NIHRDataInsights/HRCSData huggingface dataset:
Title: Interdisciplinary Training Programme for Clinicians in Translational Medicine and Therapeutics at the University of Cambridge: Support for the 2013 Academic Foundation Year appointments.
Funder: Wellcome Trust

Abstract: We propose an innovative training scheme for Translational Medicine and Therapeutics (TMAT) which builds on the exceptional conjunction on the Cambridge campus of leading scientists and clinical specialists, with an industrial research environment embraced both by international pharmaceutical and local biotech companies. Much of this is found under the same roof, the Addenbrookes Centre for Clinical Investigation (ACCI), with a track record of integrated training: academic with industrial, clinical with scientific, pharmacology & therapeutics with patient-based specialties. The novel TMAT programme will attract the brightest candidates at several levels of seniority, ranging from MB PhD students to clinical lecturers, some wishing translational skills in their chosen specialty, others not yet differentiated who may become future leaders and teachers of TMAT. Each trainee will have a customised programme. Part of this will be a bespoke, modular MSc modelled on the well-known small-group lectures and supervisions of the Cambridge final year undergraduate courses. However the centrepiece for most candidates will be a PhD including formal teaching in a wide range of translational and pharmacological skills, and a project which takes proof-of-concept studies in cell or animal systems forward to proof-of-concept studies in humans. We have assembled an outstanding faculty of PhD supervisors spanning a wide choice of skills and experience in basic and clinical science. All trainees will have the opportunity for hands-on exposure to the design and conduct of experimental medicine studies investigating the therapeutic potential of new drugs, in collaboration with our industrial partner, GlaxoSmithKline (GSK). Our product will be a new generation of clinician scientists with 360-degree vision of the complex landscape of modern therapeutic medicine, who can rise to the challenges and opportunities of 21st century drug development.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: The Centre for the Study of Incentives in Health.
Funder: Wellcome Trust

Abstract: Financial incentive schemes may be more effective than existing approaches in achieving the behaviour change needed for smoking cessation and weight loss. Yet such schemes elicit strong opposition in the media and among the general public, being variously described as unfair , a reward for bad behaviour , and coercive and manipulative . We aim to describewhich characteristics of incentive schemes make them more or less acceptable to the general population, as well as explore the motivations behind judgements of acceptability, such as concern for negative consequences, protected values, judgements of responsibility, and emotions such as disgust or anger. We further aim to disentangle factors which we hypothesize to influence the perception that incentives can sometimes be coercive or manipulative, and to establish the relationship between these judgements and those of acceptability.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: GENERIC HEALTH RELEVANCE
Title: The ethics of translational research: from 'unnatural entities' to experimental treatments.
Funder: Wellcome Trust

Abstract: The UK has one of the most tightly regulated but liberal frameworks for human embryonic stem cell (hESC) research, with the government strongly promoting it as a global centre for translational research. However, the variety of sources of stem cells and the patient-driven urgency for treatments have created numerous ethical issues in this morally contested field. This proposal focuses on key developments in hESC research and neuroscience as critical instances of the translational interface between research and treatment, between scienceand medicine, including the use of inter-species embryos; boundaries/overlaps between experimental research/treatment; and non human primate research for neurological treatments. The central ethical question is the acceptability of changing what it means to be human and/or a person, but others include the impact on human/animal rights; the interests of future generations; the interpretation of safety and risk; the relationship between personal beliefs and professional demands/responsibilities; the place of values in patient choice; the shifts inmoral landscapes as research progresses. The programme expands an established, interdisciplinary team who have an outstanding track record of working and publishing together on ethical issues relating to new medical technologies. It builds capacity and adds value in three interlinking domains, by providing research training/academic career development; developing innovative methodological approaches combining normative and empirical ethics; and undertaking substantive work on the ethics of translational research.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE
Title: Ethics, policy and regulation of human embryonic stem cell research in Iran.
Funder: Wellcome Trust

Abstract: National governance of hESC work and regulation, including ethical, social andlegal debates, is being increasingly influenced by international policies. As these national policies have been both shaped and scrutinized by international mechanisms, researchers at home and abroad have had to adjust their research plans. As hESC research has become an increasingly internationally competitive enterprise for many developing countries including Iran, understanding the ethical challenges presented by hESC science is critically important if we are to solve the problems of adapting to the plurality of beliefs in international policy. Few studies have been conducted on the status of hESC science in Iran. The goals of my project are to map the ethical and regulatory situation of Iranian hESC research and to identify and explore the key factors which have, and are guiding approval and governance ofthe use of HOM/BME STUDENTSHIP 01/07 APPLICATION FOR A DOCTORAL STUDENTSHIP Administration 26 hESCs. Data will be collected from documentary and internet sources; from ethnographic fieldwork at the Royan Institute, the leading hESC centre in Iran; and interviews with key Iranian stakeholders. As the policy implications of the research emerge, they will be refined and widely disseminated through the project's Advisory Group, workshops and the internet,both in Iran and more widely.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE
Title: Influences on psychosocial and physical health in early adulthood: phenotypic enrichment of the ALSPAC cohort through linkage to primary care electronic patient records and other databases.
Funder: Wellcome Trust

Abstract: Since the early 1990s around 14000 young people, from the southwest of England, have been taking part in ALSPAC , one of the largest studies on health and development in the world. They have regularly completed postal questionnaires and attended clinics to assess their health and development and measure things that may influence these. This has been expensive, and is becoming increasingly difficult as the group move into adulthood. For the full value of ALSPAC to be obtained, other means of kee ping in touch and continuing to record the necessary information on the lives of study members are needed. This project concerns one solution to this problem, using routinely collected records to gather the kinds of information previously collected through questionnaires and clinics. These records include those of the NHS and other organisations and government departments. After contacting study-members to seek their permission we will develop ways to collect information on their lives and healt h from various routine sources. We will use this information to answer important questions about the causes of health and social problems amongst young adults today. The lessons we learn will be valuable not just for ALSPAC but for other scientific studies facing similar challenges.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: GENERIC HEALTH RELEVANCE
Title: Chemogenomics.
Funder: Wellcome Trust

Abstract: Knowledge of the human genome sequence promised new therapeutics, yet progress has been slower than expected. One of the challenges for academic researchers, keen to work in drug discovery, has been limited access to pharmacological data describing the interactions between proteins (targets) and small molecules (drugs). These data lie at the heart of translating the new genomic information into new drugs in the clinic. To date such data have only been available piecemeal in the literature or com mercially and this has inhibited the engagement of academic laboratories in effective drug discovery. This proposal requests funds to purchase these data from the company Galapagos in a well-curated and structured format and thus to establish rapidly a world class data resource at the EBI, providing for the first time open access to target-ligand data to facilitate translational research. This proposal is timely, aligning well with the current trend in the pharmaceutical industry to outsource or partner the earlier stages of the drug discovery process. Such data will empower academia to participate in the first stages of drug discovery for all diseases, including neglected third-world diseases, and in the future improved prediction of side-effects.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES;5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: GENERIC HEALTH RELEVANCE
Title: Mechanisms of adhesion to the extracellular matrix.
Funder: Wellcome Trust

Abstract: The shape of our body is created by the shape and organisation of the underlying building blocks, the cells. Our reseach will examine how cells are bolted together, and how the bolts help shape cells and organise them into groups that function together. This proposal focuses on certain bolts, or cell junctions, that stick cells to the extracellular matrix, a meshwork of proteins formed outside cells. These junctions are essential for tissue assembly, and even a partial defect in them causes a skin blistering disease in humans. We seek to understand the workings of the junctions, especially as they are stable structures that hold tissues together, yet the molecules within them are exchanging. This is as if all the bricks of a house were taken out and replaced everyday, yet the house could remain habitable; how does this occur? We will examine how the junctions are turned on from within the cell, and how this controls where and when the bolts are formed. Finally, we will compare and contrast the junctions on the top and bottom of the cell, which are made differently, to discover what key properties of the component parts are needed to make a good junction.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Pre-competitive development of chemical probes for epigenetic targets: a novel paradigm.
Funder: Wellcome Trust

Abstract: Epigenetics is a science which tries to understand, when, how much and what form of a protein is made. The timing, amount and type of protein made, is altered in diseases. For example, in tumour cells, specific proteins are often present at much higher levels than in normal cells. By understanding how these parameters are controlled, we believe we can better understand the factors that lead to many common diseases, such as cancer, diabetes, obesity and Alzheimers Disease. The term chemical probe describes a chemical compound which can modulate (stimulate or block) the activity of a protein, such that it can be used to understand the role of this protein in biology. These probes need to be highly selective for their target protein, and suitable for use in cellular or whole body settings. Some probes may be a starting point for drug discovery. We will develop 25 chemical probes focussing on three important classes of epigenetic proteins demethylases, Bromo and Tudor domains. In this research program, we are building on existing partnerships between successful industrial and academic laboratories. We will make the probes freely available to the general research community, including both academic and pharmaceutical researchers.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Performance bias in behaviour change trials: what is the problem and how should it be studied?
Funder: Wellcome Trust

Abstract: Studies investigating health and behaviour depend upon the co-operation of their participants. Studies of attempts to influence behaviour need to be undertaken particularly carefully. Participants may prefer particular outcomes which can interfere with study findings. They may be more likely to change certain behaviours in the context of a research study that they would not consider changing, or change successfully, outside a research study. They may also change their behaviour as a consequenc e of what exactly is required of them by the research study procedures. This project will summarise what is known about this subject, and develop a framework for better understanding these issues that builds consensus between scientists from different disciplines, and working on different behaviours. It will explore the views of research participants themselves on these issues. Ethical aspects of not providing full information on the study before the decision to participate is made will also be considered. The project will study whether university students whose alcohol consumption is under study, change their behaviour simply by being told they are in intervention or control groups. This work will help find out how big a problem this is, and how it should be approached in future studies.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES);8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE
Title: Functional organization, regulation and cellular roles of elongation factor (eEF) 2 kinase.
Funder: Wellcome Trust

Abstract: This proposal concerns the regulation of protein synthesis, a crucial process in all living cells. Protein synthesis is essential for cells to survive, grow and divide, and to allow cells to express their genetic information. Protein synthesis is tightly controlled, and consumes a great deal of energy and nutrients, the building-blocks of proteins. One way of regulating protein synthesis is through a cellular component called eEF2. In turn, eEF2 itself is controlled by a very unusual enzyme termed eEF2K (an alpha-kinase). This proposal builds directly upon extensive earlier work in the Proud laboratory and a strong collaboration with the Werner group. We aim, first, to investigate how hormones and nutrients control eEF2K and eEF2. This will provide important new information on the control of cell functions. Secondly, this proposal will establish the importance of the control of eEF2 for the regulation of protein synthesis in animal and their tissues. This will aid in under standing the mechanisms that regulate cell growth and cellular responses to nutrients, hormones and stresses. Thirdly, we will study the molecular architecture of eEF2K, to help explain its function and its control. This work will provide substantial new information on the family of unusual alpha-kinases.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Investigation of the nuclear reprogramming process using defined factors.
Funder: Wellcome Trust

Abstract: Understanding the biology of nuclear reprogramming, which is the conversion of adult cells back into an embryonic stem cell state, is a fundamental question in biology with huge potential for regenerative medicine. Recent advances in the field have started to identify genes involved in this process. I previously identified Nanog as a reprogramming factor (1). Subsequently, reverting cells such as from brain or skin (somatic cells) to a pluripotent stem (iPS) cell state - a state in which cells h ave the potential to generate all the cell types in the body - was achieved by expression of defined factors (2, 3). The latter work was the first demonstration that pluripotent-like cells can be directly derived from somatic cells, eliminating the requirement for nuclear transfer/cloning. Despite recent advances, much is still unknown regarding the basic biology of nuclear reprogramming. Following up on my work and that of others I am aiming to improve understanding of the nuclear reprogramming process and thereby enhance our ability to manipulate somatic cells back into pluripotency. This knowledge could then be used to take us a step closer to the generation of customized human ES cells for applications in disease modelling and regenerative medicine.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Intracellular functions of myosin VI in health and disease.
Funder: Wellcome Trust

Abstract: Transport is a fundamental part of life at every level. From the daily journey to work right down to the movement of membrane vesicles in each cell, we have adapted specialised modes of transport to help us function as efficiently as possible. In cells specialised cargo is moved between different locations first along actin filaments and then along microtubule tracks using a variety of motor proteins. The motor proteins that move on actin filaments are the myosins. Since myosin VI is the only m yosin that moves towards the minus ends of actin filaments it must have unique roles in transporting cargo around the cell. So we will investigate how myosin VI is involved in taking up cargo proteins at the plasma membrane, how it moves them into the cell and how they get to their final location. Similarly we will see how myosin VI is involved in transporting newly synthesised proteins to specific regions in the cell or to the plasma membrane for export. In this way we hope to understand the ro le(s) of myosin VI in human disorders such as deafness and cancer and how in the future we may be able to develop potential therapeutic remedies.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: GENERIC HEALTH RELEVANCE
Title: Building a sustainable capacity in dual - use bioethics.
Funder: Wellcome Trust

Abstract: The threat that the modern benignly-intended life sciences revolution could beused for malign purposes is demonstrated by recent incidents of bioterrorism but more particularly by the series of large scale offensive biological warfare programmes carried out by major states such as Japan, the USA, the USSR and the UK in the last century. As capabilities for such misuse have simplified and spread around the world policy-makers in many countries have sought effective policies to deal with the "dual-use" dilemma. Unfortunately, to date the expertise of life scientists and bioethicists has not been applied effectively to assist in thislong-term process of policy development. This proposal aims to build a sustainable capacity to assist that objective both by facilitating analysis of the dual-use bioethics problem now and by training young scholars to continue such work in the future.


Research activity codes: 8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: GENERIC HEALTH RELEVANCE
Title: Analysis of genome maintenance pathways by live cell imaging.
Funder: Wellcome Trust

Abstract: Advances in cell biology rely on more and more sophisticated microscopes to observe the incredibly small structures that comprise a cell. We are a group of cell biologists interested in how cells maintain their genetic material. This is important because changes in the genes can cause a variety of inheritable genetic diseases as well as cancer. Within the cell, different factors and structures are constantly changing place. For example, if genes are damaged repair factors rapidly accumulate at t he sites of damage, and dissolve again once their job is done. A major technique that we are using is to look at cells that have been fixated on glass slides under the microscope. The problem with this method is that the cells are dead when we look at them. To study the dynamics of cellular processes, we need to perform our observations in living cells. Such experiments require sophisticated and specially designed microscopes to avoid damaging the cells during the observation. In this grant prop osal five groups of our Centre are describing their requirements for such a live cell imaging tool in their various research projects; acquiring this equipment would be of great benefit for our research on genome stability.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Using health record linkage in the UK Millennium Cohort Study to investigate childhood obesity, asthma, infections and immunisations in early life.
Funder: Wellcome Trust

Abstract: UK birth cohort studies have made important contributions to understanding of disease and health across the life course. The UK Millennium Cohort Study was set up to understand the social, economic and health-related circumstances of British children born in the new century. It includes children from disadvantaged social circumstances, ethnic minorities and living in all four UK countries. We plan to add to the information already collected on these children in surveys at ages 8 months, 3, 5 and 7 years by linking to their general practitioner and hospital records from birth to 7 years. This will help us answer important questions about children s health. These include questions relevant to obesity and overweight in preschool aged children; infections in early life and childhood asthma and allergic disorders; illnesses due to chickenpox, a vaccine-preventable infection; and childhood injuries. A second goal is to compare survey data with health records to understand more about the qual ity, completeness and consistency of child health data in general practitioner and hospital health records on immunisations, child ethnic group and a range of common childhood conditions.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: GENERIC HEALTH RELEVANCE
Title: Development of statistical methodology for detection and characterisation of genetic factors in complex disease.
Funder: Wellcome Trust

Abstract: The aim of this project is to invent new statistical methods (and to extend existing methods) to allow us to analyse the data generated in genetic studies of complex diseases. We will use advanced statistical techniques to try to find improved ways of answering the questions that genetic studies have been set up to address. We will publish details of the methodology we develop in reputable, peer-reviewed scientific journals and, where appropriate, we will produce and distribute computer softwar e implementing the methods. This will allow other researchers to make use of the methods that we develop in their own studies.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE