 407 €

Start date: 2011-04-01, End date: 2016-08-31

Novel sophisticated technologies that exploit the laws of quantum physics form a cornerstone for the future well-being, economic growth and security of Europe. Here photonic devices have gained a prominent position because the absorption, emission, propagation or storage of a photon is a process that can be harnessed at a fundamental level and render more practical ways to use light for such applications. However, the interaction of light with single quantum systems under ambient conditions is typically very weak and difficult to control. Furthermore, there are quantum phenomena occurring in matter at nanometer length scales that are currently not well understood. These deficiencies have a direct and severe impact on creating a bridge between quantum physics and photonic device technologies. aQUARiUM, precisely address the issue of controlling and enhancing the interaction between few photons and rolled-up nanostructures with ability to be deployed in practical applications. With aQUARiUM, we will take epsilon (permittivity)-near-zero (ENZ) metamaterials into quantum nanophotonics. To this end, we will integrate quantum emitters with rolled-up waveguides, that act as ENZ metamaterial, to expand and redefine the range of light-matter interactions. We will explore the electromagnetic design freedom enabled by the extended modes of ENZ medium, which “stretches” the effective wavelength inside the structure. Specifically, aQUARiUM is built around the following two objectives: (i) Enhancing light-matter interactions with single emitters (Enhance) independent of emitter position. (ii) Enabling collective excitations in dense emitter ensembles (Collect) coherently connect emitters on nanophotonic devices to obtain coherent emission. aQUARiUM aims to create novel light-sources and long-term entanglement generation and beyond. The envisioned outcome of aQUARiUM is a wholly new photonic platform applicable across a diverse range of areas.

1 499 431 €

Start date: 2019-01-01, End date: 2023-12-31

The Hippocratic Aphorisms have exerted a singular influence over generations of physicians both in the East and in the West. Galen (d. c. 216) produced an extensive commentary on this text, as did other medical authors writing in Greek, Latin, Arabic, and Hebrew. The Arabic tradition is particularly rich, with more than a dozen commentaries extant in over a hundred manuscripts. These Arabic commentaries did not merely contain scholastic debates, but constituted important venues for innovation and change. Moreover, they impacted on medical practice, as the Aphorisms were so popular that both doctors and their patients knew them by heart. Despite their importance for medical theory and practice, previous scholarship on them has barely scratched the surface. Put succinctly, the present project breaks new ground by conducting an in-depth study of this tradition through a highly innovative methodology: it approaches the available evidence as a corpus, to be constituted electronically, and to be analysed in an interdisciplinary way. We propose to survey the manuscript tradition of the Arabic commentaries on the Hippocratic Aphorisms, beginning with Ḥunayn ibn ʾIsḥāq’s Arabic translation of Galen’s commentary. On the basis of this philological survey that will employ a new approach to stemmatics, we shall produce provisional electronic XML editions of the commentaries. These texts will constitute the corpus, some 600,000 words long, that we shall investigate through the latest IT tools to address a set of interdisciplinary problems: textual criticism of the Greek sources; Graeco-Arabic translation technique; methods of quotation; hermeneutic procedures; development of medical theory; medical practice; and social history of medicine. Both in approach and scope, the project will bring about a paradigm shift in our study of exegetical cultures in Arabic, and the role that commentaries played in the transmission and transformation of scientific knowledge.

1 499 968 €

Start date: 2012-02-01, End date: 2017-07-31

Brain consists of two basic cell types – neurons and glia. However, the study of glia in brain function has traditionally been neglected in favor of their more “illustrious” counter-parts – neurons that are classed as the computational units of the brain. Glia have usually been classed as “brain glue” - a supportive matrix on which neurons grow and function. However, recent evidence suggests that glia are more than passive “glue” and actually modulate neuronal function. This has lead to the proposal of a “tripartite synapse”, which recognizes pre- and postsynaptic neuronal elements and glia as a unit. However, what is still lacking is rudimentary information on how these cells actually function in situ. Here we propose taking a “bottom-up” approach, by identifying the molecules (and interactions) that control glial function in situ. This is complicated by the fact that glia show profound changes when placed into culture. To circumvent this, we will use recently developed cell sorting techniques, to rapidly isolate genetically marked glial cells from brain – which can then be analyzed using advanced biochemical and physiological techniques. The long-term aim is to identify proteins that can be “tagged” using transgenic technologies to allow protein function to be studied in real-time in vivo, using sophisticated imaging techniques. Given the number of proteins that may be identified we envisage developing new methods of generating transgenic animals that provide an attractive alternative to current “state-of-the art” technology. The importance of studying glial function is given by the fact that every major brain pathology shows reactive gliosis. In the time it takes to read this abstract, 5 people in the EU will have suffered a stroke – not to mention those who suffer other forms of neurotrauma. Thus, understanding glial function is not only critical to understanding normal brain function, but also for relieving the burden of severe neurological injury and disease

1 490 168 €

Start date: 2012-01-01, End date: 2016-12-31

Despite considerable efforts aimed at prevention and treatment, the prevalence of obesity and type 2 diabetes has increased at an alarming rate worldwide over recent decades. Given the urgent need to develop safe and efficient anti-obesity drugs, the scientific community has to intensify efforts to better understand the mechanisms involved in the pathogenesis of obesity. Based on human genome-wide association studies and targeted mouse mutagenesis models, it has recently emerged that the brain controls most aspects of systemic metabolism and that obesity may be a brain disease. I have recently shown that like neurons, astrocytes also respond to circulating nutrients, and they cooperate with neurons to efficiently regulate energy metabolism. So far, the study of brain circuits controlling energy balance has focused on neurons, ignoring the presence and role of astrocytes. Importantly, our studies were the first to describe that exposure to a high-fat, highsugar (HFHS) diet triggers hypothalamic astrogliosis prior to significant body weight gain, indicating a potentially important role in promoting obesity. Overall, my recent findings suggest a novel model in which astrocytes are actively involved in the central nervous system (CNS) control of metabolism, likely including active crosstalk between astrocytes and neurons. To test this hypothetical model, I propose to develop a functional understanding of astroglia-neuronal communication in the CNS control of metabolism focusing on: 1) dissecting the ability of astrocytes to release gliotransmitters to neurons, 2) assessing how astrocytes respond to neuronal activity, and 3) determining if HFHS-induced astrogliosis interrupts this crosstalk and contributes to the development of obesity and type 2 diabetes. These studies aim to uncover the molecular underpinnings of astrocyte-neuron inputs regulating metabolism in health and disease so as to inspire and enable novel therapeutic strategies to fight diabetes and obesity.

