NIHRDataInsights/HRCSData huggingface dataset:
Title: Making Light Deliver: translation of methods of photoporation
Funder: Engineering and Physical Sciences Research Council

Abstract: The cell membrane represents the outer extremity of all cells. In mammals, this is a thin bi-layer film of lipids, embedded with various protein molecules at interspersed locations. The membrane encloses the cell, defines its boundaries and maintains the essential physico-chemical differences between the cytoplasm and the extracellular environment. Under normal circumstances, the lipid nature of the cell membrane acts as an impermeable barrier to the passage of most water-soluble molecules. Thus, the selective introduction of therapeutic agents to the inside of dysfunctional or diseased cells remains a key challenge. The St Andrews-Dundee team's original Basic Technology grant was aimed at developing two inter-related strands of research that would enable targeted drug delivery to cells and tissue at will. The studies have resulted in excellent research and papers and the methods of using tightly focused laser beams to create minute transient pores that permit therapeutic agents to be introduced has been the most promising. This technique, termed photoporation, offers a powerful method for single cell targeted transfection in a sterile fashion. In this next proposal we aim to translate our results and the developed technology into devices that will be common place in both universities and industry. This will be because these optical devices will be able to deliver biologically important material, ranging from genes through to prototype drugs, into a host of different biological systems such as its involvement in stem cell research, plant cells, agriculture through to in vivo mammalian tissue.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Imperial College NDE Group - Renewal of Platform Grant
Funder: Engineering and Physical Sciences Research Council

Abstract: The main objectives of the current platform grant from 2005-2010 were for the group to expand into super resolution (sub wavelength) imaging, to increase our profile in the Structural Health Monitoring (SHM) field and to extend the scope of the group's modelling work. An important factor in attaining these objectives was expected to be staff stability and the ability to undertake feasibility studies in a timely manner. The objectives have been met in full, with the group developing a world leading position in super resolution imaging including major collaborations with key US institutions, doing exciting work in SHM that has led to the formation of a new spin-out company, and greatly enhancing our finite element modelling capabilities. The chief objective for the next period is to develop a modern ultrasound technology under the umbrella of quantitative imaging. In medical diagnostics we will combine quantitative imaging science with the new and exciting findings of biomechanics. Moreover, our international lead in NDE will enable us to cross-fertilise between medical and engineering applications to the benefit of both communities.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: GENERIC HEALTH RELEVANCE
Title: PROBING THE MECHANICAL CONTROL OF STEM CELL FATE THROUGH THE DEVELOPMENT OF NOVEL, NON-INVASIVE IMAGING TECHNOLOGIES
Funder: Engineering and Physical Sciences Research Council

Abstract: Whilst in our increasing ageing population stem cell science and technology holds a great deal of promise within the context of tissue repair and regeneration, moving this technology to the clinics has been relatively slow due to a number of distinct 'barriers'. For example, whilst we know a lot about the function and response of stem cells in the laboratory, we know very little about their behaviour in tissues within individuals. A further major barrier has been the inability to accurately track cell lineages and to distinguish them from other cell types within the tissue (i.e. when one cell divides to become two cells are they the same or different? Is this effect the same or different each time the cell divides? Where do they go?). This application will address these issues by bringing together researchers across different scientific disciplines in the physical and life sciences to develop novel technologies for stem cell science. Specifically, we will develop new ways of non-destructively labelling stem cells by manipulating molecules within the cells so we can follow both their position and their eventual fate (i.e. what do these stem cells turn into?). In order to image the cells we will develop new microscopic techniques that allow us to view these cells in a non-invasive, non-harmful way (unlike current approaches) and we will utilise technologies that will eventually enable us to image these cells deep within patient tissues. Being able to follow these stem cells will allow us to examine the mechanical influence of their surrounding tissue environments. Armed with such knowledge we will mechanically manipulate the surrounding environment to direct stem cells into our tissue of choice in order to deliver custom designed tissues on demand (either within the laboratory or eventually within a patient). Overall, our ultimate aim is to develop new tools to allow us to investigate and control stem cell biology in order to realise the true clinical potential of these cells.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Stem cell fractionation using interactions with artificial matrices
Funder: Engineering and Physical Sciences Research Council

