3,142 Projects, page 1 of 629
Programme overview: This MRC-funded doctoral training partnership (DTP) brings together cutting-edge molecular and analytical sciences with innovative computational approaches in data analysis to enable students to address hypothesis-led biomedical research questions. This is a 4-year programme whose first year involves a series of taught modules and two laboratory-based research projects that lead to an MSc in Interdisciplinary Biomedical Research. The first two terms consist of a selection of taught modules that allow students to gain a solid grounding in multidisciplinary science. Students also attend a series of masterclasses led by academic and industry experts in areas of molecular, cellular and tissue dynamics, microbiology and infection, applied biomedical technologies and artificial intelligence and data science. During the third and summer terms students conduct two eleven-week research projects in labs of their choice. Project: Autophagy, which literally means 'self-eating', is an essential process that involves the degradation of cytoplasmic material. This homeostatic process enables cells to reutilise materials and produce energy when conditions become unfavourable or to clear damaged cellular components or remove specific proteins if they are over-produced. Dysfunction in autophagy has been implicated in many diseases such as cancer and bacterial and viral infections. Autophagic activity declines with age and so has been associated with the development of age-related diseases, such as neurodegeneration. It is thus important to develop interventions that maintain autophagic activity through the life course. Natural products from Streptomyces bacteria produce many metabolites of therapeutic interest. For example, Rapamycin is a natural product from Streptomyces that induces autophagy. However, Rapamycin also has unwanted side effects such as immunosuppression. Thus, there is a need to identify additional natural compounds that can be produced in large quantities but without lack such side effects. The aim of this project is to isolate and characterize additional novel natural compounds that can activate autophagy. Specifically, the student will Isolate novel natural compounds from diverse culture extracts prepared using Streptomyces species using a range of analytical chemistry techniques including LC-MS, HPLC and NMR spectroscopy for structural elucidation, combined with bioinformatics to predict the nature of the compounds of interest. The student will then test if these compounds activate autophagy in larva and adult flies of Drosophila models of human neurodegenerative disease. The molecular and cellular pathways stimulated by pro-autophagic compounds will be characterized further in mammalian tissue culture cells.
Analytical Science involves the development and application of new methods to measure the composition and structure of manufactured and natural substances of all types. The analytical sector in the UK underpins many vital industries (e.g. food, chemical, pharmaceutical, environmental, materials), is crucial to process and cost control, to product quality and competitiveness, to industrial compliance with environmental and safety legislation, and to the delivery of healthcare and justice. Crucially, progress in Analytical Science is also essential to advances in many key research areas including materials and life sciences. Modern analytical problems often require high spatial resolution in three dimensions, resulting in very large, complex data sets. Moreover, there is a need to combine information from multiple data sets of very different provenance. Recent official reviews have warned that, despite its central importance to the UK's economic and scientific competitiveness, Analytical Science in the UK suffers from low esteem and fragmentation, and lacks interdisciplinarity. The result is a shortage of analytical scientists, and an alarmingly low level of innovation compared to other countries. Research and innovation-led reinvigoration of this area is essential for the UK's economic and social well-being. The University of Warwick invests heavily in multidisciplinary research and education, and has a strong research base in Analytical Science in the Departments of Chemistry, Physics, Statistics, Engineering, Biological Sciences and the Medical School. Building on this philosophy, we have responded to the fourth Science and Innovation Call by proposing lectureships in three new interdisciplinary research areas (Chemometrics and Experimental Design, Chemical and Structural Characterisation of Materials, and Mass Spectrometry) that will be combined with diverse research in Analytical Science at Warwick to found a new Centre for Analytical Science, expected to boost the profile of Analytical Science in the UK and world-wide. Recognising the fact that scientific progress crucially depends on communication and collaboration between different disciplines and sectors, a central aim of the Centre will be to bring together people from academia and industry with the objective of providing a platform for identification, definition, and implementation of new Analytical Science research goals including the development of new instrumentation, and new methods for data acquisition and statistical inference. The process of innovation requires a dialogue between academia and the private sector. As stated in the Lambert report, the best forms of knowledge transfer involve human interaction . Therefore, the Centre will have an academic/industrial Advisory Board, and will develop, through its new Analytical Forum, a visitor and outreach programme, not only to enable the exchange of ideas, knowledge, and technology between developers and users of analytical tools in public and private sectors, but also to foster new collaborations.Applicants of the very highest quality will be attracted by offering excellent research facilities supported by PhD students and post-doctoral researchers in a well resourced multinational, multidisciplinary environment. The Centre will develop training programmes in Analytical Science, statistics and transferable skills. The integration of research and education in the Centre will offer a comprehensive approach to Analytical Science, helping to provide the UK with the skills base essential to remain internationally competitive.Warwick will nurture the new Centre by guaranteeing long-term support for the area, and by investing heavily in state-of-the-art equipment, purpose-built accommodation and infrastructure. There will be development of modules for CPD, PG and UG training which will help sustainability.