1 499 938 €

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

At every moment in time, the brain receives a vast amount of sensory information about the environment. This makes attention, the process by which we select currently relevant stimuli for processing and ignore irrelevant input, a fundamentally important brain function. Studies in primates have yielded a detailed description of how attention to a stimulus modifies the responses of neuronal ensembles in visual cortex, but how this modulation is produced mechanistically in the circuit is not well understood. Neuronal circuits comprise a large variety of neuron types, and to gain mechanistic insights, and to treat specific diseases of the nervous system, it is crucial to characterize the contribution of different identified cell types to information processing. Inhibition supplied by a small yet highly diverse set of interneurons controls all aspects of cortical function, and the central hypothesis of this proposal is that differential modulation of genetically-defined interneuron types is a key mechanism of attention in visual cortex. To identify the interneuron types underlying attentional modulation and to investigate how this, in turn, affects computations in the circuit we will use an innovative multidisciplinary approach combining genetic targeting in mice with cutting-edge in vivo 2-photon microscopy-based recordings and selective optogenetic manipulation of activity. Importantly, a key set of experiments will test whether the observed neuronal mechanisms are causally involved in attention at the level of behavior, the ultimate readout of the computations we are interested in. The expected results will provide a detailed, mechanistic dissection of the neuronal basis of attention. Beyond attention, selection of different functional states of the same hard-wired circuit by modulatory input is a fundamental, but poorly understood, phenomenon in the brain, and we predict that our insights will elucidate similar mechanisms in other brain areas and functional contexts.

1 466 505 €

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

Long-term studies of free-living vertebrate populations have proved a rich resource for understanding evolutionary and ecological processes, because individuals’ life histories can be measured by tracking them from birth/hatching through to death. In recent years the ‘animal model’ has been applied to pedigreed long-term study populations with great success, dramatically advancing our understanding of quantitative genetic parameters such as heritabilities, genetic correlations and plasticities of traits that are relevant to microevolutionary responses to environmental change. Unfortunately, quantitative genetic approaches have one major drawback – they cannot identify the actual genes responsible for genetic variation. Therefore, it is impossible to link evolutionary responses to a changing environment to molecular genetic variation, making our picture of the process incomplete. Many of the best long-term studies have been conducted in passerine birds. Unfortunately genomics resources are only available for two model avian species, and are absent for bird species that are studied in the wild. I will fill this gap by exploiting recent advances in genomics technology to sequence the entire transcriptome of the longest running study of wild birds – the great tit population in Wytham Woods, Oxford. Having identified most of the sequence variation in the great tit transcriptome, I will then genotype all birds for whom phenotype records and blood samples are available This will be, by far, the largest phenotype-genotype dataset of any free-living vertebrate population. I will then use gene mapping techniques to identify genes and genomic regions responsible for variation in a number of key traits such as lifetime recruitment, clutch size and breeding/laying date. This will result in a greater understanding, at the molecular level, how microevolutionary change can arise (or be constrained).

1 560 770 €

Start date: 2008-10-01, End date: 2014-06-30

The project will examine the histories of yoga, ayurveda and rasashastra (Indian alchemy and iatrochemistry) from the tenth century to the present, focussing on the disciplines' health, rejuvenation and longevity practices. The goals of the project are to reveal the entanglements of these historical traditions, and to trace the trajectories of their evolution as components of today's global healthcare and personal development industries. Our hypothesis is that practices aimed at achieving health, rejuvenation and longevity constitute a key area of exchange between the three disciplines, preparing the grounds for a series of important pharmaceutical and technological innovations and also profoundly influencing the discourses of today's medicalized forms of globalized yoga as well as of contemporary institutionalized forms of ayurveda and rasashastra. Drawing upon the primary historical sources of each respective tradition as well as on fieldwork data, the research team will explore the shared terminology, praxis and theory of these three disciplines. We will examine why, when and how health, rejuvenation and longevity practices were employed; how each discipline’s discourse and practical applications relates to those of the others; and how past encounters and cross-fertilizations impact on contemporary health-related practices in yogic, ayurvedic and alchemists’ milieus. The five-year project will be based at the Department of South Asian, Tibetan and Buddhist Studies at Vienna University and carried out by an international team of 3 post-doctoral researchers. The research will be grounded in the fields of South Asian studies and social history. An international workshop and an international conference will be organized to present and discuss the research results, which will also be published in peer-reviewed journals, an edited volume, and in individual monographs. A project website will provide open access to all research results.

1 416 146 €

Start date: 2015-06-01, End date: 2020-05-31

A new generation of galaxy surveys will soon start measuring the spatial distribution of millions of galaxies over a broad range of redshifts, offering an imminent opportunity to discover new physics. A detailed comparison of these measurements with theoretical models of galaxy clustering may reveal a new fundamental particle, a breakdown of General Relativity, or a hint on the nature of cosmic acceleration. Despite a large progress in the analytic treatment of structure formation in recent years, traditional clustering models still suffer from large uncertainties. This limits cosmological analyses to a very restricted range of scales and statistics, which will be one of the main obstacles to reach a comprehensive exploitation of future surveys. Here I propose to develop a novel simulation--based approach to predict galaxy clustering. Combining recent advances in computational cosmology, from cosmological N--body calculations to physically-motivated galaxy formation models, I will develop a unified framework to directly predict the position and velocity of individual dark matter structures and galaxies as function of cosmological and astrophysical parameters. In this formulation, galaxy clustering will be a prediction of a set of physical assumptions in a given cosmological setting. The new theoretical framework will be flexible, accurate and fast: it will provide predictions for any clustering statistic, down to scales 100 times smaller than in state-of-the-art perturbation--theory--based models, and in less than 1 minute of CPU time. These advances will enable major improvements in future cosmological constraints, which will significantly increase the overall power of future surveys maximising our potential to discover new physics.

