Most human disorders are complex and involve a multitude of genes, environmental inputs, and change in prevalence with age. To understand such disorders clinical researchers often use a specific set of lab animals (model organisms) that display similarity to human disease. However, while this approach has provided major advances for understanding some of the causal mutations underlying human disease there can be limitations in terms of how translatable results are. This is often attributed to differences between humans and other animals but it may also be the result of the approach used. Normally, lab-based research on such model organisms standardizes environmental conditions, as well as genetic variation within a lab line. This can simplify comparisons with an 'all else being equal' approach that allows for single mutations to be compared (i.e. this is often referred to as the mutant model approach). However, as mentioned above, many diseases manifest themselves from a multitude of genes, environments, and age. An emerging alternative to the traditional mutant model approach is now arriving from nature where in some cases evolutionary adaptations can actually resemble human disease. What is particularly exciting in that such populations can be more in line with how humans live, in that they experience environmental variation, and often have a diversity of genetic variation. Thus, they could be particularly effective for understanding complex human disease. This project will take advantage of a natural set of populations of fish, specifically threespine sticklebacks experiencing warmed habitats as a result of geothermal activity in Iceland. Such warmed habitats present a unique challenge to these fish as the higher temperature raises their metabolism, including in winter when prey are limited. This appears to have caused 'energy-sparing' adaptations to evolve in these fish, such as increased fat deposition, indications of glucose tolerance, and higher appetites. This can be considered to resemble metabolic syndrome in humans, but it is unclear what underlying mechanisms determine these changes, and whether a wider suite of traits are involved. To determine the utility of this system as a model for human disease will require deeper investigation, but could be especially valuable if these fish have also evolved the mitigate the negative effects of these traits. Therefore, we will aim to ascertain how the body composition of these fish is determined using a comprehensive approach that accounts for genetic, epigenetic, and environmental cues. This approach should more closely match how traits are determined in nature and lead to accurate insights about their mechanisms. We will also assess further aspects of the metabolic divergence between geothermal and ambient populations of stickleback, including glucose and insulin tolerance. Lastly, we will examine whether the expected negative effects of metabolic syndrome occur with associated traits in sticklebacks. Specifically, we will look for signs of non-alcoholic fatty liver disease, and test whether blood concentrations of triglycerides and cholesterol occur in geothermal fish (which would be expected to occur with higher levels of body fat). We predict that geothermal fish will show signs of mitigating these negative effects, and if supported it could provide the basis for further insight and even therapies for humans.

Microorganisms are the most abundant life forms on Earth. It is estimated that there are around 10 thousand, billion, billion, billion individual organisms belonging to two main microbial groups (the bacteria and archaea). This is 1 million times more than the estimated number of stars in the known Universe. It is believed that most of this vast population is found in deep sediments far below the ground and the sea floor. It is easy to think that this huge repository of buried biological (microbial) diversity is irrelevant to mankind, but nothing could be further from the truth. This intra-terrestrial microbiota has been coined the 'deep biosphere' and it is central to the cycling of matter over geological timescales. Of more immediate concern is the role that certain deep biosphere organisms have played in modifying oil in situ in petroleum reservoirs. Most of the world's oil (e.g. the giant tar sand deposits in Western Canada) has been degraded by microbes in situ long before humans recovered the first drop of crude oil. Research from our group has uncovered the microbial processes responsible for crude oil biodegradation in petroleum reservoirs and identified biological and geological factors that promote biodegradation. One of these factors is temperature. The temperature of the Earth's crust increases with depth by approximately 2-3 C every 100 meters and petroleum reservoirs at temperatures above 90 C are not subject to biodegradation. However cooler, shallower reservoirs are not always biodegraded. These non-degraded, cool shallow reservoirs once resided at greater depths but have been moved by geological uplift to shallower depths. It appears that they are not re-colonized by oil-degrading bacteria and the oil in these reservoirs remains intact. This process of transient heating of a petroleum reservoir which kills the resident oil-degrading microbiota has been termed palaeopasteurization. Research in the Arctic has provided a window into the petroleum reservoir deep biosphere. Cold Arctic sediments harbour bacteria that have optimal activity at around 50 C and may have come from leaky warm petroleum reservoirs because their closest relatives were previously identified in hot oil wells. These organisms form spores which are highly resistant to environmental extremes and act as survival capsules that protect the bacteria on their journey from deep within the Earth. These bacteria thrive without oxygen (anaerobes) and the spores resist exposure to oxygen. Sediments in the UK harbour spore-forming bacteria that degrade crude oil without oxygen, providing another link between bacteria and petroleum reservoirs. This project aims to determine if spore-forming oil-degrading and Arctic bacteria ultimately derive from petroleum reservoirs and if the process of palaeopasteurization kills them and prevents them seeding surface sediments. The project focuses on fundamental science at the interface between biology and geology and has practical implications. A supply of hydrocarbon degrading anaerobes from the deep biosphere has implications for microbial diversity in surface sediments where these bacteria may play a role in oil clean up in oxygen depleted sediments (i.e., in coastal sediments but also the deep Gulf of Mexico seafloor near the Macondo wellhead). Related bacteria also cause problems in the oil industry by producing the toxic gas hydrogen sulphide in a process known as reservoir souring. This reduces the value of oil and poses a hazard to workers. The UK hosts a major offshore oil industry that contributes significantly to employment and economic prosperity. During the transition between a fossil carbon energy economy and a renewable energy economy, the need remains for innovative operational practices to reduce the environmental impact of oil production and exploration; much of this is underpinned by an understanding of microorganisms associated with oil production and oil degradation in the environment.

