- Total grants
- Total funders
- Total recipients
- Earliest award date
- 10 Apr 2001
- Latest award date
- 30 Sep 2018
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Designing unconventional peptide modifications to universally enhance CD4+ T-cell activation 28 Nov 2017
The CD4+ T-cell response is of fundamental importance in generating effective immunity to pathogens and cancer. The interaction of the CD4+ T-cell receptor (TCR) with peptide presented by HLA class II heterodimers (pHLA-II) is the central point of the adaptive immune response. Overwhelming evidence suggests the affinity of this interaction dictates the efficacy of T-cell activation (Panhuys et al Immunity 2014), and indeed, the fundamental importance of TCR:pHLA-II affinity was illustrated in a cohort of long term HIV controllers (Benati et al JCI 2016). Crucially, low affinity TCR:pMHC interactions contribute significantly to cancer vaccine failures. The biology of this interaction has been ignored by the vast majority of vaccine studies. This project takes a fundamentally different approach to therapeutic and prophylactic vaccines, by focusing on the details of the TCR:pMHC-II interaction. We aim to utilise our proven ability to generate high affinity TCR:pMHC-II interactions, with no loss of specificity, by targeting changes in the epitope flanking regions. This approach will illustrate how HLA-bespoke vaccines can be generated, and will be tested (using HLA-DR-transgenic mouse) in models of infection and cancer. The long term aim is to match superior vaccines to the individuals' HLA background, personalising treatment, and transforming vaccine design.
Influence of Sleep on Human Brain Structure 08 Nov 2017
Sleep is essential to brain functioning and its loss greatly impairs cognition, yet the brain mechanisms underlying the cognitive benefits of sleep remain largely unclear. During sleep, the brain’s functional networks break down, with different brain regions showing decoupled activities. I hypothesize that this decoupling of brain regions will facilitate the remodeling and optimization of brain structural networks, leading to improved brain functioning and cognitive performances after sleep. I will test my hypothesis in human participants by combining measures of brain structure, function, cognition, with brain stimulation during sleep. First, I will study how the structure of inter-regional connections change after sleep, whether these changes improve the network properties, and how these changes are reflected in the function of inter-regional communications. Then, I will study how the post-sleep changes in brain function correlate with brain activity in sleep, and whether these functional changes can be modulated by brain stimulation during sleep. Last, I will study how the post-sleep changes in brain structure differ across different inter-regional connections, and whether these structural changes can predict the selective influences of sleep on different cognitive performances. Overall, this project aims to explore how sleep benefits cognition by improving brain structure for higher functionality.
Stratification of bipolar disorder: harnessing clinical heterogeneity and genetics shared with other disorders 08 Nov 2017
The bipolar disorder diagnostic category, while clinically useful lacks biological precision/validity. There is consensus that this biological imprecision is impeding aetiological research and the development of new therapeutic interventions. BD overlaps with schizophrenia (SCZ) and Major depressive disorder (MDD) in its clinical presentation. It has a large polygenic component to it genetic aetiology which it partially shared with SCZ and MDD. This suggests the hypothesis that the clinical heterogeneity seen in BD may be due to underlying causal heterogeneity and the degree of clinical similarity between individuals diagnosed with BD, SCZ and MDD reflects overlapping risk alleles which selectively influence specific, shared clinical characteristics, rather than the global risk for the disorders. This study will use genome-wide and pathway-specific polygenic risk score methods to identify biologically valid stratifiers for BD, informed by psychopathological characteristics AND genetic liability. BD may be the extreme phenotypic expression of psychopathological dimensions distributed throughout the general population to explore this further, generalised latent variable modelling will be used to examine and compare the latent structure of the psychopathological phenotypes in BD cases with those found in the general population and LD score regression will test for genetic correlation
Structural and biological characterisation of novel phosphatidylethanolamine lipids generated by 12/15-lipoxygenase in monocytes and macrophages. 11 Jul 2006
12/15-Lipoxygenase (LOX) is a macrophage enzyme whose deficiency protects against atherosclerosis, hypertension and diabetes. Recently it has been proposed to play a role in promoting inflammation resolution. Using liquid chromatography-mass spectrometry (LC/ESI/MS/MS) we have identified 4 novel lipids generated by 12/15-lipoxygenase (LOX) in IL-4-treated human monocytes (m/z 738 - 782), and MS/MS analysis indicates that they comprise 15-hydro(pero)xyeicosatetraenoic acid esterified to various forms of phosphatidylethanolamine (15-HETE-PE). Levels of these products are considerably (4-10-fold) higher than levels of free 15-HETE released, making them the predominant 12/15-LOX lipids generated by human monocytes. Similarly, in murine peritoneal macrophages, considerably higher levels of esterified 12-HETE than free are detected following activation (10-fold). In this project, we will use LC/ESI/MS/MS to fully characterise the structures of these 12/15-LOX products in monocyte/macrophages. Receptor/agonist-dependent signaling pathways leading to their generation will be determined. Finally, their signaling activities will be characterised in vitro using cultured macrophages/monocytes, and in vivo using an established murine peritonitis model. The structural and biological characterisation of these novel lipids will further our knowledge of the roles of 12/15-LOX in inflammation and may provide new therapies for promotion of resolution and wound healing.
Working title: "Boy Genius". 01 Jun 2006
'BOY GENIUS'Boy Genius' is an innovative approach to the exploration of contemporary developments in human genetics related to mental health. This activity encourages an appreciation of different views about this complex area of science and associated social and ethical issues through interactive participation in the story of a young man's experience of mental illness. UWitWithin an exciting and stimulating'installation' drama environment, participants embark on a complex set of investigative tasks, which make demands on their cognitive, emotional and artistic faculties. An initial encounter with anpowerful intriguing and challenging theatre stimulus awakens participants' desire to undertake this demanding journey of learning and understanding. Interpretations and decision-making within the activity are determined by the participants' in-role contributions. The activity is task driven and structured to enable it to be an intellectually and emotionally stimulating approach to learning. A collaboration between the Wales Gene Park and Gwent Theatre, 'Boy Genius' will be offered to schools and colleges for students, aged 16 -18, from science, humanities and art subjects as concepts and skill elements relate to cross-curricular citizenship requirements. Complementary support material will be developed for teachers and tailored for use across different disciplines, both to draw students into the activity and to extend the learning experience beyond the activity itself. The development, delivery and outcomes of the activity will be evaluated to feed into the on-going development of the project and as a final analysis of the success of the activity.
Developmental psychology is an area that has intrigued me for many years. In face it was one of the main reasons to study psychology at degree level. The variety of experiences I have had working with children has encouraged a keen interest in the different ways in which children develop. The majority of my work experience has involved working with atypically-developing children in both school and play settings. I also spent some time in Sri Lanka after the Boxing Day Tsunami, where I volunteered in camps for displaced families, and at an orphanage for children with learning difficulties. All of these experiences have demonstrated the importance of social interactions, and not only biological dispositions, in development. Whilst studying my undergraduate degree at Cardiff university, my interest in developmental psychology was reinforced when I was given a chance to work as a research assistant for the research group headed by Dr. Merideth Gattis. This work allowed me to see the ways in which imitation is a skill which is not only interesting in its own right but helps to uncover other social and cognitive processes as well. Melzoff (1995) presented infants with completed or incompleted actions by humans or machines. When offered the chance to imitate, infants completed the actions which had been performed by human models but not those performed by machines. Therefore the imitation demonstrated that infants replicated intended rather than viewed actions; a result that has been replicated in a number of different studies. This ability to understand psychological processes of others has been suggested to be lacking in children with autism (Aldridge, Stone, Sweeney & Bower, 2000). This idea of individual differences in intention understanding (as measured by imitative response) in different populations is of interest to me due to my work experience with both children with disabilities and a group investigating goal directed imitation. I believe a PhD would allow me to combine aspects of both my undergraduate degree and the extensive experience I have acquired over the past seven years of working with children. Once I have completed my PhD, I hope to continue with research looking at social cognition in both normally and atypically developing populations.
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.
Role of PLC-zeta in generating Ca2+ oscillations and triggering egg activation at fertilization. 09 Nov 2006
At fertilization, a sperm activates the egg by causing a large transient increase in intracellular Ca2+ concentration. Mammalian eggs characteristically exhibit a series of cytosolic Ca2+ oscillations lasting several hours, mediated by elevations in inositol 1,4,5-trisphosphate (InsP3) concentration. However, the molecular mechanism explaining how a sperm induces increased InsP3 in the egg remains unclear. The sperm factor theory proposes that the sperm releases a specific factor into the egg cytoplasm at fertilization, which triggers Ca2+ release and egg activation. We have discovered a novel, sperm-specific phospholipase C isoform, PLC-zeta, (PLCz), and demonstrated that PLCz causes Ca2+ oscillations and activation of mouse eggs indistinguishable from fertilization. These observations are consistent with PLCz as the sperm factor. We aim to establish whether PLCz constitutes the exclusive physiological signal for development at fertilization by studying the phenotype of a PLCz knockout mouse. We also wish to define the subcellular targetting of PLCz within sperm and zygotes, and elucidate how PLCz causes repetitive Ca2+ changes in eggs and other cells. To understand how PLCz enzyme activity is regulated, we will examine the structural and functional contribution of distinct domains to the structure and interactions of this novel signalling protein.
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.
The role of the extracellular calcium sensing receptor (CaSR) in development and plasticity. 01 Jul 2009
1. Investigate a possible role for CaSR in regulating dendritic spine density & morphology in the hippocampus 2. Further characterize the published role of CaSR in regulating gross dendritic morphology in developing neurons  3. Extend preliminary observations suggesting CaSR may have a role in early development of sympathetic neuroblasts and neurons (see Appendix) 4. Participate in studies to elucidate the intracellular signaling pathways by which CaSR promotes axon growth in fetal sympathetic neurons
Understanding cell type specific regulation of gene expression is critical for understanding differentiation in multi-cellular organisms. The male germ-line is a unipotent cell type, committed only to making sperm. During spermatogenesis dramatic changes in gene expression occur, to facilitate the differentiation of highly specialised cells. We have previously identified a group of testis specific transcriptional regulators important for this spermatogenesis specific gene expression in Drosop hila. We will test the TEV protease system for cleavage of target proteins in the Drosophila male germ-line with known factors, and develop a P-element replacement exon tagging approach to allow specific ablation of potentially many target proteins in a controlled manner. We will test this approach by initiating the analysis of testis-specific functions of conserved potential transcriptional regulators that act in both the male germ-line and in other cell types, concentrating on a small set of proteins for which we already have localisation data and functional predictions.
"7th International Congress on Traditional Asian Medicine" to be held in Thimbu, Bhutan on 7-11 September 2009 21 Jul 2009
This panel in the Seventh International Congress on Traditional Asian Medicine (http://www.iastam.org/conferences.htm) will consider medicine and healing in the pre-Buddhist tradition of Tibet, known as Bon. The main medical text of this tradition is known as the Bumzhi (the four hundred thousand healing arts), which according to Bon history dates back more than 1 000 years to the Central Asian kingdom of Zhang Zhung. In the 1930s the Bon lama and scholar Khyungtrul Jigmai Namkai Dorje (1897-1955) wrote a comprehensive four-volume commentary on the 'Bum bzhi, the Khyung sprul sman dpe, which is based on both Buddhist and Bonpo sources. In recent years there has been a resurgence of the Bon medical tradition which is currently been taught in a number of medical schools in Tibet and Nepal using both the 'Bum bzhi and the Khyung sprul sman dpe. The panel consists of 11 participants all presenting on different aspect of this ancient medical tradition. Several of the papers will focus specifically on Khyungtrul's medical work.
The increased incidence of antibiotic resistant bacterial strains such as MRSA and VRSAover the past few years has identified the necessity for development of alternative therapeutic strategies. Professor Nicholas Topley and Dr Simon Jones at the University of Wales have been awarded translational funding to further develop a therapeutic to supplement the body's existing defence system to help clear various types of bacterial infection.
"History of ancient science and medicine vs economic history, Classical Association conference 2010" to be held at Cardiff University on 7-10 April 2010. 15 Feb 2010
The Classical Association's annual conference is the premier annual gathering of classical scholars within Britain, providing a forum for discussion and dissemination of information over a wide spectrum of topics within the discipline as a whole. It attracts large numbers of proposals for papers, and the increasingly international profile of the programme is an indication of the high regard in which it is held. A special feature of the conference is that it brings together academics from all career stages: not only established scholars but also postgraduate students, who will provide the next generation of academics. This allows a unique opportunity to establish international relationships and enhance current research. Since the conference is also well attended by school and college teachers, the international dimension is disseminated through all levels of classical education not only within the UK but also abroad, with consequent benefits to teaching and learning. The proposed session on ancient medicine should help to bring to the attention of a wide constituency the importance of integrating ancient medicine into both the teaching curriculum and the research agenda.
This project examines the history of Japan's traditional medicines since the late 19th century. Kampa, a localised version of traditional Chinese medicine, had been Japan's traditional medicine for over a millennium. Following the Meiji Restoration of 1868, Japan began a rapid programme of Westernisation and modernisation that included Kampa's replacement by Western style medicine. After 1874, only physicians trained in Western style medicine were permitted to practice in Japan. But the type of traditional medicines used in Japan before the Meiji Restoration continued to be consumed. Kampa revived in the decades after World War II. The resurgence of Kampa medicines was due to a combination of factors, including the realisation of limitations to Western medicines following drug tragedies such as the thalidomide; the development of technologies to mass produce standardised versions of Kampa medicines; and the government's 1976 decision to recognise Kampa medicines as legitimate prescription drugs. My research aim is to provide a comprehensive multifactorial explanation for the fall and rise of traditional medicines in modern Japan.
Developmental neurochemistry underlying axonal growth, survival and guidance of midbrain dopaminergic neurons. 15 Jul 2008
(1.) To investigate biochemical mechanisms underlying the growth, development and survival of midbrain dopaminergic neurons with respect to the nigrostriatal pathway (2.) To examine the influence and significance of the TNFRSF and TNFSF in mediating dopaminergic growth (3.) To extrapolate novel findings to clinically relevant models of Parkinson's disease using transplantation studies to functionally reconstruct the nigrostriatal pathway.