ERC FUNDED PROJECTS

This radically interdisciplinary project aims to bring a substantially new field of research – literature and mathematics studies – to prominence as a tool for investigating the culture of nineteenth-century Britain. It will result in three kinds of outcome: a monograph, two interdisciplinary and international colloquia, and a collection of essays. The project focuses on Euclidean geometry as a key element of nineteenth-century literary and scientific culture, showing that it was part of the shared knowledge flowing through elite and popular Romantic and Victorian writing, and figuring notably in the work of very many of the century’s best-known writers. Despite its traditional cultural prestige and educational centrality, geometry has been almost wholly neglected by literary history. This project shows how literature and mathematics studies can draw a new map of nineteenth-century British culture, revitalising our understanding of the Romantic and Victorian imagination through its writing about geometry.

323 118 €

Start date: 2009-01-01, End date: 2011-10-31

The traditional (Riemann) approach to analytic number theory uses the zeros of zeta functions. This requires the associated multiplicative function, say f(n), to have special enough properties that the associated Dirichlet series may be analytically continued. In this proposal we continue to develop an approach which requires less of the multiplicative function, linking the original question with the mean value of f. Such techniques have been around for a long time but have generally been regarded as “ad hoc”. In this project we aim to show that one can develop a coherent approach to the whole subject, not only reproving all of the old results, but also many new ones that appear inaccessible to traditional methods. Our first goal is to complete a monograph yielding a reworking of all the classical theory using these new methods and then to push forward in new directions. The most important is to extend these techniques to GL(n) L-functions, which we hope will now be feasible having found the correct framework in which to proceed. Since we rarely know how to analytically continue such L-functions this could be of great benefit to the subject. We are developing the large sieve so that it can be used for individual moduli, and will determine a strong form of that. Also a new method to give asymptotics for mean values, when they are not too small. We wish to incorporate techniques of analytic number theory into our theory, for example recent advances on mean values of Dirichlet polynomials. Also the recent breakthroughs on the sieve suggest strong links that need further exploration. Additive combinatorics yields important results in many areas. There are strong analogies between its results, and those for multiplicative functions, especially in large value spectrum theory, and its applications. We hope to develop these further. Much of this is joint work with K Soundararajan of Stanford University.

2 011 742 €

Start date: 2015-08-01, End date: 2020-07-31

A key synthetic challenge of widespread interest in chemical science involves the creation of well-defined 2D functional materials that exist on a length-scale of nanometers to microns. In this ambitious 5 year proposal we aim to tackle this issue by exploiting the unique opportunities made possible by recent developments with the living crystallization-driven self-assembly (CDSA) platform. Using this solution processing approach, amphiphilic block copolymers (BCPs) with crystallizable blocks, related amphiphiles, and polymers with charged end groups will be used to predictably construct monodisperse samples of tailored, functional soft matter-based 2D nanostructures with controlled shape, size, and spatially-defined chemistries. Many of the resulting nanostructures will also offer unprecedented opportunities as precursors to materials with hierarchical structures through further solution-based “bottom-up” assembly methods. In addition to fundamental studies, the proposed work also aims to make important impact in the cutting-edge fields of liquid crystals, interface stabilization, catalysis, supramolecular polymers, and hierarchical materials.

2 499 597 €

Start date: 2018-05-01, End date: 2023-04-30

Quantum optics, the study of how discrete packets of light (photons) and matter interact, has led to the development of remarkable new technologies which exploit the bizarre properties of quantum mechanics. These quantum technologies are primed to revolutionize the fields of communication, information processing, and metrology in the coming years. Similar to contemporary technologies, the future quantum machinery will likely consist of a semiconductor platform to create and process the quantum information. However, to date the demanding requirements on a quantum photonic platform have yet to be satisfied with conventional bulk (three-dimensional) semiconductors. To surmount these well-known obstacles, a new paradigm in quantum photonics is required. Initiated by the recent discovery of single photon emitters in atomically flat (two-dimensional) semiconducting materials, 2DQP aims to be at the nucleus of a new approach by realizing quantum optics with ultra-stable (coherent) quantum states integrated into devices with electronic and photonic functionality. We will characterize, identify, engineer, and coherently manipulate localized quantum states in this two-dimensional quantum photonic platform. A vital component of 2DQP’s vision is to go beyond the fundamental science and achieve the ideal solid-state single photon device yielding perfect extraction - 100% efficiency - of on-demand indistinguishable single photons. Finally, we will exploit this ideal device to implement the critical building block for a photonic quantum computer.