Tau is a protein that is highly expressed in nerve cells in the brain and helps to maintain their shape and function. In conditions like Alzheimer's disease (AD), tau molecules can join together to form aggregates. These aggregates disrupt nerve cell function and can alter the pathways that underlie learning and memory. For example, they can make neurons more excitable and disrupt how they can communicate with one another. In this project, the effect of tau aggregates on different nerve cell types will be evaluated. This interdisciplinary project will combine training in both experimental electrophysiology (a way to measure nerve cell activity and communication between nerve cells) with the implementation of computational models of neuronal network activity. The student will be trained in machine learning, data analysis and modelling which also directly meets the MRCs quantitative skills theme. The student will be trained in the following: Identification of different nerve cell types using specialised imaging techniques Electrophysiological recordings from single and multiple nerve cells Data analysis and mathematical modelling of neuronal function and network activity Understanding the mechanisms by which tau aggregates alter network activity will help to generate new targets for better and more effective treatments of diseases like AD in the future.
Every human cell is encased by a cell membrane that separates the cell contents from its surroundings. Proteins embedded in this membrane act as gates to allow molecules to enter and exit cells; they also mediate the interactions that occur between a cell and its environment. This means that membrane proteins are involved in many of the most fundamental processes in normal cell function; when these processes fail, diseases result. It is no surprise, then, that the top ten best-selling small molecule drugs of all time all target membrane proteins. There are many different membrane proteins in any given cell, grouped into over 1,500 families, each with many members. In order to study any of them in detail, it is important to understand their three-dimensional structures. Central to this is a technique called X-ray crystallography that allows scientists to obtain a detailed view of how the atoms within a protein are arranged, providing a framework for further study. Scientists use this framework to investigate how the protein functions, bringing new levels of understanding to how cells work in health and disease, and providing knowledge to develop new drugs. Tetraspanins are membrane proteins that function by interacting with a wide range of other membrane and soluble proteins, thereby affecting how cells signal, interact, change shape and move. Remarkably, tetraspanins are also involved in the process of infection for a wide range of diseases. However, because there is no known structure of any full-length tetraspanin family member, the mode of action of tetraspanins in these essential processes is not understood, leaving a major gap in our knowledge of cell biology. Obtaining the structure of any membrane protein is a major scientific challenge: It is necessary to remove the protein from the cell membrane which often results in the protein becoming so unstable that it cannot be used to make the crystals required to perform X-ray crystallography. Consequently, we know very little about many membrane protein families with important biological functions. We have now overcome this crystallization challenge for the tetraspanin, CD81. Human CD81 is one of the best understood tetraspanin family members and is the subject of our proposed research. It has well-established roles in how cells interact with each other, the immune response and fertilization. Notably CD81 is a receptor for some very important human pathogens including influenza, human immunodeficiency virus, the malarial parasite, T-cell lymphotropic virus type 1 and hepatitis C virus (HCV). It may also be a tumour promoter. Central to CD81 function (and to that of all tetraspanins) is its ability to form extensive interactions with itself and other proteins; however, we don't know what these structures look like and therefore lack the framework for further study, mentioned above. The first aim of the research outlined in our proposal is to solve the three-dimensional structure of CD81. We have made excellent progress towards this goal, having crystallized CD81 and collected X-ray diffraction data. We have also teamed up with scientists in France who can make soluble forms of the HCV protein, E2, that binds CD81. The second aim of our project is to make an HCV-E2/CD81 complex so we can characterize it and solve its structure; this will allow us to learn more about how CD81 interacts with other proteins. We believe we are the only team in the world that has all the tools to take on this challenge. Brand new developments in structural biology (e.g. high-resolution electron microscopy) have enabled us to devise a third aim, which is to look at these structures in the cell membrane (by electron tomography), linking our atomic level structural data to what is actually happening in the cell. Studying the structure of CD81 at this level of detail will allow us to begin to understand how tetraspanins work in health and disease.
JM, Oxford University, Ilika and WMG propose a collaboration to jointly develop a high energy density protected anode material for Li-sulphur batteries, as a low cost alternative to traditional lithium-ion. The project will evaluate protection mechanisms for anode materials. Without the protective layer, anode materials show little reversible capacity. These protected anodes give a much higher cycle life that can compete with traditional LiB (~500-1000 cycles at least before 80% initial capacity is reached). This is an innovative energy storage solution to be used in conjunction with renewable energy harvesting, with around three times more energy density than the current technology. Storing electrical energy from renewable energy sources in battery banks for release at peak times has the benefit of reducing CO2 emissions. In addition, with the higher volumetric energy envisioned using this technology, LiSBs will have the potential to be used in electric vehicles which has previously been the reserve of Li-ion technology. The main advantage to using LiSBs over LIBs is the higher energy density, which can lead to lower cost per Wh. This can give LiSBs the market opportunity for implementation in future application in the stationary energy storage and automotive sector. Oxford will screen and develop solid electrolyte materials with optimum ionic conductivity for protecting the lithium anode. This work will involve synthesis of ceramic electrolytes and will be carried out in combination with the high throughput-PVD techniques of Ilika. In parallel, fabrication of composite structures of protective layers for the anode will be created in collaboration with Ilika and JM. Evaluation of best-performing solid electrolytes to be employed for protecting the anode will subsequently take place in order to focus on analysis of the protection mechanism. A deeper understanding of the interfacial phenomena, occurring in the protected anode will be further investigated through both electrochemical and microstructural analyses such as galvanostatic/potentiostatic polarisation or cycling, EIS, SEM, XPS and X-ray CT. In this project the WMG will utilise facilities and technologists within its partly government funded Energy Innovation Centre (EIC) which has been established to provide both industry and academia alike with a capability to use emerging battery chemistries in multi-scale formats from research scale through to representative prototype sizes. The EIC features electrode mixing and coating equipment incorporating the latest technology for producing high quality, consistent electrodes. JM are experts in material development and have recently demonstrated that cell performance of their cathode material in Li-S prototypes is comparable and competitive with commercial Li-ion cells in terms of cycle life, energy density and rate capability. The partners will advance the performance of current LiSBs technology by developing high energy density protected anode materials -imperative for pushing LiSBs onto both the stationary energy storage market and into the automotive industry. The WMG will work directly with JM and Ilika to develop the high energy protected anode composites and also optimise the Li-S electrodes in conjunction with Oxford for both high energy and cycle life. The aim of the research is to provide new anode and cathode materials for high energy LiSBs, which will surpass performance levels of the commercialised Li-ion graphite systems. The benefit to the academic community is the dissemination of practical research which has the capability of accelerating the uptake of LiSB technology into a high value manufacturing environment. The commercialisation strategy is to licence the Li-S technology IP to material and battery manufacturers.