ERC FUNDED PROJECTS

The aim of the present proposal is to establish a research team developing and exploiting innovative techniques to study conformal field theories (CFT) analytically. Our approach does not rely on a Lagrangian description but on symmetries and consistency conditions. As such it applies to any CFT, offering a unified framework to study generic CFTs analytically. The initial implementation of this program has already led to striking new results and insights for both Lagrangian and non-Lagrangian CFTs. The overarching aims of my team will be: To develop an analytic bootstrap program for CFTs in general dimensions; to complement these techniques with more traditional methods and develop a systematic machinery to obtain analytic results for generic CFTs; and to use these results to gain new insights into the mathematical structure of the space of quantum field theories. The proposal will bring together researchers from different areas. The objectives in brief are: 1) Develop an alternative to Feynman diagram computations for Lagrangian CFTs. 2) Develop a machinery to compute loops for QFT on AdS, with and without gravity. 3) Develop an analytic approach to non-perturbative N=4 SYM and other CFTs. 4) Determine the space of all CFTs. 5) Gain new insights into the mathematical structure of the space of quantum field theories. The outputs of this proposal will include a new way of doing perturbative computations based on symmetries; a constructive derivation of the AdS/CFT duality; new analytic techniques to attack strongly coupled systems and invaluable new lessons about the space of CFTs and QFTs. Success in this research will lead to a completely new, unified way to view and solve CFTs, with a huge impact on several branches of physics and mathematics.

2 171 483 €

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

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

Gas turbines are an essential ingredient in the long-term energy and aviation mix. They are flexible, offer fast start-up and the ability to burn renewable-generated fuels. However, they generate NOx emissions, which cause air pollution and damage human health, and reducing these is an air quality imperative. A major hurdle to this is that lean premixed combustion, essential for further NOx emission reductions, is highly susceptible to thermoacoustic instability. This is caused by a two-way coupling between unsteady combustion and acoustic waves, and the resulting large pressure oscillations can cause severe mechanical damage. Computational methods for predicting thermoacoustic instability, fast and accurate enough to be used as part of the industrial design process, are urgently needed. The only computational methods with the prospect of being fast enough are those based on coupled treatment of the acoustic waves and unsteady combustion. These exploit the amenity of the acoustic waves to analytical modelling, allowing costly simulations to be directed only at the more complex flame. They show real promise: my group recently demonstrated the first accurate coupled predictions for lab-scale combustors. The method does not yet extend to industrial combustors, the more complex flow-fields in these rendering current acoustic models overly-simplistic. I propose to comprehensively overhaul acoustic models across the entirety of the combustor, accounting for real and important acoustic-flow interactions. These new models will offer the breakthrough prospect of extending efficient, accurate predictive capability to industrial combustors, which has a real chance of facilitating future, instability free, very low NOx gas turbines.

1 985 288 €

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

Over the past 2 years we have developed and patented a new actuator which is based on composite polymer/metal nanoparticles. Originally designed to create strong reversible colour changes, we found that the forces generated in the actuation exceed current microscale devices by nearly two orders of magnitude (weight for weight). We have thus protected and developed this possibility using my Advanced ERC project, LINASS, together with Cambridge Enterprise (CE, the commercialisation arm of the University of Cambridge). We have now reached the stage where we believe that this can become commercially interesting, have progressed to a better understanding of the fundamental processes, and have some idea of the applications that it might enable. The PoC project here is thus conceived to create demonstrators in two related domains: one offers new possibilities in advancing the established technology of microfluidic chips, while the other opens up a new space entirely, by making DNA nano-machines active and feasibly exploitable.

144 549 €

Start date: 2018-01-01, End date: 2019-06-30

The project will develop a new ethnography of statehood through architecture. It goes beyond conventional approaches to statehood, which describe states as an objectively existing set of tools used to run a country, and critical approaches that understand them as discursive constructs. Instead, this research understands statehood as a result of the relationship between functions and symbols, and will read it through an innovative new methodology, namely a study of state architecture. The study will focus on state buildings in Africa. African statehood, uncertain and often ambiguous, in many cases profoundly shaped by colonial heritages and post-colonial relationships, is reflected in classical-colonial, modernist-nationalist and post-modern or vernacular styles of architecture. African state buildings reveal the complex interplay of ideas, activities and relationships that together constitute an often uncomfortable statehood. They symbolise the state, embodying and projecting ideas of it through their aesthetics; they enable its concrete functions and processes; and they reveal what citizens think about the state in the ways they describe and negotiate them. The study is comparative, multi-layered and interdisciplinary. It focuses on seven countries (South Africa, Tanzania, DR Congo, Ethiopia, Ghana, Côte d’Ivoire and Guinea Bissau), exploring politics and statehood on domestic, regional and international levels, and drawing on theory and methods from political science, history, sociology, art and architecture theory. It employs innovative ethnographic methods, including the collection and display of photographs in interactive exhibitions staged in Africa to explore the ways citizens think about and use state buildings. This project will provide an innovative reading of how African statehood is expressed and how it looks and feels to African citizens. In doing this, it will make a distinctive new contribution to understanding how statehood works everywhere.

1 870 665 €

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

Autophagy is a conserved, lysosomal-mediated pathway required for cell homeostasis and survival. It is controlled by the master regulators of energy (AMPK) and growth (TORC1) and mediated by the ATG (autophagy) proteins. Deregulation of autophagy is implicated in cancer, immunity, infection, aging and neurodegeneration. Autophagosomes form and expand using membranes from the secretory and endocytic pathways but how this occurs is not understood. ATG9, the only transmembrane ATG protein traffics through the cell in vesicles, and is essential for rapid initiation and expansion of the membranes which form the autophagosome. Crucially, how ATG9 functions is unknown. I will determine how ATG9 initiates the formation and expansion of the autophagosome by amino acid starvation through a molecular dissection of proteins resident in ATG9 vesicles which modulate the composition and property of the initiating membrane. I will employ high resolution light and electron microscopy to characterize the nucleation of the autophagosome, proximity-specific biotinylation and quantitative Mass Spectrometry to uncover the proteome required for the function of the ATG9, and optogenetic tools to acutely regulate signaling lipids. Lastly, with our tools and knowledge I will develop an in vitro reconstitution system to define at a molecular level how ATG9 vesicle proteins, membranes that interact with ATG9 vesicles, and other accessory ATG components nucleate and form an autophagosome. In vitro reconstitution of autophagosomes will be assayed biochemically, and by correlative light and cryo-EM and cryo-EM tomography, while functional reconstitution of autophagy will be tested by selective cargo recruitment. The development of a reconstituted system and identification proteins and lipids which are key components for autophagosome formation will provide a means to identify a new generation of targets for translational work leading to manipulation of autophagy for disease related therapies.

2 121 055 €

Start date: 2018-07-01, End date: 2023-06-30

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

1 725 982 €

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

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

1 999 755 €

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

Imagine in the future, bionic devices that can merge device and biology which can perform molecular sensing, simulate the functions of grown-organs in the lab, or even replace or improve parts of the organ as smart implants? Such bionic devices is set to transform a number of emerging fields, including synthetic biotechnology, regenerative medicine, and human-machine interfaces. Merging biology and man-made devices also mean that materials of vastly different properties need to be seamlessly integrated. One of the promising strategies to manufacture these devices is through 3D printing, which can structure different materials into functional devices, and simultaneously intertwining with biological matters. However, the requirement for biocompatibility, miniaturisation, portability and high performance in bionic devices pushes the current limit for micro- nanoscale 3D printing. This proposal aims to develop a new multi-material, cross-length scale biofabrication platform, with specific focus in making future smart bionic devices. In particular, a new mechanism is proposed to smoothly interface diverse classes of materials, such that an active device component can be ‘shrunk’ into a single small fibre. This mechanism utilises the polymeric materials’ flow property under applied tensile forces, and their abilities to combine with other classes of materials, such as semi-conductors and metals to impart further functionalities. This smart device fibre can be custom-made to perform different tasks, such as light emission or energy harvesting, to bridge 3D bioprinting for the future creation of high performance, compact, and cell-friendly bionic and medical devices.

1 486 938 €

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

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

149 901 €

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

Social media platforms have become tools for manipulating public opinion during elections. In particular, “bots” are algorithms that automate rapid, widespread interactions with citizens, often with deleterious effects on public knowledge of science, social inequality, and public policy options. Through the ERC COMPROP Consolidator award, researchers have demonstrated that even simple bots (i) effectively keep negative messages and fake news in circulation longer (ii) target journalists and civil society groups and (iii) operate with little oversight from social media firms. Such algorithms have negative consequences both for public trust in technology innovation and for the quality of public deliberation in Europe’s democracies. ERC researchers have been able to identify highly automated, politically-manipulative social media accounts post hoc. This project will allow researchers to take what we have learned and produce an online tool that allows people to evaluate suspicious social media accounts. Most social media platforms are slow to address troll and bot activity, so this innovative tool will put ERC research into public service in Europe—and around the world.

149 921 €

Start date: 2017-08-01, End date: 2019-01-31

Person-centred care is a core health value of modern health care. The overarching aim of C-POS (Children's Palliative care Outcome Scale) is to develop and validate a person-centred outcome measure for children, young people (CYP) and their families affected by life-limiting & life-threatening conditions (LLLTC). International systematic reviews, and clinical guides have highlighted that currently none exists. This novel study will draw together a unique multidisciplinary collaboration to pioneer new methods, enabling engagement in outcome measurement by a population currently neglected in research. C-POS builds on an international program of work. The sequential mixed methods will collect substantive data through objectives to determine i) the primary concerns of CYP and their families affected by LLLTC & preferences to enable participation in ethical person-centred measurement (n=50); ii) view of clinicians and commissioners on optimal implementation methods (national Delphi study); iii) a systematic review of current data collection tools for CYP regardless of condition; iv) integration of objectives i-iii to develop a tool (C-POS) with face and content validity; v) cognitive interviews to determine interpretability (n=40); vi) longitudinal cohort of CYP and families to determine test-retest reliability, internal consistency, construct validity and responsiveness (n=151); vii) development of resources for routine implementation viii) translation and interpretation protocols for international adoption. C-POS is an ambitious study that, for the first time, will enable measurement of person-centred outcomes of care. This will be a turning point in the scientific study of a hitherto neglected group.

1 799 820 €

Start date: 2018-09-01, End date: 2023-02-28

According to string theory, coherent sheaves on three-dimensional Calabi-Yau spaces encode fundamental properties of the universe. On the other hand, they have a purely mathematical definition. We will develop and use the new field of categorified Donaldson-Thomas (DT) theory, which counts these objects. Via the powerful perspective of noncommutative algebraic geometry, this theory has found application in recent years in a wide variety of contexts, far from classical algebraic geometry. Categorification has proved tremendously powerful across mathematics, for example the entire subject of algebraic topology was started by the categorification of Betti numbers. The categorification of DT theory leads to the replacement of the numbers of DT theory by vector spaces, of which these numbers are the dimensions. In the area of categorified DT theory we have been able to prove fundamental conjectures upgrading the famous wall crossing formula and integrality conjecture in noncommutative algebraic geometry. The first three projects involve applications of the resulting new subject: 1. Complete the categorification of quantum cluster algebras, proving the strong positivity conjecture. 2. Use cohomological DT theory to prove the outstanding conjectures in the nonabelian Hodge theory of Riemann surfaces, and the subject of Higgs bundles. 3. Prove the comparison conjecture, realising the study of Yangian quantum groups and the geometric representation theory around them as a special case of DT theory. The final objective involves coming full circle, and applying our recent advances in noncommutative DT theory to the original theory that united string theory with algebraic geometry: 4. Develop a generalised theory of categorified DT theory extending our results in noncommutative DT theory, proving the integrality conjecture for categories of coherent sheaves on Calabi-Yau 3-folds.

1 239 435 €

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

The way in which normative principles (“norms”) matter in world politics is now a key area of international relations research. Yet we have limited understanding of why some norms emerge and gain traction globally whereas others do not. The politics of loss and damage related to climate change offers a paradigm case for studying the emergence of - and contestation over - norms, specifically justice norms. The parties to the UN Framework Convention on Climate Change (UNFCCC) have recently acknowledged that there is an urgent need to address the inevitable, irreversible consequences of climate change. Yet within this highly contested policy area - which includes work on disaster risk reduction; non-economic losses (e.g. loss of sovereignty); finance and climate-related migration - there is little consensus about what loss and damage policy means or what it requires of the global community, of states and of the (current and future) victims of climate change. Relying on an interdisciplinary theoretical approach and an ethnographic methodology that traverses scales of governance, my project - The Politics of Climate Change Loss and Damage (CCLAD) - will elucidate the conditions under which a norm is likely to become hegemonic, influential, contested or reversed by introducing a new understanding of the fluid nature of norm-content. I argue that norms are partly constituted through the practices of policy-making and implementation at the international and national level. The research will examine the micro-politics of the international negotiations and implementation of loss and damage policy and also involves cross-national comparative research on domestic loss and damage policy practices. Bringing these two streams of work together will allow me to show how and why policy practices shape the evolution of climate justice norms. CCLAD will also make an important methodological contribution through the development of political ethnography and “practice-tracing” methods.

1 471 530 €

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

The evolution from a stem cell to differentiated progeny underpins tissue development and homeostasis, which are driven by a multitude of cell fate choices. The transitions underlying these choices are not well understood. There are a number of challenges that must be overcome to achieve this understanding. In the proposed research we will tackle two of the challenges: first, the dynamics of fate choices, i.e. the dependence of transitions on time and inductive signals, remains cryptic; second, mechanical signalling regulates instructive cues for transitions but its role in the process is uncertain. One of the primary reasons these important aspects of cell fate choice remain a mystery is because the biology has not been coupled to the biotechnology appropriate to unravel it. This is the purpose of the proposed research: we will develop tools based in microfluidics, microfabrication and hydrogels and integrate them with our stem cell biology expertise to illuminate the process of cell fate choice. We will develop single cell microfluidic technology that possesses unprecedented temporal resolution and control over the signalling environment to study cell fate dynamics. We will also synthesize hydrogel substrates to exert complete control over the mechanical microenvironment of stem cells. Finally, we will advance tools to apply reproducible and defined forces to cells in order to study the role mechanical signalling in cell fate choice. Developing the proposed technology kit hand-in-hand with its biological applications will allow us to delve into the mechanisms of biological transitions in multiple stem cell systems, allowing us to uncover universal phenomena governing cell fate choice.

1 876 618 €

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

Humans are endowed with a number of advanced cognitive abilities not seen in other species. So what allows the human brain to stand out from the rest in these capabilities? In general, the brains of primates, including humans, have more neurons per unit volume than other mammals. But humans are also in the fortunate position of having the largest of the primate brains, making the number of neurons in the human cerebral cortex greatly expanded. Thus, the difference seems to be a matter of quantity, not quality. My laboratory is interested in understanding how neuron number, and thus brain size, is determined in human brain development. The research proposed here is aimed at taking an evolutionary approach to this question and comparing brain development in an in vitro 3D model system, cerebral organoids. This method, which relies on self-organization from differentiating pluripotent stem cells, recapitulates remarkably well the endogenous developmental program of the human brain. Having previously established the brain organoid approach, and more recently improved upon it with the application of bioengineering, my laboratory is in a unique position to carry out functional studies of human brain development. I propose to use this approach to compare developing human brain tissue to that of other hominid species and tease apart unique features of human neural stem cells and progenitors that allow them to generate more neurons and therefore a greater cerebral cortical size. Furthermore, we will perform transcriptomic and functional screening to identify factors underlying this expansion, followed by careful genetic substitution to test the contributions of putative evolutionary changes. In this way, we will functionally test putative human evolutionary changes in a manner not previously possible.

1 444 911 €

Start date: 2018-07-01, End date: 2023-06-30

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

2 081 747 €

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

Stellar evolution models are fundamental to nearly all fields of astrophysics, from exoplanet to galactic and extra-galactic research. The heart of the COBOM project is to develop a global physical picture of fundamental mixing processes in stars in order to derive robust and predictive stellar evolution models. The complex dynamics of flows at convective boundaries is a key process in stellar interiors that drives the transport of chemical species and heat, strongly affecting the structure and the evolution of many types of stars. The same physical processes can also drive transport of angular momentum, affecting the rotation evolution and the generation of magnetic field of stars. The treatment of mixing processes at convective boundaries (also referred to as overshooting) is currently one of the major uncertainties in stellar evolution theory. This mixing can dramatically affect the size of a convective core, the lifetime of major burning phases or the surface chemistry over a wide range of stellar masses. The main objectives of this project are to (1) develop a global theoretical framework to describe mixing and heat transport at convective boundaries in stellar interiors, (2) derive new physically-based transport coefficients and parametrizations for one-dimensional stellar evolution models and (3) test the new formalisms against a wide range of observations. We will accomplish these goals by performing the most comprehensive study ever performed of mixing processes in stars using a fundamentally new approach. We will combine the power of multi-dimensional fully compressible time implicit magneto-hydrodynamic simulations and rare event statistics, which are usually applied in finance or climate science. The key strength of the project is to establish a direct link between multi-dimensional results and observations (asteroseismology, eclipsing binaries, color-magnitude diagrams) via the exploitation of 1D stellar evolution models.