Abstract: There has been a recent explosion in interest in and potential applications of stem cells. Their potential for therapeutic medical applications is particularly exciting, with the real prospect of growing replacement tissue and bone to overcome a wide variety of disease conditions. Stem cells also have an important role in diagnostics, and have already shown promise in drug discovery research. To date, the key limitation to the exploitation of stem cells has been their scarcity. Furthermore, even when it is possible to source stem cells, there is still the formidable task of purification and sorting of the usable cells from cells that have differentiated into unusable types. Presently, stem cells are labelled with markers and then sorted one-by-one using very expensive instruments. Despite the very high speed of modern cell sorters the relatively small numbers obtained and the addition of labelling reagents mean that these methods are not suitable for widespread application of stem cell therapy. Stem cells have yet to find global application, because of their rarity. This project proposes to change the current stem cell sorting methods from low throughput one-by-one techniques to very high throughput alternatives that will be capable of sorting millions of cells simultaneously. The key to this will be the design of a series of filters that behave as smart sieves. The stem cells will be poured through new filters that will recognise the cells by their shape, size, flexibility and their chemical signature, without the addition of any extra reagents. A set of filters will be assembled; one on top of the other, to allow rapid screening of a mixture that contains both the valuable wanted stem cells, alongside less useful cells. This research programme will focus on the design of these filter stages, and use cutting edge science and technology to generate a completely new approach to stem cell purification. Specialist techniques such as microfluidics, nanotechnology, rapid microstructure prototyping will be combined with the latest ideas in cell biochemistry and cell biorecognition to fulfil the primary objective of making it easier, cheaper and faster to harvest useful stem cells. The benefit to society will be huge, making the possibility of stem cell therapy a reality for everyone.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Enabling Tools & Technologies for Synthetic Biology
Funder: Engineering and Physical Sciences Research Council

Abstract: Synthetic Biology is a new discipline with the potential to create a wide variety of consumer products with applications in healthcare, biofuels, food, and materials. However, in order to realise its full potential, Synthetic Biology requires investment in fundamental research to develop basic protocols and technologies that allow researchers to quickly and easily make new biological parts and understand their behaviour in different conditions. We are an enthusiastic team of young researchers from different backgrounds in the Engineering, Physical and Biological Sciences who can use our combined expertise to tackle these problems This project employs a flexible funding model that allows us to adapt our research program as new information becomes available. Initially we have chosen to focus on five proof-of-principle projects that tackle the first steps in developing Synthetic Biology applications. We hope to answer the following questions:1) How can we improve DNA synthesis so that biological parts can be made more efficiently?2) Are there measurements that can be made outside of cells that will predict what will happen when nucleic acids and proteins are inside cells?3) Can we create non-living systems to test biological parts that do not interfere with their function?4) What type of measurement instruments will aid us in testing the behaviour of parts in different conditions?We will begin by answering these questions for a simple test system and use what we learn to develop methods for increasingly complex systems composed of more parts. As part of our research program, we will also consider how our work impacts society and ensure that interested parties learn about it by a series of activities including networking meetings, workshops, and public engagement activities.Not only is this work applicable to all researchers in Synthetic Biology, who will be able to more efficiently create new systems, but parts of it will also benefit researchers in other disciplines. For instance, new DNA synthesis technology will benefit researchers in all biological and medical disciplines who will no longer need to perform tedious molecular biology, but will instead be able to purchase genes of interest, accelerating the pace at which new discoveries are made. This, coupled with the discoveries that become possible from synthetic biologists means our work has a wide ranging impact.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Analytical Methods For Certain Inverse Problems In Medical Imaging
Funder: Engineering and Physical Sciences Research Council

Abstract: A variety of medical imaging techniques are based on the solution of a class of mathematical problems, called inverse problems In particular, in the medical imaging techniques of Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT), the associated inverse problems involve the inversion of the Radon transform and of the so-called Attenuated Radon transform, respectively. Although an analytical formula for the former transform is well known, an analogous formula for the latter transform was obtained only recently. We will develop further analytical algorithms based on the above formulae and on non-smooth-norm de-noising strategies. Furthermore, by employing a variety of clinical data, we will compare the new algorithms with commercial software.The medical techniques of Magnetoencephalography (MEG) and Electroencephalography (EEG), also involve the solution of certain inverse problems In a recent breakthrough, the PI has presented a comprehensive solution of these inverse problems We will develop further the relevant algorithms, we will use the techniques of reproducing kernels for their numerical implementation, and we will compare them with commercial software using a variety of real data.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Warwick Complexity Science Doctoral Training Centre 2
Funder: Engineering and Physical Sciences Research Council

Abstract: It is a key challenge for our society to better understand, adapt, design and control complex systems A complex system comprises many interacting components leading to multiple levels of collective structure and organization. Examples include natural systems ranging from bio-molecules and living cells to human social systems and the ecosphere, as well as sophisticated artificial systems such as the Internet, power grid or any large-scale distributed software system. Ongoing Research Themes:Complexity, Emergence & Upscaling. In mathematically oriented research we attempt to crystallise clear and appliable definitions of information content and emergent behaviour.Complex Fluids and Complex flows. How do a small fraction of interacting particles conspire to dominate their flow properties, and how do those properties influence particular flows? Clustering, Condensation and Jamming. Clustering phenomena are ubiquitous with applications ranging from raindrops to galaxies, and from facebook to traffic jams Complex Networks & their dynamics. The interplay between the connectivity of a network and its dynamics are central to key challenges today, such as epidemiology, biodiversity, neuroscience and markets. Network Statistical Inference. The inference of network structure is a key approach we use in applications spanning multiple fields, from molecular biology to health and economics. New Applications of Statistical Mechanics. This well developed set of tools finds fresh use in molecular biology, traffic theory and opinion dynamics. Developing Areas include:Complex Systems in Social Science, Epidemiology and related Ecology, and Bioimaging.National Need.The financial crisis shows how urgently the UK needs people trained to understand systemic risk in a complex socio-technical system and to design regulation and incentives to get the economy going again. The debate on climate change shows how vital it is to the UK to have people trained in understanding the implications of policies on a large complex socio-economic-physical-biological system. Our partner BAS (British Antarctic Survey) explicitly recognises Complexity as a divisional aspect of their organisation: Natural Complexity Programme. The debate about management of the National Health Service shows how important it is to involve trained people in designing the incentive and monitoring system. The advances in ability to monitor gene expression provide a huge opportunity for people trained in discerning patterns to contribute to controlling many diseases, particularly cancer. The advances in ability to monitor brain activity create huge opportunities for people trained in understanding network function to contribute to controlling malfunctions such as epilepsy, Parkinson's disease and Alzheimer's disease.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: GENERIC HEALTH RELEVANCE
Title: From Targeted Therapeutics to Next-Generation Medicines
Funder: Engineering and Physical Sciences Research Council

Abstract: The need for innovation in healthcare is a key EPSRC priority, recognising that improvements to the health of UK citizens require step changes in the science and technology underlying diagnosis and treatment. Collaborative research, linking the engineering, physical and life sciences across academy and industry, and supported by the research councils, has been a crucial factor in establishing the UK pharmaceuticals sector as second only to the US in the discovery of new medicines. In this proposal we set out an extension and enhancement to the UK's first pharmaceutical sciences Doctoral Training Centre (DTC) joint-funded by industry, the EPSRC/AstraZeneca Doctoral Training Centre in Targeted Therapeutics. The first four years of the Targeted Therapeutics DTC have seen the successful establishment of 20 new collaborative PhD programs with AstraZeneca, 27 papers, patents or conference contributions, 35 new training projects and a vibrant community of highly talented multidisciplinary research students. A total of 15.1 million in grants related to Targeted Therapeutics has been awarded to DTC project leaders since 2006 and 43 principal researchers are now working together across the University of Nottingham and four AstraZeneca sites. To build on the successes of this unique centre we now seek to extend the DTC further into exciting new science and training programs that address the emerging needs of the pharmaceuticals sector in predictive science, complex formulations and biotherapeutics. As a School we are already investing strongly in the 'Next Generation Medicines' area, with new staff positions and studentships. We now request funds from the EPSRC initially to train a further cohort of 5 PhD students over 4 years, with a view to establishing connecting scientific projects prior to a bid for 2 extra cohorts in 2011. The timing for this two-stage bid is crucial owing to recent changes in AstraZeneca and the closure of their Loughborough site, as it will bridge a funding gap as the company consolidates its core science areas. The extension of the Targeted Therapeutics DTC into a new Centre for Doctoral Training will prepare UK scientists to be in the forefront of the international industry as it introduces the sophisticated therapies forming the 'next-generation' family of targeted and personalised medicines.