As the global climate warms, thawing permafrost may lead to increased greenhouse gas release from Arctic and Boreal ecosystems. Scientists agree that this permafrost-climate feedback is important to the global climate system, but its magnitude and timing remains poorly understood. The overall aim of COUP is to use detailed understanding of landscape-scale processes to improve global scale climate models. Better predictions of how permafrost areas will respond to a warming climate can help us understand and plan for future global change. In recent years much scientific progress has been made towards understanding the complex responses of permafrost ecosystem to climate warming. Despite this, large challenges remain when it comes to including these processes in global climate models. Permafrost ecosystems are highly variable and studies show that very detailed field investigations are needed to understand complexities. Because global scale models cannot run at such high-resolutions, we propose an approach where local landscape-scale field studies and modelling are used to identify those key variables that should be improved in global models. We will carry out careful field studies and high-resolution modelling at field sites covering all pan-Eurasian environmental conditions. The system understanding gained from this will then be used to (1) scale key variables so they are useful for global models and (2) improve a new global climate model. In the final step, the improved global climate models will be run to quantify the impact of thawing permafrost on the global climate. Datasets produced in COUP will be freely available online so that they can be used by other scientists and help improvement of all global climate models. COUP is designed to maximise synergies with ongoing projects. Much of the needed data and system understanding was generated in other research programmes.

Between the fourth and the sixth centuries exile was a legal sanction frequently used by Roman emperors and the rulers of the post-Roman successor states against dissident Christian clerics. This project seeks to test the hypothesis that such exile proved to be not only a form of punishment, but also, and more importantly, a form of cultural encounter. Clerics in exile spread their ideas at places where they had previously been unknown. They also absorbed influences from their new environment and, in the case of recall from exile, transferred ideas and experiences elsewhere. This process, the project contends, had a profound impact on the development of Christianity and its foundational texts in this period, which are still noticeable today. For example, the Nicene creed, which most of modern Christian denominations subscribe to, may not have had the same impact without the banishment of its original supporters during the fourth century. In order to prove its hypothesis, the project adopts an interdisciplinary approach with an innovative methodology. It is a collaboration between Dr Julia Hillner (Sheffield, PI), a legal historian, and two international co-investigators, Prof Jörg Ulrich (Halle), a theologian, and Associate Prof Jakob Engberg (Aarhus), a cultural historian. While both the development of Christian theology and ritual in this period and the legal development of the Roman penalty of exile have been extensively studied, the two have not been brought together before. The project seeks to rectify this gap in scholarship by re-invigorating traditional legal and theological studies that have typically concentrated on normative sources through the application of a digital approach that will help to set these sources in context. To this end, the project includes the construction of a relational database that collects all available information on individual clerical exiles. The data will be derived from printed and online source editions and we anticipate a dataset comprising records for approximately 1,000 individuals. This will allow the project team to trace and visualise the personal and geographical networks clerical exiles developed and maintained from their place of banishment and after return from exile. The quantitative information will provide the basis for a thorough qualitative re-assessment of selected legal, theological and hagiographical texts of the period (also available in edited form), which will be investigated in the light of the networks of their authors and audiences. This part of the project will seek to establish the influence of exile experiences on the formation of Christian law, Christian doctrine and Christian cult in late antiquity. In short, the project involves a long-term study of exile that focuses on social networks of individual clerics and interprets institutional texts and structures not according to a top-down model of change, but as a result of relations among individuals, facilitated by exile, within a decentralised framework, in which every element of the network contributed to shape institutional developments. The results of the project will be disseminated via a book co-authored by the PI, the Co-Is and the research associate of the project, and via a doctoral dissertation. The project will also maintain a project blog and website, which will ensure access to the database for a larger academic audience, and, embedded in educational material, for a broader non-academic audience, and will hold a final international conference. The project will also develop a network of local museums and heritage organisations at places of late antique banishment with a view to develop closer collaboration for future funding applications. The project will commence in May 2014 and is scheduled to run for 36 months.

Number Theory is the study of the integers and their arithmetic applications. While problems in Number Theory can be easy to state, their solutions often become extremely intricate. For example, Fermat's Last Theorem - was formulated in the 17th century, yet only resolved in the 1990's. A fundamental approach in mathematics is to transform a seemingly difficult problem from one area to another, where it becomes tractable or even obvious. A famous example, is Wiles' proof of Fermat's Last Theorem; the key change in perspective transforming a problem about certain arithmetic objects (Galois representations of elliptic curves) into one about analytic objects (modular forms). This correspondence established by Wiles completing the proof of Fermat's Last Theorem is a very special case of a broad web of predicted correspondences and connections between analysis and arithmetic, collectively known as the Langlands Programme. The Local Langlands Programme is the specialization of the Langlands Programme at a prime number, and this is where the bulk of the research of our project takes place. The language of the Local Langlands Programme is in a branch of Algebra called Representation Theory, which deals with symmetries of spaces. The Local Langlands Programme is a deep statement that certain fundamental symmetries of finite dimensional spaces which arise in Number Theory can be understood in terms of completely different symmetries of infinite dimensional spaces, and conversely. The finite and infinite dimensional spaces considered are built on top of the complex numbers. A natural question now arises, why the complex numbers? Is there a more fundamental arithmetic connection hiding behind this? In this project, using explicit constructions of representations, we study integral structures in the Local Langlands Programme and their relation.