Epidemic models for pathogens transmitted from human to human are, naturally, concerned with the interaction between individuals that leads to transmission. This is clearly a major simplification; there are many processes at work, from the feedack loop of epidemics on behaviour and interventions, to resource constraints limiting the production of prophylaxis and availability of diagnostic tests, to the response of the immune system to the pathogen and pharmaceuticals. Epidemic models do not normally include an account of these highly influential processes. Instead, only the assumed effect of these processes is sometimes included. This strongly limits the scope of epidemic models. By contrast, in molecular biology, it is typical to consider a much larger class of possible interactions. There exist methods as well as mature software for expressing and simulating systems with many interactions. We have successfully shown that these techniques can be fruitfully applied directly to epidemics, including in a multi- scale setting incorporating immune response and, with suitable extensions, to detailed epidemic reconstruction in a complex community setting. We will build on this success in order to consolidate this capability within the infectious disease modelling community. We will improve accessibility of the tools that we used in our pioneering work, facilitating adoption of our epidemic modelling methods more widely. We will foster a community of practice by conducting a series of case studies to establish documented and standardisable approaches to bringing our advanced techniques to bear on pressing current and future questions relevant to reducing the public health burden of infectious disease.

Describe the research in simple terms in a way that could be publicised to a general audience. This will be made publicly available, and Applicants are responsible for ensuring that the content is suitable for publication. No more than, 4000 characters including spaces and returns. Seismic hazards endanger both human lives and critical infrastructure, underscoring the need for a more profound understanding of earthquake dynamics and precise risk assessment, especially in regions prone to infrequent, long-recurrence events. Globally, earthquakes predominantly cluster along tectonic plate boundaries, where heightened seismic risk is acknowledged despite the lack of precise information on location and timing of earthquakes. Conversely, intraplate regions, situated away from these boundaries, also experience significant earthquakes, presenting a distinct challenge due to their rarity. Notably, these seismically active intraplate regions often coincide with large urban centres, amplifying potential risks. Key features that distinguish interplate and intraplate earthquakes include (1) variations in the stress on the fault that drives slip; (2) earthquake magnitude-frequency distributions - the number of small earthquakes in a region relative to large earthquakes; and (3) source parameters that dictate the severity of an earthquake, including the stress drop, duration of the event, and precursory phases that occur immediately preceding earthquakes. Investigating these distinctions and the underlying reasons responsible for them, as well as documenting historical earthquake events, holds promise for both a more comprehensive understanding of earthquakes and a pathway to enhanced regional seismic hazard assessment. Our project is dedicated to exploring the fundamental physics of earthquake rupture and documenting historical earthquakes within the Indian subcontinent including the public and state response to these events. These endeavours are inextricably linked and involve distinguishing the characteristic features between interplate and intraplate regions through a combination of laboratory experiments, borehole stress measurements, and seismic monitoring, and developing better records of historical seismicity and the response to it. By scrutinizing stress conditions, rock properties, earthquake magnitudes, source characteristics, and infrequent historical events, we aim to elevate the precision of risk analysis in key regions within India. The knowledge gained from these activities will be brought together to craft an educational and outreach initiative aimed at both the general population (through schools) and local government through education on the scientific and historical nature of earthquake hazard and development of tools to improve decision making. The program will heighten public awareness regarding earthquake risks, promote straightforward life-saving measures, and develop better planning to prepare and deal with future seismic hazard.

When we learnt classical thermodynamics from undergraduate physics/chemistry, we often assumed a large number of particles ~10^23, equilibrium, and quasi-static process. In this very restrictive limit, thermodynamic quantities such as heat dissipation Q, can be computed using the textbook formula Q= T\Delta S, where S is the configurational entropy. However, in real lives, most physical processes are neither quasi-static nor equilibrium. Furthermore, in many biological systems, the number of degrees of freedom is also much less than 10^23, and in this regime, thermal fluctuations become important. Thus, thermodynamic quantities such as heat, work and entropy need to be redefined properly (Stochastic Thermodynamics). The first aim of this research is to extend the theory of stochastic thermodynamics to include birth and death process, e.g., cellular division and apoptosis in living tissues and growing bacterial colonies. One important application of stochastic thermodynamics is the prospects of biological machines, which are powered by the swimming motility in some bacteria, or even cellular division and apoptosis in our bodies. For instance, it has been well known experimentally and theoretically that if we place an asymmetric cog inside a bath full of swimming bacteria, the cog can somehow rotate persistently in one direction. The bacteria themselves, in the absence of the cog, swim in a completely random direction; and yet the interaction between the bacteria and the asymmetric cog can break time reversal symmetry to create a macroscopic unidirectional current. Although this phenomenon has been well established in motile active matter (such as swimming bacteria), very little is known about non-motile growing active matter (such as cell division and apoptosis in living tissues and bacterial colonies). In this research, I will explore cellular division and apoptosis as a new route to the development of biological machines. This is important because unlike cell motility, cell division and apoptosis are universal properties of living matter. My design principles for such machines will pave the way for future possible applications in healthcare technologies and tissue engineering, such controlling the growth of tissue using non-uniform scaffolding. Finally, I will investigate the thermodynamic properties of these machines. In particular, I will quantify the informatic entropy production of the birth and death process inside biological tissues and bacterial colonies, i.e., particles dividing into two and disappearing elsewhere. To achieve this, I will extend the current theory of stochastic thermodynamics to include birth and death process and stochastic processes that are much faster than quasi-static (i.e., quenching). This information will be crucial in understanding how time reversal symmetry breaking at small scales (i.e., cell cycle) can be translated into large scales (i.e., collective motion in tissues and bacterial colonies). Apart from obvious applications to active/living matter, my research will also help to transform the science of thermodynamics, such as understanding the energy flow in a quenching process and/or processes close to a critical point, where thermal fluctuations are important.

Development of materials has underpinned human and societal development for millennia, and such development has accelerated as time has passed. From the discovery of bronze through to wrought iron and then steel and polymers the visible world around has been shaped and built, relying on the intrinsic properties of these materials. In the 20th century a new materials revolution took place leading to the development of materials that are designed for their electronic (e.g. silicon), optical (e.g. glass fibres) or magnetic (e.g. recording media) properties. These materials changed the way we interact with the world and each other through the development of microelectronics (computers), the world wide web (optical fibre communications) and associated technologies. Now, two decades into the 21st century, we need to add more functionality into materials at ever smaller length-scales in order to develop ever more capable technologies with increased energy efficiency and at an acceptable manufacturing cost. In pursuing this ambition, we now find ourselves at the limit of current materials-processing technologies with an often complex interdependence of materials properties (e.g. thermal and electronic). As we approach length scales below 100s of nanometres, we have to harness quantum effects to address the need for devices with a step-change in performance and energy-efficiency, and ultimately for some cases the fundamental limitations of quantum mechanics. In this programme grant we will develop a new approach to delivering material functionalisation based on Nanoscale Advanced Materials Engineering (NAME). This approach will enable the modification of materials through the addition (doping) of single atoms through to many trillions with extreme accuracy (~20 nanometres, less than 1000th the thickness of a human hair). This will allow us to functionalise specifically a material in a highly localised location leaving the remaining material available for modification. For the first time this will offer a new approach to addressing the limitations faced by existing approaches in technology development at these small length scales. We will be able to change independently a material's electronic and thermal properties on the nanoscale, and use the precise doping to deliver enhanced optical functionality in engineered materials. Ambitiously, we aim to use NAME to control material properties which have to date proven difficult to exploit fully (e.g. quantum mechanical spin), and to control states of systems predicted but not yet directly experimentally observed or controlled (e.g. topological surface states). Ultimately, we may provide a viable route to the development of quantum bits (qubits) in materials which are a pre-requisite for the realisation of a quantum computer. Such a technology, albeit long term, is predicted to be the next great technological revolution NAME is a collaborative programme between internationally leading UK researchers from the Universities of Manchester, Leeds and Imperial College London, who together lead the Henry Royce Institute research theme identified as 'Atoms to Devices'. Together they have already established the required substantial infrastructure and state-of-the-art facilities through investment from Royce, the EPSRC and each University partner. The programme grant will provide the resource to assemble the wider team required to deliver the NAME vision, including UK academics, research fellows, and postdoctoral researchers, supported by PhD students funded by the Universities. The programme grant also has significant support from wider academia and industry based both within the UK and internationally.

Context The Southern Ocean plays a critical role in the Earth system. It hosts emblematic components of global biodiversity that motivate international conservation efforts. It is also the flywheel of the ocean circulation and climate system, where it plays a critical role in the carbon sequestration and supplies nutrients to lower latitudes where they support global productivity. These key ecosystem services are supported by the activity of photosynthetic phytoplankton and zooplankton that underpin food-webs and biogeochemical cycling. We need accurate climate-model projections to assess the response of Southern Ocean ecosystems and biogeochemical cycles to climate change. But our best models cannot even correctly reproduce the direction of ongoing change. This suggests fundamental problems with projections, undermining efforts to protect and conserve ecosystems and lowering confidence in our understanding of how carbon and nutrient cycling will respond, both in the future and in the geological past. Iron-Man will develop a new paradigm that integrates the processes regulating Southern Ocean productivity by addressing critical knowledge gaps. This is urgent given the rapid ongoing changes to the region and the timescales of policy action that require robust science. Challenge we address Over past decades, extensive research has focused on the role of the micronutrient iron (Fe) in the Southern Ocean. However, recent work, spanning observations, experiments and models (mostly led by our team), now shows that accounting for manganese (Mn) as a limiting nutrient and the associated unique ecophysiology of the resident phytoplankton community is also critical to the ecological-biogeochemical function of the Southern Ocean. Importantly, these issues are neglected by current models. Iron-Man is focused on unravelling how the supply and cycling of Fe and Mn affects the net primary productivity (NPP) and biomass of Southern Ocean ecosystems. In doing so, we will deliver 'fit for purpose' assessments of how future change will affect this critical system. Aims and objectives We have assembled a team of world leading scientists, operating across multiple disciplines, using state-of-the-art observational, experimental and modelling tools in an integrated and co-designed manner. Iron-Man must address three questions: 1. How the relative supply of Fe and Mn varies to set the resource limitation regime? 2. How phyto- and zoo-plankton in different regions respond to changes in Fe and Mn? 3. Whether integrating Mn and regional ecology alters future projections? These are mapped onto three objectives: 1. Quantify the relative supply and abiotic recycling and removal of Fe and Mn to the upper ocean varies in different regimes, using ship-based and autonomous platforms. 2. Assess biological cycling of Fe and Mn, alongside the adaptive and acclimatory responses via integrated measurements across natural gradients and manipulative experiments. 3. Produce improved model projections of NPP and ecological change in the Southern Ocean and test the importance of newly identified knowledge gaps. Potential applications and benefits International experts acting as partners will maximise our ability to upscale and engage stakeholders with our results. We focus specifically on key international initiatives (e.g. CCAMLR, CMIP7 etc) and science-to-society challenges, including co-financing of stakeholder facing events and outputs throughout the project duration. In this way, Iron-Man will make critical contributions to the scientific knowledge base around the response of the Southern Ocean in a changing climate, but also make a difference by translating science for the policy makers grappling with a rapidly changing system.