1 484 240 €

Start date: 2017-09-01, End date: 2022-08-31

BEACON aims at performing an ambitious multi-disciplinary (optical, radio astronomy and theoretical physics) study to enable a fundamentally improved understanding of gravitation and space-time. For almost a century Einstein's general relativity has been the last word on gravity. However, superstring theory predicts new gravitational phenomena beyond relativity. In this proposal I will attempt to detect these new phenomena, with a sensitivity 20 times better than state-of-the-art attempts. A successful detection would take physics beyond its current understanding of the Universe. These new gravitational phenomena are emission of dipolar gravitational waves and the violation of the strong equivalence principle (SEP). I plan to look for them by timing newly discovered binary pulsars. I will improve upon the best current limits on dipolar gravitational wave emission by a factor of 20 within the time of this proposal. I also plan to develop a test of the Strong Equivalence Principle using a new pulsar/main-sequence star binary. The precision of this test is likely to surpass the current best limits within the time frame of this proposal and then keep improving indefinitely with time. This happens because this is the cleanest gravitational experiment ever carried out. In order to further these goals, I plan to build the ultimate pulsar observing system. By taking advantage of recent technological advances in microwave engineering (particularly sensitive ultra-wide band receivers) digital electronics (fast analogue-to-digital converters and digital spectrometers) and computing, my team and me will be able to greatly improve the sensitivity and precision for pulsar timing experiments and exploit the capabilities of modern radio telescopes to their limits. Pulsars are the beacons that will guide me in these new, uncharted seas.

1 892 376 €

Start date: 2011-09-01, End date: 2016-08-31

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

The proposed project offers a new, pan-European intellectual history of the political imagination in the interwar period that places the demise of historicism and progressivism – and the emerging anti-teleological visions of time – at the center of some of its most innovative ethical, political and methodological pursuits. It argues that only a distinctively cross-disciplinary and European narrative can capture the full ramifications and legacies of a fundamental rupture in thought conventionally, yet inadequately confined to the German cultural space and termed “anti-historicism”. It innovates narratively by exploring politically and theoretically interlaced reinventions of temporality across and between different disciplines (theology, jurisprudence, classical studies, literary theory, linguistics, sociology, philosophy), as well as other creative fields. It experiments methodologically by reconstructing the dynamics of political thought prosopographically, through intellectual groupings at the forefront of the scholarly and political debates of the period. It challenges the sufficiency of the standard focus in interwar intellectual history on one or two, at most three (usually “Western” European) national contexts by following out the interactions of these groupings in France, Britain, Germany, Russia, Czechoslovakia, and Romania – groupings whose members frequently moved across national contexts. What were the political languages encoded in the reinventions of time, and vice versa – how were political aims translated into and advanced through theoretical innovation? How did these differ in different national contexts, and why? What are the fragmented legacies of this rupture, disbursed in and through the philosophical, methodological and political dicta and dogmas that rooted themselves in post-1945 thought? This project provides the first comprehensive answer to these fundamental questions about the intellectual identity of Europe and its historicities.

1 425 000 €

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

We are largely unaware of our own motives. Understanding our motives can be reduced to knowing how we form goals and these goals translate into behavior. Goals can be defined as pleasurable situations that we particularly value and that we intend to reach. Recent investigation in the emerging field of neuro-economics has put forward a neuronal network constituting a brain valuation system (BVS). We wish to build a more comprehensive account of motivational processes, investigating not only valuation and choice but also effort (how much energy we would spend to attain a goal). More specifically, our aims are to better describe 1) how the brain assigns values to various objects and actions, 2) how values depend on parameters such as reward magnitude, probability, delay and cost, 3) how values are affected by social contexts, 4) how values are modified through learning and 5) how values influence the brain systems (perceptual, cognitive and motor) that underpin behavioral performance. To these aims, we would combine three approaches: 1) human cognitive neuroscience, which is central as we ultimately wish to understand ourselves, as well as human pathological conditions where motivation is either deficient (apathy) or out of control (compulsion), 2) primate neurophysiology, which is essential to describe information processing at the single-unit level and to derive causality by observing behavioral consequences of brain manipulations, 3) computational modeling, which is mandatory to link quantitatively the different descriptions levels (single-unit recordings, local field potentials, regional BOLD signal, vegetative manifestations and motor outputs). A bayesian framework will be developed to infer from experimental measures the subjects prior beliefs and value functions. We believe that our team, bringing together three complementary perspectives on motivation within a clinical environment, would represent a unique education and research center in Europe.

1 346 000 €

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

Over the past decades, silicon became the most used material for electronic, however its indirect band gap limits its use for optics and optoelectronics. As a result alternatives semiconductor such as III-V and II-VI materials are used to address a broad range of complementary application such as LED, laser diode and photodiode. However in the infrared (IR), the material challenge becomes far more complex. New IR applications, such as flame detection or night car driving assistance are emerging and request low cost detectors. Current technologies, based on epitaxially grown semiconductors are unlikely to bring a cost disruption and organic electronics, often viewed as the alternative to silicon based materials is ineffective in the mid-IR. The blackQD project aims at transforming colloidal quantum dots (CQD) into the next generation of active material for IR detection. CQD are attracting a high interest because of their size tunable optical features and next challenges is their integration in optoelectronic devices and in particular for IR features. The project requires a combination of material knowledge, with clean room nanofabrication and IR photoconduction which is unique in Europe. I organize blackQD in three mains parts. The first part relates to the growth of mercury chalcogenides nanocrystals with unique tunable properties in the mid and far-IR. To design devices with enhanced properties, more needs to be known on the electronic structure of these nanomaterials. In part II, I propose to develop original methods to probe static and dynamic aspects of the electronic structure. Finally the main task of the project relates to the design of a new generation of transistors and IR detectors. I propose several geometries of demonstrator which for the first time integrate from the beginning the colloidal nature of the CQD and constrain of IR photodetection. The project more generally aims to develop a tool box for the design of the next generation of low cost IR.

1 499 903 €

Start date: 2018-02-01, End date: 2023-01-31

We and others have recently delineated the molecular architecture of a new feedback pathway in brain synapses, which operates as a synaptic circuit breaker. This pathway is supposed to use a group of lipid messengers as retrograde synaptic signals, the so-called endocannabinoids. Although heterogeneous in their chemical structures, these molecules along with the psychoactive compound in cannabis are thought to target the same effector in the brain, the CB1 receptor. However, the molecular catalog of these bioactive lipids and their metabolic enzymes has been expanding rapidly by recent advances in lipidomics and proteomics raising the possibility that these lipids may also serve novel, yet unidentified physiological functions. Thus, the overall aim of our research program is to define the molecular and anatomical organization of these endocannabinoid-mediated pathways and to determine their functional significance. In the present proposal, we will focus on understanding how these novel pathways regulate synaptic and extrasynaptic signaling in hippocampal neurons. Using combination of lipidomic, genetic and high-resolution anatomical approaches, we will identify distinct chemical species of endocannabinoids and will show how their metabolic enzymes are segregated into different subcellular compartments in cell type- and synapse-specific manner. Subsequently, we will use genetically encoded gain-of-function, loss-of-function and reporter constructs in imaging experiments and electrophysiological recordings to gain insights into the diverse tasks that these new pathways serve in synaptic transmission and extrasynaptic signal processing. Our proposed experiments will reveal fundamental principles of intercellular and intracellular endocannabinoid signaling in the brain.

