NIHRDataInsights/HRCSData huggingface dataset:
Title: Fibre Optic Sensors for Point of Care health Diagnostics
Funder: Engineering and Physical Sciences Research Council

Abstract: Enhanced prediction and diagnosis in real time and at the point of care is recognised as a means of addressing national and global health challenges, with the development of sensors to detect and measure biomedical markers being a strategic priority. Chem


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Moving the goal posts: PARASHIFT proton magnetic resonance imaging
Funder: Engineering and Physical Sciences Research Council

Abstract: Magnetic resonance imaging (MRI) offers a window on the human body and reports the relative distribution of water in tissues within the body. MRI scans are used around the world with about 100 million examinations per year, and in 40% of these cases a contrast agent is given to the patient to assist in image clarity, aiding the radiologist in interpreting the scans observed. The scanner is tuned to the frequency at which the water hydrogen nuclei resonate, which lies in the radiofrequency range. We propose to develop a series of safe, well tolerated contrast agents that can be observed in parallel to observation of the water signal. These contrast agents, based on rare earth metal complexes, will possess a reporting proton signal that can be observed far away from the water signal, typically at least 10 kHz away, allowing it to be selectively observed. By careful design of these systems, we will make the probe resonant frequency sensitive to local physiological parameters, such as pH or the local extracellular concentration of certain essential metal ions like magnesium and calcium. This will allow these parameters to be assessed in the region of interest that is observed. Such work is important as different regions have differing local pH gradients, and changes in extracellular calcium concentration is important in assessing bone disorders. The physiological and pathological role of magnesium is believed to be very important in stroke and ischemia, but no such real-time measurements of its levels have been made before. A key aspect of this 'dual imaging' approach is that the new contrast agents can be detected at much lower concentration, and at levels that are safe to use. These levels lie within the current range of the approved gadolinium contrast agents that have been used clinically since 1988. This enhanced sensitivity arises from the closeness of the reporting proton signalling group to a magnetic metal centre that is incarcerated within the contrast agent. This proximity leads to enhanced sensitivity because the signal acquisition sequence can be speeded up, allowing signal intensity to be acquired about 20 times faster than would otherwise be possible.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Total syntheses of vioprolides for further biological evaluation
Funder: Engineering and Physical Sciences Research Council

Abstract: Human cells have various processes to protect themselves from bacterial and viral infections. Some of these processes are mediated by signalling pathways that alert the cell to a threat and initiate a response. Interferon mediated pathways are essential for cell defence. The NF-kB pathway is linked to inflammation and specifically to chronic inflammatory bowel disease in humans. These pathways can be influenced by a range of "small" molecules and the study of how such compounds can activate or moderate these pathways is of considerable interest in the context of understanding them more thoroughly and with the development of new therapies for a range of viral and inflammatory diseases. The vioprolides are a group of modified cyclic peptides isolated from a myxobacterium that have been shown to have a synergystic activating effect on an interferon mediated pathway in cells and a moderating effect on the NF-kB pathway. Unfortunately the quantities of vioprolides that are available from the natural source are very limited indeed and are restricting further studies into the biological effects of these compounds. It is proposed to develop syntheses of these vioprolides from simpler commercially available compounds so that the biological studies can be resumed. Moreover once these syntheses are complete, it should be possible to modify them to provide analogues of the naturally occurring compounds in order to study aspects of the effects of structural changes on the biological activities of these compounds. These syntheses will be challenging in themselves although by using a convergent approach it is hoped that the longest linear route will be no more than 20 steps long. The syntheses will not be straight forward since embedded within the structures of the vioprolides are features that made them very sensitive to certain chemical reagents. However, based on preliminary studies an approach to these compounds has been put forward and will be the basis of the work to be carried out with the support of this grant. Finally, it should be noted that the vioprolides are active at the nanogramme level. So the synthesis of tens of milligramme quantities should provide enough material for biological studies to continue although it it hoped to prepare at least one vioprolide on a hundred milligramme scale.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Manufacturing Green Nanoparticles for Efficient Cell Manufacture
Funder: Engineering and Physical Sciences Research Council