Research activity codes: 5.1 PHARMACEUTICALS;5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: Next Generation Analytical Tools: Application to Protein Oxidations that affect Human Health and Wellbeing
Funder: Engineering and Physical Sciences Research Council

Abstract: New and novel measurement tools and technologies enable modern biological and biomedical research to continue to move forward at a rapid rate. Detecting disease and evaluating the effects of drugs all rely on measurement technologies, and the limitations in our ability to measure things rapidly, accurately and cheaply is often the bottleneck in many research areas. Similarly, advances in industrial processes and clinical methods are often dependent on matching advances in measurement technology. In this programme two leading research centres from Glasgow University and Imperial College London join forces to develop new techniques and tools in order to improve existing approaches to detect and quantify the effects of protein oxidative damage in biological samples. Protein oxidative damage is one of the components of ageing and can cause a range of serious medical problems As part of this project we will improve the ways in which biological samples are delivered into a range of analytical platforms such as mass spectroscopy and protein microarrays by employing novel innovative approaches such as acoustic sound waves, emulsion droplets and microfludics. Chemical tools and probes that seek out and detect damaged proteins will be constructed and subsequently incorporated into the technologies mentioned above. These technologies will be used to study the dynamics of protein damage in space and time. Another part of the programme develops high throughput analysis tools of various forms all of which use minaturisation methods to allow for the analysis of as many proteins as possible, as rapidly as possible and with as much detail as possible. It is anticipated that this multidisciplinary programme will create the necessary analytical platforms to overcome a technological gap that is holding back biological and medical discoveries in this research area that is vital for fostering our understanding of human health and ageing. It also has the potential to facilitate medical interventions to alleviate the symptoms of ageing and age-related illness. Given the importance of these issues for the general population, not just of the UK but worldwide, the impact of this programme will be significant and sustained for several years in terms of academic output as well as industrial wealth generation. In particular, novel drug targets and indeed drugs, as well as improved diagnostic techniques to monitor and assess human health and ageing are possible outcomes in the near future. Given the importance of oxidative damage in crop production it is likely that our programme will also produce tools that benefit the agrochemical industry, making this proposal a truly discipline crossing venture with respect to the sciences involved and the impact generated.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: A new approach to Science at the Life Sciences Interface
Funder: Engineering and Physical Sciences Research Council

Abstract: The key scientific challenges of the next century require that we fundamentally advance current understanding of complex natural systems - ranging from how cells work and why/how they go wrong, to how the interaction of climate and ecosystems regulates the planet's life support system. We wish to understand how these systems behave at the functional level, and how this behaviour arises as a result of highly dynamic, strongly non-linear, tightly coupled interactions between component processes occurring across multiple spatial and temporal scales. Entirely new kinds of exploratory and predictive models and research strategies are needed to address these challenges. A new generation of theoretical methods and tools are needed to enable the recognition and exploitation of synergies and similarities that allow the translation of solutions between different scientific problem domains. Biological theories are evaluated against often imperfect data sets. There is a need for judicious selection and validation of the test bed against which any model is evaluated and the development of novel technologies for gathering new data identified as critical to complex system behaviour. The investigation of systems-level behaviour requires the identification of biological hypotheses that could not have been expressed by looking at individual phenomena alone. The unprecedented degree of complexity will mean that these quantitative models will be analytically intractable, and exploring their behaviour will be possible only through a computational approach. In short, a novel computational approach and environment is needed for doing this kind of science - and this does not exist in academia today. Progress requires both a cultural and technological change in the way in which mathematical and computational models, tools and software are developed, and a concomitant change in the way in which groups of scientists are trained to develop and use these approaches. This work can only be done in the context of real biological problems This proposal brings together a consortium of partners from academia and industry, each of whom has begun to focus on differing but complementary aspects of these problems These centres are the ideal community to attempt such a cultural shift since they are already dedicated to training the next generation of scientists who will pioneer this kind of science.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: GENERIC HEALTH RELEVANCE