1 999 135 €

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

This proposal relates to the Proof of Concept stage investigation of exciting new findings in the ERC Advanced Grant ‘IMPUNEP’ project relating to the study and use of plasma-based processes. These findings offer significant advantages for the creation of complex 3D ceramic and ceramic-metal products at relatively low cost in an environmentally friendly manner. The potential applications of this new technology are very wide-ranging, and include the creation of new products as diverse as healthcare devices, MEMS and aero/automotive parts. Before we properly and fully identify the most promising applications, we need to investigate key aspects of the performance of materials created by this new method. This aspect wasn’t envisaged in the original proposal and involves research into the mechanical properties (especially the strength and elastic modulus) of these 3D parts and their response to deformation and dynamic displacements, as well as their physical (including electrical) properties. These components will be highly resistant to attack by aggressive (e.g. acidic) media as well as highly tolerant to both low (cryogenic) and high (combustion) temperatures. The expected applications opened up by this new method to produce ceramic and ceramic-metal components of complex shape are extensive. Hence the need for this Proof of Concept study, which will focus on validating the process for 3D ceramic-metal and ceramic parts and evaluating the mechanical, chemical, electrical and physical attributes of the 3D shapes, and will explore their potential applications in this pre-demonstration phase.

149 500 €

Start date: 2019-01-01, End date: 2020-03-31

Polar materials, such as piezoelectrics and ferroelectrics are essential to our modern life, yet they are mostly developed by trial-and-error. Their properties overwhelmingly depend on the defects within them, the majority of which are hidden in the bulk. The road to better materials is via mapping these defects, but our best tool for it – piezoresponse force microscopy (PFM) – is limited to surfaces. 3D-PXM aims to revolutionize our understanding by measuring the local structure-property correlations around individual defects buried deep in the bulk. This is a completely new kind of microscopy enabling 3D maps of local strain and polarization (i.e. piezoresponse) with 10 nm resolution in mm-sized samples. It is novel, multi-scale and fast enough to capture defect dynamics in real time. Uniquely, it is a full-field method that uses a synthetic-aperture approach to improve both resolution and recover the image phase. This phase is then quantitatively correlated to local polarization and strain via a forward model. 3D-PXM combines advances in X-Ray optics, phase recovery and data analysis to create something transformative. In principle, it can achieve spatial resolution comparable to the best coherent X-Ray microscopy methods while being faster, used on larger samples, and without risk of radiation damage. For the first time, this opens the door to solving how defects influence bulk properties under real-life conditions. 3D-PXM focuses on three types of defects prevalent in polar materials: grain boundaries, dislocations and polar nanoregions. Individually they address major gaps in the state-of-the-art, while together making great strides towards fully understanding defects. This understanding is expected to inform a new generation of multi-scale models that can account for a material’s full heterogeneity. These models are the first step towards abandoning our tradition of trial-and-error, and with this comes the potential for a new era of polar materials.

1 496 941 €

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

"Understanding structure-property relationships across lengthscales is key to the design of functional and structural materials and devices. Moreover, the complexity of modern devices extends to three dimensions and as such 3D characterization is required across those lengthscales to provide a complete understanding and enable improvement in the material’s physical and chemical behaviour. 3D imaging and analysis from the atomic scale through to granular microstructure is proposed through the development of electron tomography using (S)TEM, and ‘dual beam’ SEM-FIB, techniques offering complementary approaches to 3D imaging across lengthscales stretching over 5 orders of magnitude. We propose to extend tomography to include novel methods to determine atom positions in 3D with approaches incorporating new reconstruction algorithms, image processing and complementary nano-diffraction techniques. At the nanoscale, true 3D nano-metrology of morphology and composition is a key objective of the project, minimizing reconstruction and visualization artefacts. Mapping strain and optical properties in 3D are ambitious and exciting challenges that will yield new information at the nanoscale. Using the SEM-FIB, 3D ‘mesoscale’ structures will be revealed: morphology, crystallography and composition can be mapped simultaneously, with ~5nm resolution and over volumes too large to tackle by (S)TEM and too small for most x-ray techniques. In parallel, we will apply 3D imaging to a wide variety of key materials including heterogeneous catalysts, aerospace alloys, biomaterials, photovoltaic materials, and novel semiconductors. We will collaborate with many departments in Cambridge and institutes worldwide. The personnel on the proposal will cover all aspects of the tomography proposed using high-end TEMs, including an aberration-corrected Titan, and a Helios dual beam. Importantly, a postdoc is dedicated to developing new algorithms for reconstruction, image and spectral processing."

2 337 330 €

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

Understanding how the brain processes information is one of the unsolved grand challenges in science. Moreover, neurological disorders, which disrupt information processing, have an enormous societal and economic impact. Studying information processing in the brain requires measurements of signals as they flow through neural circuits. However, the 3D nature of brain circuits and the speed of information transfer makes it difficult for neuroscientists to measure their properties with sufficiently high spatial and temporal resolution. During the NEUROGAIN ERC project, we developed a novel type of Acousto-Optic Lens (AOL)-based high-speed 3D laser scanner. This technology enables the focusing and scanning of a laser beam at 20-40 kHz. This scanning technology can be added to existing two-photon microscopes to enable 3D imaging of neurons and circuits with unprecedented spatio-temporal resolution. Moreover, it also automatically corrects for brain movement in real-time providing sharper images. This ERC PoC will facilitate commercialization of this 3D scanning technology by providing support to explore the markets in biosciences and beyond, protect the IP and facilitate early stage manufacture and assembly of AOL 3D scanners to supply biomedical researchers.

150 000 €

Start date: 2019-06-01, End date: 2020-11-30

This project presents a new concept for the detection, diagnosis and monitoring of cancer biomarker patterns in point-of-care. The device under development will make use of the selectivity of the plastic antibodies as sensing materials and the interference they will play on the normal operation of a photovoltaic cell. Plastic antibodies will be designed by surface imprinting procedures. Self-assembled monolayer and molecular imprinting techniques will be merged in this process because they allow the self-assembly of nanostructured materials on a “bottom-up” nanofabrication approach. A dye-sensitized solar cell will be used as photovoltaic cell. It includes a liquid interface in the cell circuit, which allows the introduction of the sample (also in liquid phase) without disturbing the normal cell operation. Furthermore, it works well with rather low cost materials and requires mild and easy processing conditions. The cell will be equipped with plasmonic structures to enhance light absorption and cell efficiency. The device under development will be easily operated by any clinician or patient. It will require ambient light and a regular multimeter. Eye detection will be also tried out.

998 584 €

Start date: 2013-02-01, End date: 2018-01-31

Spintronics, in which both the spin and the charge of the electron are used, is one of the most exciting new disciplines to emerge from nanoscience. The 3SPIN project seeks to open a new research front within spintronics: namely 3-dimensional spintronics, in which magnetic nanostructures are formed into a 3-dimensional interacting network of unrivalled density and hence technological benefit. 3SPIN will explore early-stage science that could underpin 3-dimensional metallic spintronics. The thesis of the project is: that by careful control of the constituent nanostructure properties, a 3-dimensional medium can be created in which a large number of topological solitons can exist. Although hardly studied at all to date, these solitons should be stable at room temperature, extremely compact and easy to manipulate and propagate. This makes them potentially ideal candidates to form the basis of a new spintronics in which the soliton is the basic transport vector instead of electrical current. ¬3.5M of funding is requested to form a new team of 5 researchers who, over a period of 60 months, will perform computer simulations and experimental studies of solitons in 3-dimensional networks of magnetic nanostructures and develop a laboratory demonstrator 3-dimensional memory device using solitons to represent and store data. A high performance electron beam lithography system (cost 1M¬) will be purchased to allow state-of-the-art magnetic nanostructures to be fabricated with perfect control over their magnetic properties, thus allowing the ideal conditions for solitons to be created and controllably manipulated. Outputs from the project will be a complete understanding of the properties of these new objects and a road map charting the next steps for research in the field.

2 799 996 €

Start date: 2010-03-01, End date: 2016-02-29

Serotonin (5-HT) is implicated in a wide spectrum of brain functions and disorders. However, its functions remain controversial and enigmatic. We suggest that past work on the 5-HT system have been significantly hampered by technical limitations in the selectivity and temporal resolution of the conventional pharmacological and electrophysiological methods that have been applied. We therefore propose to apply novel optogenetic methods that will allow us to overcome these limitations and thereby gain new insight into the biological functions of this important molecule. In preliminary studies, we have demonstrated that we can deliver exogenous proteins specifically to 5-HT neurons using viral vectors. Our objectives are to (1) record, (2) stimulate and (3) silence the activity of 5-HT neurons with high molecular selectivity and temporal precision by using genetically-encoded sensors, activators and inhibitors of neural function. These tools will allow us to monitor and control the 5-HT system in real-time in freely-behaving animals and thereby to establish causal links between information processing in 5-HT neurons and specific behaviors. In combination with quantitative behavioral assays, we will use this approach to define the role of 5-HT in sensory, motor and cognitive functions. The significance of the work is three-fold. First, we will establish a new arsenal of tools for probing the physiological and behavioral functions of 5-HT neurons. Second, we will make definitive tests of major hypotheses of 5-HT function. Third, we will have possible therapeutic applications. In this way, the proposed work has the potential for a major impact in research on the role of 5-HT in brain function and dysfunction.

2 318 636 €

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

When faced with a threat, an animal must decide whether to freeze, reducing its chances of being noticed, or to flee to the safety of a refuge. Animals from fish to primates choose between these two alternatives when confronted by an attacking predator, a choice that largely depends on the context in which the threat occurs. Recent work has made strides identifying the pre-motor circuits, and their inputs, which control freezing behavior in rodents, but how contextual information is integrated to guide this choice is still far from understood. We recently found that fruit flies in response to visual looming stimuli, simulating a large object on collision course, make rapid freeze/flee choices that depend on the social and spatial environment, and the fly’s internal state. Further, identification of looming detector neurons was recently reported and we identified the descending command neurons, DNp09, responsible for freezing in the fly. Knowing the sensory input and descending output for looming-evoked freezing, two environmental factors that modulate its expression, and using a genetically tractable system affording the use of large sample sizes, places us in an unique position to understand how a information about a threat is integrated with cues from the environment to guide the choice of whether to freeze (our goal). To assess how social information impinges on the circuit for freezing, we will examine the sensory inputs and neuromodulators that mediate this process, mapping their connections to DNp09 neurons (Aim 1). We ask whether learning is required for the spatial modulation of freezing, which cues flies are using to discriminate different places and which brain circuits mediate this process (Aim 2). Finally, we will study how activity of DNp09 neurons drives freezing (Aim 3). This project will provide a comprehensive understanding of the mechanism of freezing and its modulation by the environment, from single neurons to behaviour.

1 969 750 €

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

"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

"Recently through de novo peptide design, we have discovered and presented a new protein structure. This is an all-parallel, 6-helix bundle with a continuous central channel of 0.5 – 0.6 nm diameter. We posit that this is one of a broader class of protein structures that we call the alpha-helical barrels. Here, in three Work Packages, we propose to explore these structures and to develop protein functions within them. First, through a combination of computer-aided design, peptide synthesis and thorough biophysical characterization, we will examine the extents and limits of the alpha-helical-barrel structures. Whilst this is curiosity driven research, it also has practical consequences for the studies that will follow; that is, alpha-helical barrels made from increasing numbers of helices have channels or pores that increase in a predictable way. Second, we will use rational and empirical design approaches to engineer a range of functions within these cavities, including binding capabilities and enzyme-like activities. Finally, and taking the programme into another ambitious area, we will use the alpha-helical barrels to template other folds that are otherwise difficult to design and engineer, notably beta-barrels that insert into membranes to render ion-channel and sensor functions."

2 467 844 €

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

Multidrug resistance of pathogenic bacteria has become a serious threat to public health. The need to develop novel technologies to combat the evolution of bacterial drug resistance is clearly a matter of public concern and urgency. The consequences of AMR include (i) reducing our ability to treat common infectious, resulting in prolonged illness and a greater risk of complications; (ii) patients remaining infectious for longer due to ineffective treatments, making them more likely to pass infections on to others; (iii) compromising advances in modern medicine (such as organ transplantation or chemotherapy) due to risk of infection; and (iv) increasing economic burden on health care systems, families, and societies. This project aims to assess the commercial viability of an alternative approach to this problem.

150 000 €

Start date: 2019-08-01, End date: 2021-01-31

What is the origin of cosmic rays, what are the dominant acceleration mechanisms in relativistic shocks, how do cosmic rays self-consistently influence the shock dynamics, how are relativistic collisionless shocks formed are longstanding scientific questions, closely tied to extreme plasma physics processes, and where a close interplay between the micro-instabilities and the global dynamics is critical. Relativistic shocks are closely connected with the propagation of intense streams of particles pervasive in many astrophysical scenarios. The possibility of exciting shocks in the laboratory will also be available very soon with multi-PW lasers or intense relativistic particle beams. Computational modeling is now established as a prominent research tool, by enabling the fully kinetic modeling of these systems for the first time. With the fast paced developments in high performance computing, the time is ripe for a focused research programme on simulation-based studies of relativistic shocks. This proposal therefore focuses on using self-consistent ab initio massively parallel simulations to study the physics of relativistic shocks, bridging the gap between the multidimensional microphysics of shock onset, formation, and propagation and the global system dynamics. Particular focus will be given to the shock acceleration mechanisms and the radiation signatures of the various physical processes, with the goal of solving some of the central questions in plasma/relativistic phenomena in astrophysics and in the laboratory, and opening new avenues between theoretical/massive computational studies, laboratory experiments and astrophysical observations.

1 588 800 €

Start date: 2011-06-01, End date: 2016-07-31

Clouds play a key role in the climate system. Small anthropogenic perturbations of the cloud system potentially have large radiative effects. Aerosols perturb the global radiation budget directly, by scattering and absorption, as well as indirectly, by the modification of cloud properties and occurrence. The applicability of traditional conceptual models of indirect aerosol effects to convective clouds is disputed as cloud dynamics complicates the picture. Strong evidence for numerous aerosol effects on convection has been established in individual disciplines: through remote sensing and in-situ observations as well as by cloud resolving and global modelling. However, a coherent scientific view of the effects of aerosols on convection has yet to be established. The primary objective of ACCLAIM is to recast the effects of aerosols on convective clouds as basis for improved global estimates of anthropogenic climate effects. Specific objectives include: i) to unravel the governing principles of aerosol effects on convective clouds; ii) provide quantitative constraints on satellite-retrieved relationships between convective clouds and aerosols; and ultimately iii) to enable global climate models to represent the full range of anthropogenic climate perturbations and quantify the climate response to aerosol effects on convective clouds. I have developed the research strategy of ACCLAIM to overcome disciplinary barriers in this frontier research area and seek five years of funding to establish an interdisciplinary, physics focused, research group consisting of two PostDocs, two PhD students and myself. ACCLAIM will be centred around global aerosol-convection climate modelling studies, complemented by research constraining aerosol-convection interactions through remote sensing and a process focused research strand, advancing fundamental understanding and global model parameterisations through high resolution aerosol-cloud modelling in synergy with in-situ observations.

1 429 243 €

Start date: 2011-09-01, End date: 2017-02-28

Increasing crop yield to feed the world is a grand challenge of the 21st century but it is hampered by diseases caused by filamentous plant pathogens. The arms race between pathogen and plant demands constant adjustment of crop germplasm to tackle emerging pathogen races with new virulence features. To date, most crop disease resistance has relied on specific resistance genes that are effective only against a subset of races. We cannot solely rely on classical resistance genes to keep ahead of the pathogens. There is an urgent need to develop approaches based on knowledge of the pathogen’s Achilles heel: core plant processes that are required for pathogen colonization. Our hypothesis is that disease resistance based on manipulation of host accessibility processes has a higher probability for durability, and is best identified using a broad host-range pathogen. I will employ the filamentous pathogen Phytophthora palmivora to mine plant alleles and unravel host processes providing microbial access in roots and leaves of monocot and dicot plants. In Aim 1 I will utilize plant symbiosis mutants and allelic variation to elucidate general mechanisms of colonization by filamentous microbes. Importantly, allelic variation will be studied in economically relevant barley and wheat to allow immediate translation into breeding programs. In Aim 2 I will perform a comparative study of microbial colonization in monocot and dicot roots and leaves. Transcriptional profiling of pathogen and plant will highlight common and contrasting principles and illustrate the impact of differential plant anatomies. We will challenge our findings by testing beneficial fungi to assess commonalities and differences between mutualist and pathogen colonization. We will use genetics, cell biology and genomics to find suitable resistance alleles highly relevant to crop production and global food security. At the completion of the project, I expect to have a set of genes for resistance breeding.

1 991 054 €

Start date: 2015-09-01, End date: 2021-08-31

"Combustion is essential to the world’s energy generation and transport needs, and will remain so for the foreseeable future. Mitigating its impact on the climate and human health, by reducing its associated emissions, is thus a priority. One significant challenge for gas-turbine combustion is combustion instability, which is currently inhibiting reductions in NOx emissions (these damage human health via a deterioration in air quality). Combustion instability is caused by a two-way coupling between unsteady combustion and acoustic waves - the large pressure oscillations that result can cause substantial mechanical damage. Currently, the lack of fast, accurate modelling tools for combustion instability, and the lack of reliable ways of suppressing it are severely hindering reductions in NOx emissions. This proposal aims to make step improvements in both fast, accurate modelling of combustion instability, and in developing reliable active control strategies for its suppression. It will achieve this by coupling low order combustor models (these are fast, simplified models for simulating combustion instability) with advances in analytical modelling, CFD simulation, reduced order modelling and control theory tools. In particular: * important advances in accurately incorporating the effect of entropy waves (temperature variations resulting from unsteady combustion) and non-linear flame models will be made; * new active control strategies for achieving reliable suppression of combustion instability, including from within limit cycle oscillations, will be developed; * an open-source low order combustor modelling tool will be developed and widely disseminated, opening access to researchers worldwide and improving communications between the fields of thermoacoustics and control theory. Thus the proposal aims to use analytical and computational methods to contribute to achieving low NOx gas-turbine combustion, without the penalty of damaging combustion instability."

1 489 309 €

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

Computer models based on known physical laws are our primary tool for predicting climate change. Yet the state-of-the-art models exhibit a disturbingly wide range of predictions of future climate change, especially when examined at the regional scale, which has not decreased as the models have become more comprehensive. The reasons for this are not understood. This represents a basic challenge to our fundamental understanding of climate. The divergence of model projections is presumably related to systematic model errors in the large-scale fluxes of heat, moisture and momentum that control regional aspects of climate. That these errors stubbornly persist in spite of increases in the spatial resolution of the models suggests that they are associated with errors in the representation of unresolved processes, whose effects must be parameterised. Most attention in climate science has hitherto focused on the thermodynamic aspects of climate. Dynamical aspects, which involve the atmospheric circulation, have received much less attention. However regional climate, including persistent climate regimes and extremes, is strongly controlled by atmospheric circulation patterns, which exhibit chaotic variability and whose representation in climate models depends sensitively on parameterised processes. Moreover the dynamical aspects of model projections are much less robust than the thermodynamic ones. There are good reasons to believe that model bias, the divergence of model projections, and chaotic variability are somehow related, although the relationships are not well understood. This calls for studying them together. My proposed research will focus on this problem, addressing these three aspects of the atmospheric circulation response to climate change in parallel: (i) diagnosing the sources of model error; (ii) elucidating the relationship between model error and the spread in model projections; (iii) understanding the physical mechanisms of atmospheric variability.