Abstract: Material-cell interface, which strongly depends on surface and materials properties, can augment cell growth and is extremely useful in enabling exquisite control of cellular manufacturing. We will address challenges related to the total efficiency of the


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Development of an optical system for on-line tracking of cell growth on microcarriers
Funder: Engineering and Physical Sciences Research Council

Abstract: In order that people can live longer and lead more active lives there is a need to develop novel affordable and effective treatments for ill health. In some cases, cells that we have within our own bodies can be used to repair damaged tissues or organs. However, in adults, this repair mechanism is very limited and often inefficient so we may need to rely on cells from donors. Unfortunately, since it takes billions of cells to repair, for example the heart muscle of a heart-attack patient, we must isolate cells from donors and expand their numbers before they can be used for treatment. So far we can do this at the laboratory scale, generating for instance, millions of mesenchymal stem cells in a stirred tank over a period of 2 weeks. However, as we consider how this will be achieved on a bigger manufacturing scale, we need to develop tools that will help us monitor and control the process to ensure the cells grown in this way are the same every time - just as we would expect other medicines to be identical from batch to batch. This feasibility project aims to combine the expertise of both biologists and engineers, to create an optical device that can monitor the growth of these cells in this stirred tank environment by giving the operator information about cell number and morphology. If successful, it will help optimise growing conditions so enough cells to treat multiple patients can be manufactured consistently.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: EuroTracker Dyes: Synthesis and Application in Functional Cell Imaging
Funder: Engineering and Physical Sciences Research Council

Abstract: The visualisation of certain living cells or microbes by optical microscopy requires the introduction of bright, luminescent dyes or stains, that can light up selected parts of the cell effectively. We will develop bright complexes of the rare earth element, europium, (EuroTracker dyes) as optical probes that emit light efficiently and report information back to the observer about their chemical or biological environment. These probes have been designed to allow them to be excited by the light sources that are available in microscopes used by physical scientists, biochemists and cell biologists, to study the interior composition of cells or related small compartments. By examining series of closely related probes, we shall define systems that locate to a particular compartment of a cell, allowing it to be visualised selectively. The optical probes that are currently used are based either on organic compounds, on large man-made proteins or on so-called quantum dots; each of these probes suffer from problems of low chemical stability, a tendency to fade and, in certain cases, they are rather toxic to the living cell. Thus we aim to change the thinking of the microscopy community and to pave the way for such emissive metal complexes to be used as stains and probes in biology. These metal complex probes emit light over longer timescales than conventional probes, and so their is more time to collect the emitted light after pulsed excitation and only short exposure times to the light that is used to excite them. The long emission lifetime avoids problems in data acquisition that are associated with light scattering and background autofluorescence. In parallel, we shall develop instrumentation methods that allow the spectral signature of these probes to be recorded quickly using fast imaging methods. We shall work with microscope manufacturers and with optics specialists to this end. This will allow changes in chemical composition within a cell to be tracked on a 10 second timescale. As a first step, we shall develop probes that can report on pH change and on the amount of sodium, magnesium and zinc within a specific cell compartment, allowing changes in the amount of these important metal ions to be tracked in living cells in real time. By adopting a modular approach to probe design, different metal ions can be examined subsequently, by introducing the appropriate metal-binding moiety into the probe structure.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Intelligent Manufacturing of Pharmaceutical Film Coating Using Terahertz Pulsed Imaging, Optical Coherence Tomography and Numerical Modelling
Funder: Engineering and Physical Sciences Research Council

Abstract: Functional coatings are highly engineered drug delivery systems whose structure and composition is critical to the controlled release of the active pharmaceutical ingredient in the human body. This increase in manufacturing complexity coincides with a tim


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE
Title: Monetize Me? Privacy and the Quantified Self in the Digital Economy
Funder: Economic and Social Research Council