1 638 000 €

Start date: 2009-11-01, End date: 2014-10-31

The brain is composed of a set of areas specialized in specific computations whose outputs need to be transferred to other specialized areas for cognition to emerge. To account for context-dependent behaviors, the information has to be flexibly routed through the fixed anatomy of the brain. The aim of my proposal is to test a general framework for flexible communication between brain areas based on nested oscillations which I recently developed. The general idea is that internally-driven slow oscillations (<20Hz) either set-up or prevent the communication between brain areas. Stimulus-driven gamma oscillations (>30Hz), nested in the slow oscillations, can then be directed to task-relevant areas of the network. I plan to use a multimodal, multi-scale and transversal (human and monkey) approach in experiments manipulating visual processing, attention and memory to test core predictions of my framework. The theoretical approach and the methodological development used in my project will provide the basis for future fundamental and clinical research.

1 333 718 €

Start date: 2017-02-01, End date: 2022-01-31

Aggregates of proteins such as amyloid-beta and alpha-synuclein circulate the extracellular space of the brain (ECS) and are thought to be key players in the development of neurodegenerative diseases. The clearance of these aggregates (among other toxic metabolites) is a fundamental physiological feature of the brain which is poorly understood due to the lack of techniques to study the nanoscale organisation of the ECS. Exciting advances in this field have recently shown that clearance is enhanced during sleep due to a major volume change in the ECS, facilitating the flow of the interstitial fluid. However, this process has only been characterised at a low spatial resolution while the physiological changes occur at the nanoscale. The recently proposed “glymphatic” pathway still remains controversial, as there are no techniques capable of distinguishing between diffusion and bulk flow in the ECS of living animals. Understanding these processes at a higher spatial resolution requires the development of single-molecule imaging techniques that can study the brain in living animals. Taking advantage of the strategies I have recently developed to target single-molecules in the brain in vivo with nanoparticles, we will do “nanoscopy” in living animals. Our proposal will test the glymphatic pathway at the spatial scale in which events happen, and explore how sleep and wake cycles alter the ECS and the diffusion of receptors in neuronal plasma membrane. Overall, BrainNanoFlow aims to understand how nanoscale changes in the ECS facilitate clearance of protein aggregates. We will also provide new insights to the pathological consequences of impaired clearance, focusing on the interactions between these aggregates and their putative receptors. Being able to perform single-molecule studies in vivo in the brain will be a major breakthrough in neurobiology, making possible the study of physiological and pathological processes that cannot be studied in simpler brain preparations.

1 552 948 €

Start date: 2018-12-01, End date: 2023-11-30

Humans and other primates possess an exquisite capacity to grasp and manipulate objects. The seemingly effortless interaction with objects in everyday life is subserved by a number of cortical areas of the visual and the motor system. Recent research has highlighted that dorsal stream areas in the posterior parietal cortex are involved in object processing. Because parietal lesions do not impair object recognition, the encoding of object shape in posterior parietal cortex is considered to be important for the planning of actions towards objects. In order to succesfully grasp an object, the complex pattern of visual information impinging on the retina has to be transformed into a motor plan that can control the muscle contractions. The neural basis of visuomotor transformations necessary for directing actions towards objects, however, has remained largely unknown. This proposal aims to unravel the pathways and mechanisms involved in programming actions towards objects - an essential capacity for our very survival. We envision an integrated approach to study the transformation of visual information into motor commands in the macaque brain, combining functional imaging, single-cell recording, microstimulation and reversible inactivation. Our research efforts will be focussed on parietal area AIP and premotor area F5, two key brain areas for visually-guided grasping. Above all, this proposal will move beyond purely descriptive measurements of neural activity by implementing manipulations of brain activity to reveal behavioral effects and interdependencies of cortical areas. Finally the data obtained in this project will pave the way to use the neural activity recorded in visuomotor areas to act upon the environment by grasping objects by means of a robot hand.

1 499 200 €

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

Global changes in patterns of neuronal activity or brain state are the first phenomenon recorded in the awake human brain (1). Changes in brain state are present in recordings of neocortical activity from mouse to man. It is now thought that changes in brain state are fundamental to normal brain function and neuronal computation. Despite their importance, we have very little idea about the underlying neuronal mechanisms that generate them or their precise impact on neuronal processing and behaviour. In previous work we have characterised brain state changes in a well characterised model for neuroscience research the mouse whisker system. We have recorded changes in the brain state in mouse cortex during whisker movements (2). In this proposal, we aim to use the mouse whisker system further to investigate the mechanisms and functions of changes in brain state. First we will use state of the art techniques to record and manipulate neuronal activity in the awake, behaving mouse to investigate the network and cellular mechanisms involved in generating brain state. Second we will use 2-photon microscopy to investigate the impact of brain state on excitatory and inhibitory synaptic integration in vivo. Finally we will use behaviourally trained mice to measure the impact of brain state changes on sensory perception and behaviour. This proposal will therefore provide fundamental insights into brain function at every step: mechanisms of changes in brain state, how neurons communicate with eachother and how the brain controls sensory perception and behaviour. References 1 Berger H (1929) Archiv für Psychiatrie und Nervenkrankheiten 87:527-570. 2 Poulet JFA, Petersen CC (2008) Nature 454:881-885.

1 463 125 €

Start date: 2011-02-01, End date: 2016-01-31

This project is an interdisciplinary study of the role of indigenous knowledge in the making of science. Situated at the intersection of history and anthropology, its main research objective is to understand the transformation of information and practices of South American indigenous peoples into a body of knowledge that became part of the Western scholarly canon. It aims to explore, by means of a distinctive case-study, how European science is constructed in intercultural settings. This project takes the book Historia Naturalis Brasiliae (HNB), published in 1648 by Piso and Marcgraf, as its central focus. The HNB is the first product of the encounter between early modern European scholarship and South American indigenous knowledge. In an encyclopedic format, it brings together information about the natural world, linguistics, and geography of South America as understood and experienced by indigenous peoples as well as enslaved Africans. Its method of construction embodies the intercultural connections that shaped practices of knowledge production in colonial settings across the globe, and is the earliest example of such in South America. With my research team, I will investigate how indigenous knowledge was appropriated and transformed into European science by focusing on ethnobotanics, ethnozoology, and indigenous material culture. Since the HNB and its associated materials are kept in European museums and archives, this project is timely and relevant in light of the growing concern for the democratization of heritage. The current debate about the societal role of publicly-funded cultural institutions across Europe argues for the importance of multi-vocality in cultural and political processes. This project proposes a more inclusive interpretation and use of the materials in these institutions and thereby sets an example of how European heritage institutions can use their historical collections to reconnect the past with present-day societal concerns.

1 475 565 €

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

The Smart Building Networks (BuildNet) program will develop optimizing controllers capable of coordinating the flow of power to and from large networks of smart buildings in order to offer critical services to the power grid. The network will make use of the thermal storage of the structures and on-site micro generation capabilities of next-generation buildings, as well as the electrical capacity of attached electric vehicles in order to intelligently control the interaction between the network of buildings and the grid. The wide range of electric utility applications, such as wind capacity firming or congestion relief, that will be possible as a result of this coordinated control will in turn allow a significant increase in the percentage of European power generated from destabilizing renewable sources. Technologically, BuildNet will be built around optimization-based or model predictive control (MPC), a paradigm that is ideally suited to the task of incorporating the current network state and forward-looking information into an optimal decision-making process. The project team will develop novel distributed MPC controllers that utilize the flexibility in the consumption, storage and generation of a distributed network of buildings by exploiting the extensive experience of the PI in optimization-based control and MPC for energy efficient buildings. Because of its theoretically grounded optimization-based control approach, holistic view of building systems and connected networks, as well as a future-looking technological scope, BuildNet's outputs will deliver impact and be relevant to researchers and practitioners alike.

1 460 232 €

Start date: 2012-12-01, End date: 2017-11-30

Some of the primary questions in extragalactic astronomy concern the formation and evolution of galaxies in the distant Universe. In particular, little is known about the less luminous (and therefore less massive) galaxy populations, which are currently missed from large observing surveys and could contribute significantly to the overall star formation happening at early times. One way to overcome the current observing limitations prior to the arrival of the future James Webb Space Telescope or the European Extremely Large Telescopes is to use the natural magnification of strong lensing clusters to look at distant sources with an improved sensitivity and resolution. The aim of CALENDS is to build and study in great details a large sample of accurately-modelled, strongly lensed galaxies at high redshift (1<z<5) selected in the fields of massive clusters, and compare them with the more luminous or lower redshift populations. We will develop novel techniques in this process, in order to improve the accuracy of strong-lensing models and precisely determine the mass content of these clusters. By performing a systematic modelling of the cluster sample we will look into the relative distribution of baryons and dark matter as well as the amount of substructure in cluster cores. Regarding the population of lensed galaxies, we will study their global properties through a multiwavelength analysis covering the optical to millimeter domains, including spectroscopic information from MUSE and KMOS on the VLT, and ALMA. We will look for scaling relations between the stellar, gas and dust parameters, and compare them with known relations for lower redshift and more massive galaxy samples. For the most extended sources, we will be able to spatially resolve their inner properties, and compare the results of individual regions with predictions from simulations. We will look into key physical processes: star formation, gas accretion, inflows and outflows, in these distant sources.

1 450 992 €

Start date: 2013-09-01, End date: 2019-08-31

This project will be aimed at obtaining a deeper insight into the physical processes taking place in astrophysical magnetized plasmas. To study these scenarios I will employ different numerical codes as virtual tools that enable me to experiment on computers (virtual labs) with distinct initial and boundary conditions. Among the kind of sources I am interested to consider, I outline the following: Gamma-Ray Bursts (GRBs), extragalactic jets from Active Galactic Nuclei (AGN), magnetars and collapsing stellar cores. A number of important questions are still open regarding the fundamental properties of these astrophysical sources (e.g., collimation, acceleration mechanism, composition, high-energy emission, gravitational wave signature). Additionally, there are analytical issues on the formalism in relativistic dynamics not resolved yet, e.g., the covariant extension of resistive magnetohydrodynamics (MHD). All these problems are so complex that only a computational approach is feasible. I plan to study them by means of relativistic and Newtonian MHD numerical simulations. A principal focus of the project will be to assess the relevance of magnetic fields in the generation, collimation and ulterior propagation of relativistic jets from the GRB progenitors and from AGNs. More generally, I will pursue the goal of understanding the process of amplification of seed magnetic fields until they become dynamically relevant, e.g., using semi-global and local simulations of representative boxes of collapsed stellar cores. A big emphasis will be put on including all the relevant microphysics (e.g. neutrino physics), non-ideal effects (particularly, reconnection physics) and energy transport due to neutrinos and photons to account for the relevant processes in the former systems. A milestone of this project will be to end up with a numerical tool that enables us to deal with General Relativistic Radiation Magnetohydrodynamics problems in Astrophysics.

1 497 000 €

Start date: 2011-03-01, End date: 2017-02-28

In the epoch of Gaia, fundamental stellar properties will be made widely available for large numbers of stars. These properties are expected to unleash a new wave of discovery in the field of astrophysics. But while many properties of stars are measurable, meaningful Helium abundances (Y) remain elusive and as a result fundamental properties are not accurate. Helium enrichment laws, which underpin most stellar properties, link initial Y to initial metallicity, but these relations are very uncertain with gradients (dY/dZ) spanning the range 1 to 3. This uncertainty is the initial Y problem and this is a bottleneck that must be overcome to unleash the true potential of Gaia. Without measurements of initial Y for all stars we need to find alternative observables that trace out the evolution of initial Y. We will search for better tracers using the power of asteroseismology as a calibrator. Asteroseismic measures of Helium will be used to construct a map from observable properties (fundamental, chemical or even dynamical) back to initial Helium. This is a challenge that can only be solved through the use of the latest asteroseismic techniques coupled to a rigorous yet flexible statistical scheme. I am uniquely qualified in the cutting edge methods of asteroseismology and the application of advanced multi-level statistical models. The intersection of these two skill sets will allow me to solve the initial Helium problem. The motivation for a timely solution to this problem could not be stronger. We have just entered an age of large asteroseismic datasets, vast spectroscopic surveys, and the billion star program of Gaia. The next wave of scientific breakthroughs in stellar physics, exoplanetary science, and Galactic archeology will be held back unless accurate fundamental stellar properties are available. We can only produce these accurate properties with a reliable map of stellar Helium.

1 496 203 €

Start date: 2019-04-01, End date: 2024-03-31

The proposed project will significantly improve the insight in the processes that have changed a comet nucleus or asteroid since their formation. These processes typically go along with activity, the observable release of gas and/or dust. Understanding the evolutionary processes of comets and asteroids will allow us to answer the crucial question which aspects of these present-day bodies still provide essential clues to their formation in the protoplanetary disc of the early solar system. Ground-breaking progress in understanding these fundamental questions can now be made thanks to the huge and unprecedented data set returned between 2014 and 2016 by the European Space Agency’s Rosetta mission to comet 67P/Churyumov-Gerasimenko, and by recent major advances in the observational study of active asteroids facilitated by the increased availability of sky surveys and follow-on observations with world-class telescopes. The key aims of this proposal are to - Obtain a unified quantitative picture of the different erosion processes active in comets and asteroids, - Investigate how ice is stored in comets and asteroids, - Characterize the ejected dust (size distribution, optical and thermal properties) and relate it to dust around other stars, - Understand in which respects comet 67P can be considered as representative of a wider sample of comets or even asteroids. We will follow a highly multi-disciplinary approach analyzing data from many Rosetta instruments, ground- and space-based telescopes, and connect these through numerical models of the dust dynamics and thermal properties.

1 484 688 €

Start date: 2018-03-01, End date: 2023-02-28

"Spatially distributed multi-agent networks have been used successfully to model a wide range of natural, social and engineered complex systems, such as animal groups, online communities and electric power grids. In various contexts, it is crucial to introduce control actions into such networks to either achieve desired collective dynamics or test the understanding of the systems’ behavior. However, controlling such systems is extremely challenging due to agents’ complicated sensing, communication and control interactions that are distributed in space. Systematic methodologies to attack this challenge are in urgent need, especially when vast efforts are being made in multiple disciplines to apply the model of complex multi-agent networks. The goal of the project is twofold. First, understand whether a complex multi-agent network can be controlled effectively when the agents can only sense and communicate locally. Second, provide methodologies to implement distributed control in typical spatially distributed complex multi-agent networks. The project requires integrated skills since both rigorous theoretical analysis and novel empirical explorations are necessary. The research methods that I plan to adopt have two distinguishing features. First, I use tools from algebraic graph theory and complex network theory to investigate the impact of network topologies on the systems’ controller performances characterized by mathematical control theory. Second, I utilize a homemade robotic-fish testbed to implement various multi-agent control algorithms. The unique combination of theoretical and empirical studies is expected to lead to breakthroughs in developing an integrated set of principles and techniques to control effectively spatially distributed multi-agent networks. The expected results will make original contributions to control engineering and robotics, and inspire innovative research methods in theoretical biology and theoretical sociology."

1 495 444 €

Start date: 2013-01-01, End date: 2017-12-31

The mammalian brain is assembled from thousands of neuronal cell types that are organized into distinct circuits to perform behaviourally relevant computations. To gain mechanistic insights about brain function and to treat specific diseases of the nervous system it is crucial to understand what these local circuits are computing and how they achieve these computations. By examining the structure and function of a few genetically identified and experimentally accessible neural circuits we plan to address fundamental questions about the functional architecture of neural circuits. First, are cell types assigned to a unique functional circuit with a well-defined function or do they participate in multiple circuits (“multitasking cell types”), adjusting their role depending on the state of these circuits? Second, does a neural circuit perform “a single computation” or depending on the information content of its inputs can it carry out radically different functions? Third, how, among the large number of other cell types, do the cells belonging to the same functional circuit connect together during development? We use the mouse retina as a model system to address these questions. Finally, we will study the structure and function of a specialised neural circuit in the human fovea that enables humans to read. We predict that our insights into the mechanism of multitasking, network switches and the development of selective connectivity will be instructive to study similar phenomena in other brain circuits. Knowledge of the structure and function of the human fovea will open up new opportunities to correlate human retinal function with human visual behaviour and our genetic technologies to study human foveal function will allow us and others to design better strategies for restoring vision for the blind.

1 499 000 €

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

The cerebellum is a critical regulator of motor function, which acts to integrate ongoing body states, sensory inputs and desired outcomes to adjust motor output. This motor control is achieved by a relatively small number of neuron types receiving two main sources of inputs and forming a single output pathway, the axons of Purkinje cells. Although the cerebellum is one of the first structures of the brain to differentiate, it undergoes a prolonged differentiation period such that mature cellular and circuit configuration is achieved only late after birth. Despite the functional importance of this structure, the molecular mechanisms that control type-specific cerebellar neurons generation, differentiation, and circuit assembly are poorly understood and are the topic of the present study. In my research program, I propose to investigate the transcriptional programs that control the generation of distinct subtypes of cerebellar neurons from progenitors, including Purkinje cells, granule cells and molecular layer interneurons (Work Package 1); the diversity of Purkinje cells across cerebellar regions (Work Package 2) and the postnatal differentiation and circuit integration of granule cells and molecular layer interneurons (Work Package 3). The general bases of the approach I propose consist in: i) specifically label cerebellar neuron progenitors and their progeny at sequential developmental time points pre- and post-natally using birthdate-based tagging, ii) FAC-sort these distinct cell types, iii) isolate these cells and identify their transcriptional signatures with single-cell resolution, iv) functionally interrogate top candidate genes and associated transcriptional programs using in vivo gain- and loss-of-function approaches. Together, these experiments aim at deciphering the cell-intrinsic processes controlling cerebellar circuit formation, towards a better understanding of the molecular mechanisms underlying cerebellar function and dysfunction.

1 499 885 €

Start date: 2018-02-01, End date: 2023-01-31

'Coastal Frontiers' will involve the Principal Investigator, Dr Sunil Amrith, and a post-doctoral research assistant, in a study of the Bay of Bengal’s coastal rim from the late-nineteenth century to the present. This project will illuminate the entangled political and ecological history of the coastal arc stretching from India’s southern tip to the edge of the Malay Peninsula. It will combine macro-level perspectives on environmental change, contingent histories of transformations in political sovereignty, and local histories of coastal peoples. It seeks to examine how people have actually inhabited the coastal borderlands of Asia, and the contrasting ways these worlds appear through the eyes of states, or in the minds of coastal ecologists. It will focus on key coastal sites at the frontiers of ecological change, at the frontiers between empires and nations, at the frontiers between terrestrial and maritime law. The project will examine the deeper history of environmental change and political conflict in a region that is now particularly vulnerable to climate change, and at the fault-lines of strategic conflict between India and China. The project will build on the Principal Investigator’s recent work at the frontiers of scholarship in Asian history, through his studies of the links between South and Southeast Asia’s histories of migration and oceanic connection. It is time, now, to root this re-conceptualization of Asia’s regional frontiers in a closer study of environmental change, but to do so in a way that does not lose sight of the experiences and consciousness of individuals. This represents a new departure in scholarship, combining environmental history with the history of transnational flows, bridging insights from the humanities and ecological science. This ambitious project seeks new ways for historians to engage with questions of planetary change, without losing the fine-grained detail and hard archival research that has characterised our discipline.

606 655 €

Start date: 2012-01-01, End date: 2015-06-30

"Magnetism plays a profound role in stars and planets. In the Sun, magnetic fields are ultimately responsible for solar flares and coronal mass ejections that can impact our technological society. Earth's own magnetic field partly shields us from these events, but solar storms can still interrupt satellite communications, disrupt power grids, and pose a danger to astronauts on spacewalks. More generally, magnetic fields partly control the rotational evolution of stars, likely impact the habitability of extrasolar planets, and may modify the sizes and internal structures of low-mass stars and gaseous planets. In all cases, the magnetism is generally thought to arise from a convective dynamo -- but a detailed theoretical understanding of this process, and its influence on the overall evolution of stars and planets, has remained elusive. Particularly fascinating observational puzzles have recently come from the study of low-mass M-dwarf stars: the most numerous type of stars in our galaxy and perhaps the most likely to host habitable planets. We therefore propose to study how stars and sub-stellar objects build magnetic fields using 3-D magnetohydrodynamic simulations, and to quantify the effects of those fields on stellar structure and evolution. Using the Anelastic Spherical Harmonic (ASH) and Compressible Spherical Segment (CSS) codes, we will examine (a) how global magnetic field generation in these stars depends upon parameters like stellar mass, rotation rate, and the presence of a stable core, and (b) how the deep convection and magnetism imprints through (and is shaped by) the near-surface layers of these objects. We will (c) determine the impact of the resulting fields on the convective transport of heat and angular momentum, incorporate our results into state of the art 1-D evolutionary models of stars, and explore the consequences for stellar evolution. Separately, we will (d) develop and maintain a public database of 3-D convective dynamo models."

1 469 070 €

Start date: 2013-12-01, End date: 2018-11-30

This research proposal’s goal is to investigate the role of cortico-hippocampal interactions during the encoding and consolidation of a memory. Current memory consolidation models postulate that memory storage in our brains occurs by a dynamic process- a recent episodic experience is initially encoded in the hippocampus, and during off-line states such as sleep, the encoded memory is gradually transferred to neocortex for long-term storage. One potential neural mechanism by which this could occur is replay, a phenomenon where neural activity patterns in the hippocampus evoked by a previous experience reactivate spontaneously during non-REM sleep, leading to coordinated cortical reactivation. While previous work suggests that hippocampal replay is important for encoding new memories, how memory consolidation is accomplished through cortico-hippocampal interactions is not well understood. This research project has three major aims- 1) examine how cortical feedback influences which spatial trajectory is replayed by the hippocampus, 2) investigate how the hippocampal replay of a behavioural episode modifies cortical circuits, 3) measure the causal role of cortico-hippocampal interactions in consolidating memories. We will record ensemble activity from freely moving rats during an auditory-spatial association task and during post-behavioural sleep sessions. We will focus our ensemble recordings on two brain regions: 1) the dorsal CA1 region of the hippocampus, where the phenomenon of sleep replay has been most extensively examined, and 2) auditory cortex, a region of the brain critical for both auditory perception and long-term memory storage. This work will use behavioral and molecular-genetic techniques in combination with large-scale electrophysiological recordings, to help elucidate the role of cortico-hippocampal interactions in memory encoding and consolidation.

1 500 000 €

Start date: 2015-04-01, End date: 2021-03-31

Neuromodulators such as acetylcholine and dopamine are able to rapidly reprogram neuronal information processing and dynamically change brain states. Degeneration or dysfunction of cholinergic and dopaminergic neurons can lead to neuropsychiatric conditions like schizophrenia and addiction or cognitive diseases such as Alzheimer’s. Neuromodulatory systems control overlapping cognitive processes and often have similar modes of action; therefore it is important to reveal cooperation and competition between different systems to understand their unique contributions to cognitive functions like learning, memory and attention. This is only possible by direct comparison, which necessitates monitoring multiple neuromodulatory systems under identical experimental conditions. Moreover, simultaneous recording of different neuromodulatory cell types goes beyond phenomenological description of similarities and differences by revealing the underlying correlation structure at the level of action potential timing. However, such data allowing direct comparison of neuromodulatory actions are still sparse. As a first step to bridge this gap, I propose to elucidate the unique versus complementary roles of two “classical” neuromodulatory systems, the cholinergic and dopaminergic projection system implicated in various cognitive functions including associative learning and plasticity. First, we will record optogenetically identified cholinergic and dopaminergic neurons simultaneously using chronic extracellular recording in mice undergoing classical and operant conditioning. Second, we will determine the postsynaptic impact of cholinergic and dopaminergic neurons by manipulating them both separately and simultaneously while recording consequential changes in cortical neuronal activity and learning behaviour. These experiments will reveal how major neuromodulatory systems interact to mediate similar or different aspects of the same cognitive functions.

1 499 463 €

Start date: 2017-05-01, End date: 2022-04-30

Over the last 8000 years, the Fertile Crescent of the Near East has seen the emergence of cities, states and empires. Climate fluctuations are generally considered to be a significant factor in these changes because in pre-industrial societies they directly relate to food production and security. In the short term, ‘collapse’ events brought about by extreme weather changes such as droughts have been blamed for declines in population, social complexity and political systems. More broadly, the relationships between environment, settlement and surplus drive most models for the development of urbanism and hierarchical political systems. Studies seeking to correlate social and climatic changes in the past tend either to focus on highly localised analyses of specific sites and surveys or to take a more synthetic overview at much larger, even continental, scales. The CLaSS project will take a ground breaking hybrid approach using archaeological data science (or ‘big data’) to construct detailed, empirical datasets at unprecedented scales. Archaeological settlement data and archaeobotanical data (plant and tree remains) will be collated for the entire Fertile Crescent and combined with climate simulations derived from General Circulation Models using cutting edge techniques. The resulting datasets will represent the largest of their kind ever compiled, covering the period between 8000BP and 2000BP and an area of 600,000km2. Collecting data at this scale will enable us to compare population densities and distribution, subsistence practices and landscape management strategies to investigate the question: What factors have allowed for the differential persistence of societies in the face of changing climatic and environmental conditions? This ambitious project will provide insights into the sustainability and resilience of societies through both abrupt and longer term climate changes, leveraging the deep time perspective only available to archaeology.

1 498 650 €

Start date: 2019-01-01, End date: 2023-12-31

The ClustersXCosmo ERC Starting Grant proposal has the goal of investigating the role of Galaxy Clusters as a cosmological probe and of exploiting the strong synergies between observational cosmology, galaxy formation and fundamental physics related to the tracers of the extreme peaks in the matter density field. In the last decade, astronomical data-sets have started to be widely and quantitatively used by the scientific community to address important physical questions such as: the nature of the dark matter and dark energy components and their evolution; the physical properties of the baryonic matter; the variation of fundamental constants over cosmic time; the sum of neutrino masses; the interplay between the galaxy population and the intergalactic medium; the nature of gravity over megaparsec scales and over cosmic times; the temperature evolution of the Universe. Most of these results are based on well-established geometrical cosmological probes (e.g., galaxies, supernovae, cosmic microwave background). Galaxy clusters provide a complementary and necessary approach, as their distribution as a function of time and observables is sensitive to both the geometrical and the dynamical evolution of the Universe, driven by the growth of structures. Among different cluster surveys, Sunyaev Zel'Dovich effect (SZE) detected catalogs have registered the most dramatic improvement over the last ~5 years, yielding samples extending up to the earliest times these systems appeared. This proposal aims at using a combination of the best available SZE cluster surveys and to interpret them by means of state-of-the-art computational facilities in order to firmly establish the yet controversial role of Galaxy Clusters as a probe for cosmology, fundamental physics and astrophysics. The timely convergence of current and next generation multi-wavelength surveys (DES/SPT/Planck/eRosita/Euclid) will be important to establish the role of Galaxy Clusters as a cosmological tool.

1 230 403 €

Start date: 2017-09-01, End date: 2022-08-31

Infectious diseases have had an intimate history with humans and have shaped our genetic makeup through generating strong selective pressures. Although disease emergence and epidemics occur on a local scale, human interrelationships formed through travel and trade can lead to exchanges of pathogenic communities. While such transfers were common among the interconnected Eurasian and North African cultures throughout most of human history, the rest of the world experienced relative ecological autonomy. The terminal Pleistocene witnessed the colonisation of vast territory on the American continents, after which interactions between New and Old World peoples were limited for millennia by geographical barriers. These ecological worlds collided at the end of the fifteenth century, when improvements in navigation and the discovery of the Americas by Europeans permitted regular contact and plentiful opportunities for biological interchange. The identities of most diseases that played leading roles during this period of exchange are known, though details on the directions of their movement and temporal introductions remain the subject of scholarly debate. The work programme presented here will use an underexplored data source – ancient pathogen genomes – to identify infectious insults in pre- and post-contact New and Old World skeletal series, thus enabling an evaluation of changing disease landscapes at contact. Complementary to this goal, genomic loci for human immunity genes will be interrogated, thus permitting quantitative evaluations of disease adaptation. Ancient molecular data will be acquired through use of the most sensitive and up to date methods in the field of ancient DNA with the aim of bringing diseases not easily seen from skeletal morphology or historical documents to light in clear detail. This will permit an unprecedented resolution of past disease experience and host-pathogen interactions during this dynamic period of global ecological unification.

1 490 043 €

Start date: 2018-12-01, End date: 2023-11-30

A key question in neuroscience is how information is processed by sensory systems to guide behavior. Most of our knowledge about sensory processing is based on presentation of simple isolated stimuli and recording corresponding neural activity in relevant brain areas. Yet sensory stimuli in real life are never isolated and typically not simple. How the brain processes complex stimuli, simultaneously arising from multiple objects is unknown. Our daily experience (as well as well-controlled experiments) shows that only parts of a complex sensory scene can be perceived - we cannot listen to more than one speaker in a party. Importantly, one can easily choose what is important and should be processed and what can be ignored as background. These observations lead to the prevalent hypothesis that feedback projections from ‘higher’ brain areas to more peripheral sensory areas are involved in processing of complex stimuli. However experimental analysis of signals conveyed by feedback projections in behaving animals is scarce. The nature of these signals and how they relate to behavior is unknown. Here I propose a cutting edge approach to directly record feedback signals in the olfactory system of behaving mice. We will use chronically implanted electrodes to record the modulation of olfactory bulb (OB) principal neurons by task related context. Additionally, we will record from piriform cortical (PC) neurons that project back to the OB. These will be tagged with channelrhodopsin-2 and identified by light sensitivity. Finally, we will express the spectrally distinct Ca++ indicators GCaMP6 and RCaMP2 in PC neurons and in olfactory sensory neurons, respectively, and use 2-photon microscopy to analyze the spatio-temporal relationship between feedforward and feedback inputs in the OB. This comprehensive approach will provide an explanation of how feedforward and feedback inputs are integrated to process complex stimuli.

1 500 000 €

Start date: 2018-04-01, End date: 2023-03-31

Our Universe appears to be filled with mysterious ingredients: 25 per cent appears to be dark matter, perhaps an as-yet undiscovered particle, and 70 per cent seems to be a bizarre fluid, dubbed dark energy, for which there is no satisfactory theory. Solving the dark energy problem is the most pressing question in cosmology today. It is possible that dark energy does not exist at all, and instead Einstein s theory of General Relativity is flawed. Cosmologists hope to measure the properties of the dark energy using the next generation of cosmological observations, in which I am playing a leading role. I believe the most promising technique to crack the dark energy problem is gravitational shear, in which images of distant galaxies are distorted as they pass through the intervening dark matter distribution. Analysis of the distortions allows a map of the dark matter to be reconstructed; by examining the dark matter distribution we uncover the nature of the apparent dark energy. However to capitalize on the great potential of gravitational shear we must measure incredibly small image distortions in the presence of much larger image modifications that occur in the measurement process. I am proposing a fresh look at this problem using an inter-disciplinary approach in collaboration with computer scientists. This grant would enable my team to play a central role in the key results from the upcoming Dark Energy Survey. We would further capitalize on the gravitational shear signal by moving away from the current dark energy bandwagon by instead focusing on testing General Relativity using novel approaches. Our work will produce results which will lead the next Einstein to solve the biggest puzzle in cosmology, and arguably physics.

1 400 000 €

Start date: 2010-04-01, End date: 2016-03-31