2 489 151 €

Start date: 2014-03-01, End date: 2020-02-29

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

MAL: an actin-regulated SRF transcriptional coactivator Recent years have seen a revitalised interest in the role of actin in nuclear processes, but the molecular mechanisms involved remain largely unexplored. We will elucidate the molecular basis for the actin-based control of the SRF transcriptional coactivator, MAL. SRF controls transcription through two families of coactivators, the actin-binding MRTFs (MAL, Mkl2), which couple its activity to cytoskeletal dynamics, and the ERK-regulated TCFs (Elk-1, SAP-1, Net). MAL subcellular localisation and transcriptional activity responds to signal-induced changes in G-actin concentration, which are sensed by its actin-binding N-terminal RPEL domain. Members of a second family of RPEL proteins, the Phactrs, also exhibit actin-regulated nucleocytoplasmic shuttling. The proposal addresses the following novel features of actin biology: ¿ Actin as a transcriptional regulator ¿ Actin as a signalling molecule ¿ Actin-binding proteins as targets for regulation by actin, rather than regulators of actin function We will analyse the sequences and proteins involved in actin-regulated nucleocytoplasmic shuttling, using structural biology and biochemistry to analyse its control by changes in actin-RPEL domain interactions. We will characterise the dynamics of shuttling, and develop reporters for changes in actin-MAL interaction for analysis of pathway activation in vivo. We will identify genes controlling MAL itself, and the balance between the nuclear and cytoplasmic actin pools. The mechanism by which actin represses transcriptional activation by MAL in the nucleus, and its relation to MAL phosphorylation, will be elucidated. Finally, we will map MRTF and TCF cofactor recruitment to SRF targets on a genome-wide scale, and identify the steps in transcription controlled by actin-MAL interaction.

1 889 995 €

Start date: 2011-10-01, End date: 2017-09-30

The brain evolves, develops, and operates in the context of animal movements. As a consequence, fundamental brain functions such as spatial perception and motor control critically depend on the precise knowledge of the ongoing body motion. An accurate internal estimate of self-movement is thought to emerge from sensorimotor integration; nonetheless, which circuits perform this internal estimation, and exactly how motor-sensory coordination is implemented within these circuits are basic questions that remain to be poorly understood. There is growing evidence suggesting that, during locomotion, motor-related and visual signals interact at early stages of visual processing. In mammals, however, it is not clear what the function of this interaction is. Recently, we have shown that a population of Drosophila optic-flow processing neurons —neurons that are sensitive to self-generated visual flow, receives convergent visual and walking-related signals to form a faithful representation of the fly’s walking movements. Leveraging from these results, and combining quantitative analysis of behavior with physiology, optogenetics, and modelling, we propose to investigate circuit mechanisms of self-movement estimation during walking. We will:1) use cell specific manipulations to identify what cells are necessary to generate the motor-related activity in the population of visual neurons, 2) record from the identified neurons and correlate their activity with specific locomotor parameters, and 3) perturb the activity of different cell-types within the identified circuits to test their role in the dynamics of the visual neurons, and on the fly’s walking behavior. These experiments will establish unprecedented causal relationships among neural activity, the formation of an internal representation, and locomotor control. The identified sensorimotor principles will establish a framework that can be tested in other scenarios or animal systems with implications both in health and disease.

1 500 000 €

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

The mechanism of cell division is conserved in many eukaryotes, from yeast to man. A contractile ring of filamentous actin and myosin II motors generates the force to bisect a mother cell into two daughters. The actomyosin ring is among the most complex cellular machines, comprising over 150 proteins. Understanding how these proteins organize themselves into a functional ring with appropriate contractile properties remains one of the great challenges in cell biology. Efforts to generate a comprehensive understanding of the mechanism of actomyosin ring assembly have been hampered by the lack of structural information on the arrangement of actin, myosin II, and actin modulators in the ring in its native state. Fundamental questions such as how actin filaments are assembled and organized into a ring remain actively debated. This project will investigate key issues pertaining to cytokinesis in the fission yeast Schizosaccharomyces pombe, which divides employing an actomyosin based contractile ring, using the methods of genetics, biochemistry, cellular imaging, DNA origami, genetic code expansion, and click chemistry. Specifically, we will (1) attempt to visualize actin filament assembly in live cells expressing fluorescent actin generated through synthetic biological approaches, including genetic code expansion and click chemistry (2) decipher actin filament polarity in the actomyosin ring using total internal reflection fluorescence microscopy of labelled dimeric and multimeric myosins V and VI generated through DNA origami approaches (3) address when, where, and how actin filaments for cytokinesis are assembled and organized into a ring and (4) reconstitute actin filament and functional actomyosin ring assembly in permeabilized spheroplasts and in supported bilayers. Success in the project will provide major insight into the mechanism of actomyosin ring assembly and illuminate principles behind cytoskeletal self-organization.

2 863 705 €

Start date: 2015-11-01, End date: 2020-10-31