2 500 000 €

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

The objective of the project is to develop a computational approach to accelerate the discovery of molecular materials. These materials will include porous molecules, small organic molecules and macromolecular polymers, which have application as a result of either their porosity or optoelectronic properties. The applications that will be targeted include in molecular separations, sensing, (photo)catalysis and photovoltaics. To achieve my aims, I will screen libraries of building blocks through a combination of techniques including evolutionary algorithms and machine learning. Through the application of cheminformatics algorithms, I will target the most promising libraries, assess synthetic diversity and accessibility and analyse structure-property relationships. I will develop software that will predict the (macro)molecular structures and properties; the molecular property screening calculations will include void characterisation, binding energies, diffusion barriers, local assembly, charge transport and energy level assessment. A consideration of synthetic accessibility at every stage will be central to my approach, which will ensure the realisation of our predicted targets. I have several synthetic collaborators who can provide pathways to synthetic realisation. Improved materials in this field have the potential to either reduce our energy needs or provide renewable energy, helping the EU meet the targets of the 2030 Energy Strategy.

1 499 390 €

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

The fundamental objective of the research described in this proposal is to lay the foundations for understanding how structural complexity can give rise to materials properties inaccessible to structurally-simple states. The long-term vision is a paradigm shift in the way we as chemists design materials—the “Complexity Revolution”—where we move to thinking beyond the unit cell and harness unconventional order to generate emergent states with entirely novel behaviour. The key methodologies of the project are (i) exploitation of the rich structural information accessible using 3D-PDF / diffuse scattering techniques, (ii) exploration of the phase behaviour of unconventional ordered states using computational methods, and (iii) experimental/computational studies of a broad range of materials in which complexity arises from a large variety of different phenemona. In this way, the project will establish how we might controllably introduce complexity into materials by varying chemical composition and synthesis, how we might then characterise these complex states, and how we might exploit this complexity when designing next-generation materials with unprecedented electronic, catalytic, photonic, information storage, dielectric, topological, and magnetic properties.

3 362 635 €

Start date: 2018-10-01, End date: 2023-09-30

Light is generally expected to travel through media independent of its direction. Exceptions can be achieved eg. through polarization changes induced by magnetic fields (known as the Faraday effect) together with polarization-sensitive birefringent materials. However, light can also be influenced by the presence of a counterpropagating light wave. We have recently shown that this leads to the surprising consequence that light sent into tiny glass rings (microresonators) can only propagate in one direction, clockwise or counterclockwise, but not in both directions simultaneously. When sending exactly the same state of light (same power and polarization) into a microresonator, nonlinear interaction induces a spontaneous symmetry breaking in the propagation of light. In this proposal we plan to investigate the fundamental physics and a variety of ground-breaking applications of this effect. In one proposed application, this effect will be used for optical nonreciprocity and the realization of optical diodes in integrated photonic circuits that do not rely on magnetic fields (an important key element in integrated photonics). In another proposed experiment we plan to use the spontaneous symmetry breaking to demonstrate microresonator-based optical gyroscopes that have the potential to beat state-of-the-art sensors in both size and sensitivity. Additional research projects include experiments with all-optical logic gates, photonic memories, and near field sensors based on counterpropagating light states. Finally, we plan to demonstrate a microresonator-based system for the generation of dual-optical frequency combs that can be used for real-time precision spectroscopy in future lab-on-a-chip applications. On the fundamental physics side, our experiments investigate the interaction of counterpropagating light in a system with periodic boundary conditions. The fundamental nature of this system has the potential to impact other fields of science far beyond optical physics.

1 500 000 €

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

This proof of concept grant will revolutionise how bone marrow stem cells are cryopreserved by translating ERC-grant developed technology, inspired by how organisms survive in extreme cold temperatures. Bone marrow (haematopoietic) stem cells are used in life saving treatments, especially for blood cancers such as Leukaemia, but have potential for a wide range of diseases. The current method for storing stem cells involves addition of huge amounts of toxic organic solvents which leads to unwanted side-effects and not all the recovered cells are viable. There is also a rapidly growing market for stem-cell therapies, but with a major bottleneck being the logistics of transport: getting the cells from the (small number of) specialised production facilities to the patients, with minimum processing and within the cold chain. We have established strong preliminary data demonstrating an entirely new concept in cryopreservation based on the use of (patent pending) synthetic polymers, which can control ice formation and growth. These are inspired by how antifreeze proteins protect organisms which live in sub-zero environments, but with the advantages of being; Highly tuneable; Low toxicity; Scalable synthesis. This is backed up by demonstration of function in immortalised cell lines, and is ready to be applied to real biomedical problems. In this project we will obtain convincing data-sets demonstrating that our synthetic polymer can revolutionise the storage and transport of stem cells for current and emerging therapies. This will bring significant societal change through enabling new regenerative medicine therapies and bringing real commercial benefit by solving a supply chain challenge and improving on the current 50 year old method.

150 000 €

Start date: 2018-06-01, End date: 2019-11-30

This proposal (D5S) addresses a key problem of astrophysics – the origin of magnetic activity in the sun and solar-type stars. This is a problem not only of outstanding theoretical importance but also significant practical impact – solar activity has major terrestrial consequences. An increase in activity can lead to an increase in the number and violence of solar flares and coronal mass ejections, with profound consequences for our terrestrial environment, causing disruption to satellites and power. Predictions of magnetic activity are highly desired by government and industry groups alike. A deep understanding of the mechanisms leading to solar magnetic activity is required. The variable magnetic field is generated by a dynamo in the solar interior. Though this mechanism is known to involve the interaction of magnetohydrodynamic (MHD) turbulence with rotation, no realistic model for dynamo action currently exists. D5S utilises two recent significant breakthroughs to construct new models for magnetic field generation in the sun and other solar-type stars. The first of these involves an entirely new approach termed Direct Statistical Simulation (DSS) (developed by the PI), where the statistics of the astrophysical flows are solved directly (enabling the construction of more realistic models). This approach is coupled to a breakthrough (recently published by the PI in Nature) in our understanding of the physics of MHD turbulence at the extreme parameters relevant to solar interiors. D5S also uses the methodology of DSS to provide statistical subgrid models for Direct Numerical Simulation (DNS). This will increase the utility, fidelity and predictability of such models for solar magnetic activity. Either of these new approaches, taken in isolation, would lead to significant progress in our understanding of magnetic field generation in stars. Taken together, as in this proposal, they will provide a paradigm shift in our theories for solar magnetic activity.

2 499 899 €

Start date: 2018-10-01, End date: 2023-09-30

Classical dendritic cells (cDCs) are leucocytes that play a key role in innate immunity as well as the initiation and regulation of T cell responses. cDCpoiesis starts with commitment of a bone marrow (BM) haematopoietic progenitor, known as the classical DC precursor (CDP), to the cDC lineage. CDPs then give rise to pre-cDCs that exit the BM via the blood and seed tissues to give rise to the two major types of fully-differentiated cDCs, the cDC1 and cDC2 subsets. The key parameters of cDCpoiesis are poorly understood. We propose to characterise the niche in which cDCs develop within the BM and to study how pre-cDCs seed tissues and establish local clones of differentiated cDC1 and cDC2. We further wish to ask how the activity of CDPs and pre-cDCs is altered following infection, inflammation or tissue damage. Finally, we want to know to what extent cDCpoiesis is affected by direct sensing of infection or cell damage by cDC precursors. All these objectives will be addressed in a mouse lineage tracing model in which cDC precursors are genetically labelled through the activity of a Cre recombinase driven by the Clec9a locus. These mice will be crossed to fluorescent protein reporter mice, including Confetti mice that allow for clonal analysis, and the appearance of labelled cDCs and cDC clones in tissues will be followed over time in the steady-state or after induction of infection or inflammation. The dependence of cDC precursor activity on specific pathogen and damage sensing pathways will be assessed by loss-of-function experiments. The interactions of cDC precursors with their BM niche will be analysed in steady-state or inflammatory conditions by visualising the cells in situ. Finally, the consequences of demand-driven cDCpoiesis for immunity will be assessed. The results from this project will lead to a greater understanding of the influence of environmental signals on cDCpoiesis and may have applications in the design of better vaccines and immunotherapies.

2 500 000 €

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