• 2013-2022close
• UK Research and Innovation close
• 2014 close
• 2018 close

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

This FRL project is concerned with how rising immigration and increasing ethnic diversity affect social cohesion. The UK is currently undergoing a significant demographic shift in the ethnic composition of its populace, with the proportion of non-White British rising from 13% to 20% between 2001 and 2011. Across academic, governmental and public spheres, concerns are being articulated that this growing diversity poses a threat to: residential community cohesion (undermining trust and connectivity between neighbours); wider, societal cohesion (leading to civic disengagement, declining trust in strangers and lower support for welfare policies); and inter-group cohesion (cultivating inter-ethnic tensions, and driving support for far-right organisations). When even conservative estimates predict this trend will only increase, understanding if, how and why ethnic diversity affects social cohesion, and what can be done to ameliorate any pejorative effects, is of paramount importance to the maintenance of a cohesive, harmonious society. Yet, significant gaps remain in our understanding of how of ethnic diversity affects social cohesion. Firstly, much of the current research focuses on how being exposed to diversity within one's residential community affects social cohesion. However, the community is just one site at which individuals come into contact with other ethnic groups. In places like schools, universities, workplaces, volunteering groups, individuals are being exposed to diverse environments everyday. However, how levels of diversity in these places affect social cohesion is largely unknown. This is an important omission given that individuals are actually more likely to encounter diversity in these places than in their neighbourhoods. Secondly, most research assumes that as diversity within an adult's neighbourhood increases, their social cohesion will shift accordingly. However, how adults respond to ethnically diverse environments is likely influenced by all kinds of experiences throughout their lives, such as the attitudes of their parents, the diversity of their schools, and how diverse the neighbourhoods were they grew up in. To understand how diversity affects social cohesion we therefore also need to know what individuals' experiences of ethnic diversity have been over their entire lives. The primary aim of this research is therefore to try and create a much fuller picture of how ethnic diversity affects social cohesion by: firstly, looking at how coming into contact with other groups in schools, workplaces, or civic groups, along with neighbourhoods, affects cohesion; and secondly, how experiences of diversity over one's whole life affects cohesion. Only with this more complete picture of the complex social worlds of individuals can we hope to understand the effect of diversity on social cohesion. However, if we do find that increasing diversity, in certain places, at certain points over an individual's life, can harm social cohesion, then we need to know 'what works' to ameliorate such frictions. This research will therefore investigate how interventions, such as intercultural education, workplace diversity training, national multiculturalism policies, and ethnic mixing programs for adolescents can help alleviate any pressures of increasing diversity. Key to this endeavour will be an analysis of one of the current government's key integration policies: the National Citizen Service.

Sarcopenia is an age-related loss of skeletal muscle mass and strength. It is characterised by muscle fibre atrophy (decreased muscle fibre size) and reduced muscle function linked to increase of the presence of non-muscle cells, like fat, within the muscle and disrupted muscle repair. Sarcopenia leads to poor balance, falls and fractures and increased morbidity and mortality in our ageing population. As the ageing population increases, it is important to identify the mechanisms responsible for this age-related muscle loss. The molecular factors responsible for sarcopenia are not fully understood, however changes in the expression of genes have been implicated in sarcopenia. MicroRNAs (miRNAs, miRs) are small RNA molecules that regulate gene expression. Each microRNA is predicted to regulate the expression of up to several hundred genes. Expression of numerous microRNAs and their target genes changes with age or in diseases. This makes microRNAs very strong candidates for therapeutic targets for sarcopenia and other age-related disorders, for example by controlling their levels by using molecules that mimic their behaviour. In preliminary data the applicant has shown that that the levels of microRNAs, important for muscle function, change in muscle with age. This new research proposes that the age-related changes in microRNA abundance are a major contributing factor to the muscle loss process. Using cell culture and model organism systems, the levels of these small molecules (microRNAs) will be manipulated in muscle cells and tissues and the effects on muscle wasting will be examined. Concurrently, the potential of miRNA-based intervention to prevent, delay or treat sarcopenia will be established. The first objective will determine the set of muscle-specific microRNAs that are changed in the muscle tissue of old mice compared with adult mice. The second objective will confirm important microRNA target genes in muscle and characterise the details of the interactions of microRNAs and the specific genes they regulate in the context of loss of muscle mass and function. The final aim of the project will examine the potential of microRNA mimics and antagomiRs (small molecules that increase or decrease of the microRNA levels, respectively) in preventing age-related loss of muscle using a mouse model organism. This project is important to strengthen our knowledge about the molecular basis of sarcopenia and is likely to lead to the design of novel therapeutic approaches to prevent, delay or treat age-related skeletal muscle wasting.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at www.rcuk.ac.uk/StudentshipTerminology. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

In computer science the reachability is one of the fundamental problems taking its roots from the first undecidable decision problem in the computability theory - termination/halting problem in Turing Machine: "Given a description of an arbitrary computer program, decide whether the program finishes running or continues to run forever" or "Deciding, given a program and an input, whether the program will eventually halt when run with that input, or will run forever". In the modern world software is now everywhere (in almost all devices including phones, cars, planes, etc ). The solution of the reachability problem: "Deciding whether a particular piece of code will reach a bad state, can avoid some execution path or will eventually terminate" is the core component of the verification tools that can grantee the reliability of the code and correct functionality of complex technological devices. The proposed research of this project is mostly in the study of reachability problems for classical mathematical objects such as words, matrices, iterative maps and aims to get a progress with a solution of challenging and fundamental long standing open problems in mathematics and computer science, which also appear in the analysis of natural processes in physics, chemistry, biology, ecology, economics etc. The primary goal of this project is to demonstrate that it is possible to go significantly beyond known results related to reachability problems in matrix semigroups, iterative maps and related word problems by applying a combination of techniques from computational theory, number theory, algebra and combinatorics on words. Our principal objectives within this research programme are: identifying new classes with decidable reachability problems for words, matrices and maps, designing efficient algorithms for decidable cases and estimating their computational complexity. First, we propose to study generalized model that cover originally independent, but closely related open problems and investigate the reductions between them. Then we suggest following three approaches to get a better understanding of the core problems: investigation of topological properties of the reachability sets and their application for reachability analysis; translation of matrix reachability problems into combinatorial and computational problems on words; and the design of semi-algorithms for reachability problems in higher dimensions based on projection methods, where infinite reachability set can be mapped into various finite structures which preserve some of the reachability properties. The result of the project would be twofold. In relation to reachability problems for matrices and maps, we expect that new deep results related to open problems will be obtained by applying a combination of techniques from computational complexity theory, automata and formal langauges, algebra, number theory and combinatorics on words. At a more general level we expect to establish new direction of research connecting challenging problems in mathematics with theoretical computer science structures, methods and results. The list of indirect and long-term beneficiaries is not limited to developers of software verification techniques and algorithms, but also includes a variety of specialists in physics, chemistry, biology, environmental sciences and economics which require efficient tools for predicting the behaviour of the complex systems represented by matrices and matrix products.

The behaviour of cells within a tissue is controlled by their response to the environment. Receptor molecules at the cell surface receive a large number of chemical and physical stimuli that transmit signals to the interior of the cell and control important processes such cell migration, metabolism, cell proliferation and differentiation. Anomalies in the transmission of such signals result in pathological states that derive in diseases like cancer, diabetes, muscular dystrophy and neurological degeneration. Amongst the most important signals that cells receive are from circulating small proteins called growth factors. These bind to specialised receptors, that in response to growth factor engagement alter their pattern of interactions with many molecules inside the cell to generate a so-called 'mitogenic response'. This response encompasses many changes to the cell's behaviour (such as growth, division and migration). One of the best-studied examples of a growth factor receptor is the epidermal growth factor receptor (EGFR), which controls many aspects of cell growth. Increased expression of EGFR is linked to several types of cancer. In order to prevent overstimulation of the cell response to growth factors, there are mechanisms of regulation to ensure that these responses are not sustained endlessly, which would lead to uncontrolled cell division and proliferation. These mechanisms encompass the internalisation of the receptor upon stimulation, leading it from the cell surface to specialised membrane-enclosed compartments within the cell (called endosomes). From endosomes, receptors pass to another membrane-enclosed compartment called the lysosome, where they are ultimately destroyed. The pathway to the endosome is termed the endocytic pathway. We discovered key elements of the cellular pathway that controls the uptake of EGFR and its movement through the endocytic pathway. These elements recognise the stimulated receptor and re-shape the local membrane around it so that the receptor can move from the cell surface to endosomes and then to lysosomes. The current application concerns a new protein element that we have discovered, called LITAF. Our preliminary data suggest that LITAF can alter the shape of membranes and thus aid the transport of EGFR through the endocytic pathway. The endocytic pathway is also critical in protecting against viral and bacterial infections and to eliminate protein aggregates that otherwise accumulate inside cells and result in the neurodegeneration observed in Alzheimer's, Parkinson's and Huntington's diseases. In fact, LITAF (lipopolysaccharide-induced TNF factor) was first identified as a protein that the cell produces in high quantity as a response to exposure to bacterial toxins. It is likely that the function of LITAF is linked in some way to the function of the endocytic pathway in helping to generate immune responses, though we do not yet know what the link is. In addition, mutations within LITAF that occur in the population lead to a debilitating paralysis termed Charcot Marie Tooth disease, caused by loss of myelin sheaths from the peripheral nervous system. We hope that information we gain from this project will help us understand how the health of the myelin sheath is normally maintained In summary, the knowledge gained by our investigations will bring new insights into the molecular basis of many diseases caused by mutations in proteins that control the endocytic pathway, and in the long-term will guide further efforts for pharmacological intervention.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at www.rcuk.ac.uk/StudentshipTerminology. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at www.rcuk.ac.uk/StudentshipTerminology. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

The gastrointestinal tract is a vital organ that converts our diet into useful digestible nutrients, contributes to the maintenance of water balance and protects our body from pathogenic microorganisms that are present within the lumen of the gut, along with large numbers of beneficial bacteria. In order for the gut to carry out its essential functions, it contains exquisitely specialised cells, including epithelial cells, immune cells, nerve cells and muscle cells. Intestinal epithelial cells are tightly connected to each other to form a sophisticated gatekeeping system that allows the selective transport of nutrients and water but keeps away harmful toxins or pathogenic bacteria. Immune cells constantly monitor the lumen and the wall of the gut and respond in case the essential intestinal barrier is breached. Finally, complex networks of nerve cells within the gut wall are responsible for generating intestinal movements that are essential for proper digestive function by activating the musculature of the gut wall. Since the intestinal epithelium is constantly exposed to harmful substances and pathogenic microorganisms, it is quite vulnerable and is often damaged. Normally this does not have detrimental consequences for an organism since all cells of the intestinal epithelium are continuously replenished by stem cells that are dedicated to producing constantly fresh epithelial cells. Although the continuous regeneration of the intestinal epithelium is essential for maintaining it in good working order, other cell types play a major role in keeping them healthy. In particular, glial cells, which normally accompany and support nerve cells in all parts of the nervous system, are also found in the vicinity of intestinal epithelial cells and release substances that are essential for maintaining the intestinal epithelial barrier; if these enteric glial cells are eliminated in experimental conditions, the barrier breaks down and animals die from acute inflammation of the small intestine. In addition, several studies have suggested that the inflammation that accompanies common gut diseases, such as Crohn's disease or ulcerative colitis, may also involve the abnormal interaction of glial cells with intestinal epithelial cells and immune cells. These observations support the idea that despite their specialised functions, the different cell types that make up the gut wall (and indeed any organ) need to work in concert in order to support its physiological roles. Despite the important roles of the intestinal glial cells in supporting the critical functions of the nerve cells and the epithelium of the gut, very little is known about their biology in healthy individuals and in disease situations. In this proposal we will aim at filling this knowledge gap by building on some of our own recent observations. In particular, we will identify and characterise the properties of the gliogenic stem cells which generate new glial cells throughout life. We will also identify conditions and signals that modulate the behaviour of intestinal glial cells. Finally, we plan to characterise molecules which are located within the nucleus and are important for these cells to maintain their properties and continue to generate new glial cells throughout adult life. Normal digestive function depends on the fine balance between the loss of old and the production of new cells in the different gut tissues and the optimal cross talk between the different cell types. Breakdown of such an equilibrium results in uncontrolled growth of cells (cancer), severe inflammation of the gut wall (inflammatory bowel disease-IBD) or inability of the gut wall to protect the internal environment of an organisms from toxic substances or pathogenic bacteria. Understanding how local glial cells contribute to the integrity and normal function of gut tissues, we can ultimately use these cells as a means to alter the course of common debilitating gastrointestinal disorders.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at www.rcuk.ac.uk/StudentshipTerminology. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.