Abstract: Lifelogging and self-quantifying used to be niche areas for athletes, people with certain medical conditions, and those with the time, money, and motivation to use expensive specialist equipment to monitor themselves. Now the technology for ordinary people to track and analyze many aspects of their lives is becoming both affordable and invisible, requiring little effort or expense to collect. There are many business models based on mining the so-called 'digital exhaust' of people's online activity to provide apparently free services. The fact that so many more people are now able to automatically log so many aspects of their lives (beyond which web pages they visited) is creating opportunities for new business models to actually provide services for the people generating the data. For example, some people may wish to sell their data for cash rather than give it away, some may wish to donate it to worthy scientific causes, such as health research, while others may wish to share data only in a non-identifying aggregated form or perhaps not at all. Lifelogging data can range from relatively benign (such as number of keystrokes typed in a day) to the highly personal (such as the emotional arousal state) and the ways in which the data is shared may be highly nuanced. This project seeks to understand how the privacy and sharing requirements vary across different demographic groups and to build a sharing and privacy infrastructure specifically designed for lifelogging data.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE
Title: Scale up of optical fractionation for bio-processing
Funder: Engineering and Physical Sciences Research Council

Abstract: Human pluripotent stem cells are the primary template cells for nearly all the cell types within the body. The exclusivity of these cells arises from their unmatched capability to remain in an unspecialised state until they are induced to differentiate (c


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES;5.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Computational Challenges in Biochemical Networks: Multiscale Modelling and Inverse Problems
Funder: Engineering and Physical Sciences Research Council

Abstract: In the last 20 years, technologies have been developed which allow biologists to observe, in real time, the reactions which are occurring in a single cell. These new developments have the potential to give us a whole new understanding of how cells function. In particular, it gives us a tool with which we can make great leaps in our understanding of how our genes operate and affect the way cells behave, multiply, and die. The understanding of these mechanisms is key in developing treatments for conditions for when they go wrong, for instance in cancer. As such, this relatively young area of science could be very important for the future of the health of humankind. The use of these technologies is increasing rapidly amongst biologists, but the problem remains as how best to interpret this data, and allow us to understand what we have observed. What is more, the observational methods are far from perfect, and are full of small errors which could cloud our conclusions. Therefore it is important that we understand the underlying mathematics within these problems, in a bid to extract as much reliable information from this data as possible. The aim of this project is to study the mathematical theory behind, and develop new computer algorithms for, the analysis of this type of data. The Bayesian philosophy is a mathematical framework which allows us to not only identify likely biochemical mechanisms which could have caused the phenomena we observe in the experiments, but also to quantify how much we should believe our own results. This project will have significant impact on this area, and help to cement the UK's position as one of the leading places to conduct biological and pharmaceutical research, which plays such an important part in our economy. Furthermore, it will enhance the UK's reputation for high quality interdisciplinary applied mathematics research.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: GENERIC HEALTH RELEVANCE
Title: Computer-aided design of degradable Mg-based metallic glasses for safe medical implantation
Funder: Engineering and Physical Sciences Research Council

Abstract: As human life expectancy continues to lengthen, there will be an increased number of implants in human bodies. The growing biomaterials field can already produce artificial teeth and skin, cochlear implants, artificial corneas, coronary stents and artificial hips, among others. As our need for implants grows, there is a continuing drive to improve the materials from which they are made. Magnesium-based metals and alloys are often used for orthopaedic implants, because they have similar mechanical properties to human bone, and they dissolve to components already present in the body. In the past, they have caused problems because they release hydrogen gas when placed in the body, which can be harmful and needs to be removed. Certain compositions of Mg-based metallic glass containing zinc and calcium, do not release hydrogen, and so, providing they retain the appropriate mechanical properties, they are much more suitable for use as biomedical implants than existing materials. The aim of this project is to use computer modelling to design and optimise these Mg-based metallic glasses for safe implantation into the human body. Advances in computer simulation mean that it is now possible to investigate the structure of complex materials such as these ternary metallic glasses. The molecular dynamics (MD) simulations we will use will reveal the atomic structure and the nature of the chemical bonds which exist in the glass. In the glass compositions which do not release hydrogen, a passivating layer is known to form on the surface of the glass when it is implanted in the body, but only for certain compositions of the glass. We will construct accurate models of the bulk and surface properties of these glasses, as well as those of related compositions. MD simulations will provide atomic-level resolution of the structure of the glass, and we will use this to identify the features which control the formation of the surface layer, and the release of hydrogen, and understand how these can be controlled. We will also model the interaction of the glass surface with the physiological environment, to gain a full understanding of the reactions which occur in the body. Through the simulation of a wide range of glass compositions, and full analysis of the compositional dependence of the surface layer, we will be able to deduce what reactions cause the formation of the passivating layer, and inhibit the release of hydrogen. Once we understand the features which control the formation of the surface layer, we will optimise Mg-based metallic glasses for use in biomedical implantation, by computational design of suitable glass compositions which have the appropriate mechanical properties but also do not release hydrogen. This will lead to the design of improved and safe implants for biomedicine, especially in orthopaedic applications.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Difluorocarbene: Synthesis, Reactivity and Applications for PET Imaging
Funder: Engineering and Physical Sciences Research Council

Abstract: Positron Emission Tomography (PET) is a non-invasive quantitative imaging technology that can detect pre-symptomatic biochemical changes in body tissues where no evidence of abnormality from computed tomography (CT) or Magnetic Resonance Imaging (MRI) are detectable or before structural changes occur from disease. This technology helps researchers understanding diseases and can assist clinicians in the selection of the best treatment for an individual patient, provided that competent biomarkers are available. The unrivalled sensitivity of PET makes this technique also suitable to address questions fundamental to drug development for oncology, cardiology, neurosciences and inflammatory diseases. One of the most commonly used positron-emitting radioisotopes is 18F, in part due to the extensive use of [18F]fluorodeoxyglucose in the clinic and the importance of fluorine substitution in the context of drug discovery. The short half-life of 18F (110 min) dictates a preference for protocols based on late stage fluorination. The enabling technology that underlies all forms of [18F]radiotracer imaging is [18F]radiotracer chemistry, because it is required for the development of [18F]radiotracer probe molecules. Radiotracer chemistry is a unique discipline that demands special reactions, equipment, techniques, understanding, and training. Its uniqueness stems from the unique behavior of chemical reactions conducted at the tracer-level scale to obtain products of sufficiently high specific activity, the need for efficiency and speed associated with performing chemical transformations and product purifications on materials that are labeled with short half-life radionuclides such as [18F]. The aim of this project is to develop new [18F]radiochemistry with the view to access much needed [18F]radiotracers currently difficult or not possible to prepare. We propose several methods to [18F]label molecules containing CF3 and CF2 motifs commonly found in pharmaceutical drug candidates and biomarkers. The project based on solid published preliminary data exploits the reactivity of difluorocarbene and easily accessible [18F]fluoride used in combination with readily available precursors and co-reagents. The emphasis is on the development of [18F]radiotracer chemistry methods that are versatile and easy to translate from molecule to molecule to advance the field of PET imaging in the UK and abroad.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Physical role of the nucleus in cell migration
Funder: Engineering and Physical Sciences Research Council

Abstract: Understanding how metastatic cancer cells move will enable the search for therapies targeting secondary tumour forming cells. Recent experiments suggest that the cell nucleus, which is disrupted and generally much softer in cancerous cells compared to healthy cells, plays an important role in cell migration. Specifically the nucleus is thought to be involved in setting or maintaining the direction of cell motion. Connections between the nucleus and the cytoskeleton (the main structural body of the cell) appear to be essential for migration in soft 3D tissue-like environments. Finally whether or not the nucleus gets stuck determines whether a cell successfully squeezes through constrictions. This project will develop theoretical models whose predictions, once tested, will determine the physical roles of the nucleus in cell migration. From a physics perspective the cell cytoskeleton can be described as a soft gel-like material that is "active" or "out of equilibrium" meaning it is consuming biochemical energy. This type of material has been successfully described by the recently developed theory of "active gels", which has already proved useful in modelling cell movement. Usually in such models the nucleus of the cell is ignored and the cell is treated as a single material, however this project specifically addresses the role of the nucleus. Understanding the mechanical roles of a passive elastic object embedded in an active fluid is a challenging problem within the emerging field of the physics of active (out of equilibrium) matter. Elucidating the physical roles of the nucleus in cell migration will make an important contribution to the grand challenge of understanding the physics of life.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE