- Total grants
- Total funders
- Total recipients
- Earliest award date
- 20 Nov 1998
- Latest award date
- 17 Apr 2020
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer). 16 Sep 2008
To develop effective interventions to improve population health requires a much greater understanding of what works, why, for whom and in what circumstances. This will necessitate the development of epidemiologically and social scientifically Informed complex and multi-factorial interventions that are effective across settings and behaviours; the rigorous evaluation of complex interventions, often using pragmatic controlled trial designs with nested process evaluation and including natural experiments of new policy programmes and the use of routine data to develop and target interventions and to provide sources of data on contexts and long term outcomes for intervention studies. The centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer) brings together team of world class researchers with expertise in a wide variety of quantitative and qualitative evaluation methods and intervention technologies to address these issues. Building on a strong track record, along with partners from public health policy and practice, and the public we will develop, test, evaluate and then implement interventions that are effective in improving the health of the population across settings and behaviours and which address health inequalities, with a particular focus on children and young people. We will also provide high quality training programmes to develop skills of public health researchers
Characterisation of a cortical FoxP1 01 Apr 2016
FoxP1 is a member of the Forkhead family of transcription factors. FoxP1 has been implicated in many developmental processes including aspects of lung and heart and brain development. Specifically, during post-natal stages, FoxP1 is expressed in Satb2+/Ctip2- cortico-cortical projection neurons of layer III-V, and in Tbr1+ cortico-thalamic projection neurons of layer VI. It is known that FoxP1 has a direct genetic link with Autism Spectrum Disorders (ASD) and similar neurodevelopmental disorders causing intellectual impairment, but little is known about its functions in the brain. Therefore the use of animal models to study the role of FoxP1 in ASD and related neurodevelopmental disorders is of importance. The host lab generated a conditional cortical FoxP1 knock-out transgenic mouse model (hGFAP-Cre/FoxP1lox/lox )using a human glial fibrillary acid protein (hGFAP)-Cre line and FoxPl floxed mice. Post mortem immunohistochemistry revealed 80-90% fewer FoxP1-immunopositive cells in the cortex of hGFAP-Cre/FoxP1lox/lox mice compared with wild-type mice. hGFAP-Cre/FoxP1lox/lox mice demonstrated significant hyperactivity, attention deficits and social impairments. Microarray analysis of cortical tissue from hGFAP-Cre/FoxP1lox/lox and wild-type mice has been carried out, so this project aims to validate a list of key up and down regulated candidate genes from the microarray.
The molecular interactions that govern T-cell activation: T-cells recognise foreign antigens in the form of short peptides presented at the cell surface in complex with major histocompatibility complex molecules (pMHC). pMHCs are recognised by the highly variable membrane bound T-cell receptor (TCR). There are two main subsets of T-cells; CD8+ cytotoxic T lymphocytes (CTLs) that recognize pMHC class I (pMHCI) and play a key role in directly killing tumour cells and cells infected with pathogens , and CD4+ T helper cells (Th-cells) that recognize pMHC class II (pMHCII) and play a key role in orchestrating immune responses. Research Goals: 1: Use bacterially expressed soluble pMHCII molecules to investigate the structural and biophysical rules that govern CD4+ T helper cell responses. 2: Develop enhanced peptide ligands to artificially increase the affinity of the TCR/pMHCII interaction. 3: Engineer enhanced pMHCII multimers for the enumeration and isolation of CD4+ T helper cell s. 4: Establish whether modified peptide ligands, that increase the affinity of the TCR/pMHCII interaction, can be used to develop improved peptide vaccines for treating human diseases. Understanding the molecular parameters that govern CD4+ T helper cell immunity is essential for developing therapies and diagnostics for a number of important human diseases.
This proposal employs high-resolution modifications of several elegant techniques to examine whether CD57+ memory T-cells are truly senescent. The techniques employed include in vivo stable isotope labelling of human subjects with deuterated water, state-of-the-art multiparameter flow cytometric sorting, and T-cell clonotyping. Recent refinements to these techniques now allow reliable measurements from very low numbers of cells. Therefore, it is now possible to take full advantage of the power o f multiparameter, multidirectional fluorescence-activated cell sorting to simultaneously measure the kinetics of multiple, even rare, subpopulations of cells, including memory CD57+ CD8+ T-cells that are infrequent in healthy subjects. The key goal of this proposal is to reveal whether CD57+ CD8+ T-cells as well as antigen-specific CD57+ CD8+ T-cells accumulate in chronic infections because of increased proliferation or because of phenotypic conversion from a precursor memory T-cell subset. This information will help to illuminate the ontogeny and significance of memory CD57+ CD8+ T-cells and determine the impact of specific antigen-driven processes in the generation and maintenance of this enigmatic memory T-cell subset.
Why are the hippocampal projections to the mammillary bodies and to the anterior thalamic nuclei vital for normal memory? Anatomical analyses now reveal that these two sets of direct hippocampal projections only arise from two adjacent cell groups in the subiculum, yet the mammillary bodies also project very densely upon the anterior thalamic nuclei (forming a major, indirect route from the hippocampus to the anterior thalamic nuclei). The functional significance of having two populations of subicular cells supporting the same memory system remains unknown.Anatomical tracing techniques will determine whether the two different populations of subicular cells (subiculum ? mammillary bodies, subiculum ? anterior thalamus) receive their inputs from separate sources. Immunohistochemical methods will determine if these two populations of subicular cells are differentially activated by selected learning tasks. Electrophysiological stimulation/recording studies will test whether the direct and indirect pathways to the anterior thalamic nuclei converge onto the same thalamic cells. Attention will also focus on the types of anterior thalamic/mammillary body plasticity that can be driven by subicular stimulation. The results will shape and refine hypotheses concerning the ways in which hippocampal - diencephalic pathways support memory.
Student elective prize for Jemima Tagal. 18 Apr 2007
Factors affecting treatment compliance in patients with spinal tuberculosis - demographics, clinical features and treatment regimens Patient compliance with treatment is a major factor in determining a successful outcome, especially in patients with tuberculosis (TB). Non-compliance results in treatment failure, disease relapse, and drug resistance. Malaysia has adopted the WHO Directly Observed Treatment, Short Course (DOTS) programme in an effort to reduce the national TB incidence. Despite this, local compliance with treatment remains a problem. Spinal TB is quite common in Malaysia, and has an extremely high morbidity. The local demographical, clinical and treatment regimen factors that may affect compliance with anti-TB treatment in Malaysia has not been analysed in patients with spinal TB. Aims of project: Consider the local demographics of patients with tuberculosis of the spine Compare the demographical and clinical features, and treatment regimens of compliant and non-compliant patients with tuberculosis of the spine The ultimate aim of this study is to identify patients at higher risk of defaulting anti-TB treatment to serve as a basis for planning health promotive interventions.
ADHD is a common, impairing neurodevelopmental disorder associated with poor outcomes. It is frequently comorbid with depression, which develops after the onset of ADHD. Identifying children with ADHD at risk of later depression provides opportunity for early intervention. Children with ADHD and chronic irritability are a potential at risk group. In population studies irritability has been shown to predict depression, and a genetic relationship between irritability and depression has been found. Although irritability is a common feature of ADHD, its contribution to depression is yet to be fully explored within an ADHD population. The key aims of this proposal are to test whether children with ADHD and chronic irritability represent a subgroup at increased risk of later depression, and whether presence of chronic irritability in ADHD indexes higher genetic loading for depression. These aims will be addressed using a large clinical ADHD sample. Comparisons will be made between children with and without chronic irritability in terms of later depression, family history of depression and molecular genetic loading for depression. Findings will be expanded upon using a longitudinal population sample, to establish whether irritability cuts across diagnostic boundaries increasing risk of depression in a broad group of child neurodevelopmental disorders.
CD59 as a modulator of T cell activity in vivo. 09 Feb 2006
Identification of molecules that influence T cell activation either positively or negatively will facilitate manipulation of T cell responses in order to amplify those that are beneficial and to inhibit those that are harmful. Preliminary experiments indicate that a complement regulator protein, CD59, downmodulates T cell activity in mice. Mice lacking CD59 show enhanced antiviral CD4+ T cell responses and an enhanced ability to clear virus infections. These studies have led us to hypothesise that lack of CD59 expression on T cells 1) exacerbates virus-induced immunopathology and 2) promotes anti-tumour immunity. The first hypothesis will be tested by comparing virus-specific immune responses and pathology in influenza-infected CD59-deficient and CD59-sufficient mice. In a separate set of experiments we will address whether CD59 expression on T cells limits their anti-tumour potential. Using tumour models already established within the laboratory, we will address whether a) CD59-deficient T cells are more effective than CD59-sufficient T cells at tumour rejection and b) whether silencing of CD59 using siRNA technology enhances the anti-tumour capacity of T cells isolated from CD59-sufficient mice. Lastly, a phenotypic and functional analysis of CD59 expression in human T cell activities in vitro will be undertaken.
LIPID MAPS Resource and Database 16 Jun 2016
LIPID Metabolites And Pathways Strategy (LIPID MAPS) is a resource and database created in 2003 via a 10-yr "glue-grant" from National Institute of General Medical Sciences (NIH) to identify and quantitate all of the major - and many minor - lipids in mammalian cells using a systems biology approach, as well as advance the emerging field of lipidomics. This was accomplished by generating numerous experimental approaches to define the "lipidome" in human and mouse tissues and by developing and maintaining a website which now acts as the global portal for nomenclature, databases, tools, protocols, standards, tutorials, meetings, publications and other resources for the international lipid research community ("Lipidomics GateWay", http://www.lipidmaps.org). Its importance to the field was recently highlighted in Science (https://www.sciencemag.org/content/347/6223/788.short). The "glue-grant" was followed by a legacy grant (expire in July 2016) covering only maintenance of the website, databases and tools. Given the extremely challenging US funding environment, no further options exist locally. This proposal aims to maintain/further develop the resource, and move it to the UK to preserve its internationally recognized classification system and curated lipid structure database, the largest in the world. This will provide essential support for UK and worldwide lipidomics centres.
Unravelling Eve. 13 Oct 2010
A collaboration between artist Joan Molloy, biomedical and social scientists, and women who have experienced postpartum psychosis ("PP"). Molloy will complete a period of residency at the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University in order to develop work that reflects upon issues of motherhood and inheritance- the beautiful complexity of the genetic science mirroring the intricacies of the social, ethical and familial implications of the illness. A 2-day workshop will connect the artist with women who have experienced an episode of PP. Molloy will share her work and lead practical art sessions in order to capture the voice of the women. A gathering of women like this is rare and will give scientists an opportunity for qualitative study so that they can improve their understanding of the emotional aspects of the illness. It will be an invaluable opportunity for the women to establish a dialogue with each other and clinicians, to share their stories and highlight the differences in their care. The artist's intention is to create a body of work, including an arresting film, which encapsulates the science and values the personal histories whilst engaging the public via exhibitions in Cardiff and Christies, London, as well as being available on the web.
In Vitro Meat (IVM) technology involves the culturing of animal stem cells under laboratory conditions into muscle tissue for human consumption as food. Today there are IVM research centers in the Netherlands, Sweden, Norway and the US. Over the last year I have conducted a set of pilot interviews with scientists and activists involved with the technology. This proposed research will allow me to conduct further interviews to produce a complete qualitative data-set of actor's accounts of the technical, social and ethical aspects of IVM. This will allow me - from a Science and Technology Studies perspective - to provide an empirically informed analysis of the social construction of a marginal and unusual biotechnological innovation. I will focus upon how a shared imaginary of the promise of IVM is produced, how this is used to frame the positive and negative ethical aspects of the technology, and how these shape the laboratory work. With existing funds I will spend two months in the Netherlands working with the group there and attend the second international meeting of IVM researchers in Sweden. The requested funds will cover transcription of face-to-face and telephone interviews.
Sense of agency describes our experience of self-control over our actions and resulting outcomes in the world. It can be measured at a perceptual level using causal binding paradigms. Causal binding refers to subjective shifts in perception whereby outcomes resulting from our own actions are perceived earlier in time relative to outcomes preceded by an external signal. Binding is thought to be intrinsically connected to our implicit sense of agency: by perceiving our actions and outcomes more closely linked, this increases our perception of control over the outcome. Strikingly, binding is attenuated in adults when the outcome is negative. This suggests that self-serving biases - the tendency to attribute positive outcomes to the self and negative outcomes to external factors – can influence our implicit sense of agency. We will study for the first time whether self-serving biases also affect children’s implicit sense of agency. We will test: 1) whether self-serving biases operate at a perceptual level in children through causal binding. If they did, this would indicate that self-serving biases operate implicitly. 2) Whether self-serving biases are stronger in children compared to adults. If they were, it would give us insight into the adaptive function of self-serving biases.