NIHRDataInsights/HRCSData huggingface dataset:
Title: Next Generation Components and Systems for Biomedical Imaging
Funder: Engineering and Physical Sciences Research Council

Abstract: Optical coherence tomography (OCT) is a new optical bio-imaging tool which is firmly established in ophthalmology and rapidly emerging in areas such as cancer detection, wound monitoring, cardiovascular medicine and tissue engineering. The performance of OCT depends critically on the performance of the light source and the technique's penetration into the wider medical arena is being delayed by the current generation of sources. Our partnership brings together a multidisciplinary team with demonstrated expertise in the entire OCT development chain from photonic device technologists, through biomedical optics researchers, commercial OCT systems manufacturers and clinical end-users into a co-ordinated programme to address this bottleneck. We aim to develop a new generation of light sources which will achieve not only a price/performance breakthrough but also enable much greater system miniaturisation and ruggedness. The new light sources will be evaluated in an active OCT research laboratory and also offered for evaluation by our commercial partners. Next generation OCT imaging systems will be realised by developing optical components and laser systems which will redefine the state-of-the-art with regard to factors such as output power, emission band-width, tuneability of linewidth, sweep speed, and incorporate design features to simplify the OCT system and reduce cost. The research is vertically integrated from the development of new epitaxial techniques, modification of semiconductor materials, device design and fabrication technologies, development of swept laser systems, and their assessment and implementation in OCT systems studying real biological samples.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Innovation and Knowledge Centre Regenerative Therapies and Devices Tranche 1 IKC RTD
Funder: Biotechnology and Biological Sciences Research Council

Abstract: The Innovation and Knowledge Centre in Regenerative Therapies and Devices will provide a sustainable platform to address the creation of new technologies in Regenerative Therapies and Devices. It will promote their accelerated adoption, with increased reliability, within a complex global marketplace with increasing cost constraints. Therapies and devices which facilitate the regeneration of body tissues offer the potential to revolutionise healthcare and be a catalyst for economic growth, creating a new business sector within healthcare technology. The IKC RTD will build upon the culture and research landscape of the University and its partners (industry, NHS and intermediaries/users) through the development of new innovation infrastructure and practices which deliver major clinical, health and industry outcomes.In the first year of operation the IKC has:1. Recruited and established a core innovation team to manage and grow the activities of the IKC.2. Established academic supply chain, new centre with 160 researchers.3. Won 50m new research income, funding over 120 research projects.4. Defined a new strategic framework for innovation.5. Established an innovation pipeline with stage gates and criteria for progression.6. Defined and developed the IP portfolio through definition of the unique capabilities.7. Established a pipeline of 63 collaborative innovation projects.8. Engaged with 26 different companies in collaborative innovation projects.9. Established a wider network of 80 plus companies.10. Contributed to nine new products that have reached the market.11. Defined a model for sustainability of IKC RTD.12. Received significant national and global recognition through political visits and extensive media coverage for research and innovation.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: Therapeutic Imaging
Funder: Engineering and Physical Sciences Research Council

Abstract: In the majority of current medical practice, diagnostic imaging and therapeutic procedures are intrinsically separate, often involving entirely different teams of experts. Whilst this takes advantage of the highly developed skills of narrow specialisms, it can have significant drawbacks: it is resource intensive; lack of real-time monitoring increases the risk of ineffective treatment or collateral damage; long waiting times between diagnosis and treatment and/or treatment and follow up are psychologically and often physically detrimental to patients due to disease progression; and there is increased risk of patients not attending or not complying with treatment regimes. The aim of the proposed research programme is to build a world leading multi-disciplinary team to develop new methods and technologies that will truly integrate diagnostic and therapeutic procedures and produce a step change in clinical practice. The research activity will be focused in three areas:-Developing new types of agent for targeted drug delivery which will enable clinicians to monitor the placement, transport and controlled release of drugs and other therapeutic material. -Understanding the mechanisms by which these agents interact with cells and tissue to enable the design of safer, more reliable delivery strategies-Designing technology that will not only enable tracking of therapeutic material but also active manipulation and stimulation.The outcomes of the research will directly benefit patients, clinicians and other healthcare workers by providing new, more efficient and effective procedures. This will in turn yield economic benefits, directly through new products and services for the biomedical and pharmaceutical industries, and by reducing demand on healthcare resources. To realise these outcomes, a key feature of the research strategy will be to maintain close working relationships with both clinical and industrial partners to maintain the focus of the work on the most relevant research challenges and to identify and access the most appropriate and efficient routes for translation.The research will also lead to new discoveries and the development of a range of experimental and theoretical tools which will be of direct benefit to the research community. Another important aspect of the programme will thus be training of the research team to communicate effectively across disciplinary boundaries as well as through wider public engagement activities. Through building on the proposed pilot studies and collaborations with academics, clinicians and industry a research project portfolio will be constructed which will sustain the activity of the group beyond 5 years in order to fully realise the integration of diagnostic imaging and therapy from concept to clinic.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;5.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE
Title: Control Engineering Inspired Design Tools for Synthetic Biology
Funder: Engineering and Physical Sciences Research Council

Abstract: Recent technological advances allow us to manipulate the circuitry inside cells and to modify their behaviour. Moreover, we can now design entirely new circuits within cells. This ability parallels the technological advances in Electrical Engineering in the mid-20th century and the potential of this new technology is being recognised throughout the world. This new field, which goes under the name of Synthetic Biology , has been described as the Engineering of Biology .This field is in its infancy and inevitably faces several challenges. For example, current practice concentrates on the design of very simple circuits by putting together several components/parts that are believed to be characterised adequately. When implemented, these circuits almost never work as expected not least because of the uncertainties/noise that are present inside cells, the level of cross-talk with other circuits inside cells as well as the limitations posed by measurement and implementation technologies. In fact the design/redesign process is still more of an art rather a technology, in that it is mainly based on intuition and moreover, uncertainties/noise and crosstalk are not taken into account at the design stage. For Synthetic Biology to fulfil its potential and be able to produce large-scale biocircuits with richer functionality, the design cycle needs to take into consideration all available biological 'knobs' that could be used to tune the circuit's behaviour, as well as the uncertainties of the environment in which these circuits will need to function.In this project we propose a systematic design approach that uses engineering principles for the analysis and design of biological networks. The objective is to develop a new design cycle, inspired from control engineering practice but adapted to the constraints and needs of synthetic biology for the design of biosystems that behave in a predictable fashion. This engineering cycle will be exemplified on three systems of fundamental importance, i.e., oscillators, filters and switches with the goal of optimising their performance in such a way that they work reliably within uncertain environments. This research will be undertaken at Engineering and Life sciences departments in the three institutions involved in this research (the University of Oxford, the University of Cambridge and Imperial College London) and will be supported externally with international project partners who will collaborate on this project (California Institute of Technology (CalTech), Eidgenossische Technische Hochschule (ETH) Zurich, and the Massachusetts Institute of Technology (MIT)).


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Alignment of Synthesis, Medicinal Chemistry and Structural Genomics to Accelerate UK Drug Discovery: Network SMS-Drug
Funder: Engineering and Physical Sciences Research Council

Abstract: This programme will establish an Academia-Users Network in Chemical Biology to initiate, establish and nurture collaborative projects for the advancement of the drug discovery process. It aims to expand the capability of UK drug discovery, with new drug targets, new tools to validate targets and new multidisciplinary partnerships to explore the platforms, tools and targets of the future. In the post-genomic age opportunities for the development of new clinically validated targets for drug discovery and ultimately medicines are considerable. Drug discovery resources in academia and industry are not used efficiently, to the detriment of industry and society. Duplication could be reduced, and productivity could be increased, by performing basic biology and clinical proofs of concept within open access industry-academia partnerships. The major obstacle to clinical validation of new drug targets and the invention of new medicines is the availability and efficient delivery of small-molecules probes in order to understand the basic biology. Provision of these probes will allow for pre-clinical validation of drug targets and reduce the duplication of efforts across the pharmaceutical industry. Failures of potential drug molecules in late stage clinical trials result in enormous cost to the companies involved, the pharmaceutical industry in general and also dashes the hopes of countless patients. A relatively poor understanding of disease mechanisms, particularly in humans, confounds the drug discovery process and represents a pivotal area of biological research. Potent, selective and cell-permeable chemical probes are valued reagents in both fundamental and applied biological research, and they are essential for preclinical target validation in academic and industrial laboratories. Strategic alignment of academic synthetic chemists, molecular modellers and structural biologists with industrial end users will provide a blueprint for the provision of open access chemical probes to support clinical validation and drug discovery efforts within the UK.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: GENERIC HEALTH RELEVANCE
Title: Changing the Synthesis Landscape with Boron at the Helm: from Chiral Organometallics to Assembly Line Synthesis
Funder: Engineering and Physical Sciences Research Council

Abstract: Chemistry is unique amongst the sciences in that it has the power to constantly rejuvenate itself since it has the ability to study what it also creates. Creating molecules is where the developments in chemistry begin, which ultimately leads to the advancements in society. Within this context, the synthesis of organic molecules is central to many research disciplines from medicine to materials. However, despite substantial progress, the problems and difficulties associated with chemical syntheses severely limit the rate of growth and development of these disciplines. These fields are constrained by what chemists can make easily, rather than by the imagination of the scientists. In order to meet the emerging challenges across new disciplinary boundaries in a rapidly changing scientific landscape we require a step-change in the development of more rapid and robust techniques in organic synthesis. Our proposal is to essentially 'grow' a carbon chain with specific substituents attached at specific places and with specific stereochemistry, so that so that at the end of the sequence a complex target molecule which may be a natural product, pharmaceutical or synthetic material will be produced essentially in one step. This is a hugely ambitious goal. The 'growth' phase is conducted using a chiral carbanion with a good leaving group attached (a carbenoid) which reacts with a boronic ester to give a homologated (enlarged) boronic ester. Repeating this reaction, using a different carbanion on the new boronic ester enables a second growth step to take place. The growth steps can be likened to adding lego pieces until a model has been created. Such a process has resonance with the remarkable machinery nature has evolved [polyketide synthases (PKS)] in its biosynthesis of polyketides. Indeed, by variation of the carbenoid and its stereochemistry (lego pieces) a diverse range of molecules with specific shape should be accessible thus enabling rapid structure-activity studies on complex molecules. The boronic ester intermediates are stable organometallic reagents which are easily accessible with control over their shape. We plan to embark on a novel method of activation of these intermediates so that they can be transformed into a much broader range of molecules bearing new functionality. Such novel methodology would significantly expand the landscape of readily available chiral organic molecules. The (desired) properties of a molecule are defined by its shape and functionality. Being able to control these critical features lies at the heart of chemistry and is what drives much of biological and materials chemistry. We aim to create new tools to enable us to easily synthesise a broad array of molecules with control over their shape and functionality. Our proposed synthesis program will provide an additional new tool to enable science.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Metal Catalysed Decarboxylative C-C Bond Formation Reactions
Funder: Engineering and Physical Sciences Research Council

Abstract: Organic synthesis has undeniably made tremendous progress over the past two centuries. Nevertheless, our ability to efficiently synthesise molecules is mostly limited to targets of low structural complexity. Preparing more sophisticated compounds is currently possible; however, their syntheses are highly inefficient: they usually involve a high number of reaction and purification steps, with a consequent increase in waste generation, and a dramatic reduction in overall yields. Consequently, these syntheses are generally not applicable to the sustained production of complex molecules of interest. This observation has led to a general consensus in the scientific community as to the urgent need for new chemical processes supporting the development of a "greener" and more sustainable chemical industry. Traditional synthetic strategies require the presence of reactive functional groups that are used as handles for further functionalisation. This requirement is one of the factors dramatically enhancing the difficulty of syntheses. In addition, often these 'handles' are not part of the final molecule and are lost as waste by-product that may be toxic and needs to be separated and dealt with. The last two decades have seen the emergence of a more straightforward alternative: the direct functionalisation of C-H bonds. Through this strategy the typically inert C-H bonds, ubiquitous in organic molecules, can be activated by transition metal catalysts and subsequently functionalised. A second approach involves the use of carboxylic acids that can be activated via decarboxylation to direct very accurately the reactivity in a given molecule. In our research we want to combine both of these new types of reactivity to develop a series of methodologies that can form bonds between carbon atoms of molecules with a very limited amount of waste by-product and in an efficient manner. The development of such new transformations will impact on all applied areas, such as the synthesis of pharmaceuticals, agrochemicals and new materials, by providing cheap and easy access to molecules that are very difficult to make to date (and therefore not used commercially).


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Cu(II)-Catalysed C-H Activation Routes to Heterocycles; Applications in Target Synthesis
Funder: Engineering and Physical Sciences Research Council

Abstract: Heterocyclic compounds are the mainstay of the pharmaceutical and agrochemical industries. As part of our on-going research programme geared towards the synthesis of heterocyclic systems of medicinal interest, we have placed a great deal of emphasis on designing streamlined and environmentally friendly synthetic procedures. Thus, we have successfully developed a number of improved routes to heterocyclic building blocks utilising cascade and telescoped processes. As part of this programme, we recently developed a high yielding moisture- and air-insensitive procedure for the preparation of 3,3'-disubstituted oxindoles from simple aniline-derived starting materials via a formal double C-H activation approach using an extremely cheap and readily available reagent, cupric acetate monohydrate (ACS grade, < £1/10 g), in DMF as solvent. Such a straightforward method of generating quaternary stereogenic centres is noteworthy. In 2010, we discovered a much improved procedure which uses catalytic amounts of cupric acetate monohydrate in toluene or mesitylene as solvent and gives equally high yields of oxindole products without the need to exclude air and moisture. We are now fully focused on demonstrating the broad utility of the improved cupric acetate monohydrate procedure and we believe that the potential of this methodology is enormous, particularly, given that many of today's drugs are based on oxindoles (e.g. the blockbuster anti-cancer drug, Sutent). The main aims of this proposal are therefore: (i) to further exploit the novel copper-based C-H activation chemistry to develop a route to spirocyclic oxindoles, (ii) to explore the development of asymmetric variants for all substrate classes, (iii) to extend the methodology to the synthesis of related heterocyclic systems, and, very importantly, (iv) to apply, and therefore validate, the new copper-catalysed cyclisation procedure in complex pharmaceutical and natural product target synthesis. It is our aim to dvelop this new procedure into a truly powerful synthetic tool with far-reaching applications in both academic research and industrial medicinal chemistry and scale-up processes. This ambitious programme will be carried out by a PDRA over a 3 year period.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Sustainable Phosphorus Chemistry: Catalytic Asymmetric SN2 Reactions
Funder: Engineering and Physical Sciences Research Council

Abstract: This proposal describes innovative new chemistry that will transform phosphorus-mediated substitution reactions by rendering them catalytic in the phosphorus component and, therefore, devoid of phosphorus waste. This will substantially reduce the economic and environmental footprint of phosphorus-mediated processes that are used by academic and industrial chemists on a daily basis and allow the full commercial potential of the chemistry to be realized. Furthermore, the world's supply of phosphate rock, the material from which most organophosphorus compounds are derived, is running out and the new catalytic reactions represent a sustainable alternative to current methods. Despite over one hundred years of progress many of the transformations that underpin chemical synthesis, e.g SN2 reactions of activated alcohols, are inherently wasteful. Since the 1960s organic chemists have used phosphorus-mediated reactions, such as the Mitsunobu reaction, for the synthesis of important fine chemicals including pharmaceuticals. However, at present, this chemistry generates at least one molecule of phosphorus waste for every molecule of product produced. This impacts heavily on the environmental and economic footprint of the chemistry and for over a decade industry has been asking for a solution to this problem. For example, a recent report authored by process chemists from GlaxoSmithKline, Pfizer, Merck, Lilly, Schering-Plough and AstraZeneca stated that "the ideal Mitsunobu reaction would be catalytic in nature" and, most significantly, "future research towards making this transformation green is required to realize its full potential in commercial applications". To meet these demands new sustainable phosphorus chemistry is urgently required. This adventurous programme, that is aligned with the "Dial-a-Molecule" grand challenge, will deliver highly sought after substitution reactions that are catalytic in phosphorus. This will dramatically reduce downstream waste and open up a range of new applications in pharmaceutical and agrochemical synthesis that will benefit UK industry. Moreover, new fundamental chemistry of phosphine oxides, incorrectly assumed by many to be unreactive compounds, will be explored. Finally, the new strategy described is applicable to many other important phosphorus-mediated reactions and, therefore, forms a new platform for catalysis. This proposal benefits from: (a) exciting preliminary results that indicate the chemistry proposed is deliverable; (b) a collaborative experimental, theoretical and mechanistic approach and (c) the PI's reduced teaching load (as a new academic) allowing him to closely monitor progress and drive the project forward.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE