- Total grants
- Total funders
- Total recipients
- Earliest award date
- 09 Jun 1998
- Latest award date
- 25 Jan 2019
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Role of mast cell tryptase activation of human airway smooth muscle cells in asthmatic airway inflammation and remodelling. 07 Nov 2005
Recent studies have shown that increased mast cell infiltration of airway smooth muscle (ASM) bundles is an important determinant of the asthmatic phenotype, suggesting that mast cell/ASM interactions may play a critical rolein asthma. The key mast cell mediators which alter ASM function have not been identified but tryptase, an abundant mast cell-specific mediator, is the most likely candidate. Little is known about tryptase's effects on the synthetic properties of ASM cells which are increasingly thought to play an important role in chronic inflammation and remodelling. It is also unknown if ASM responses to tryptase are enhanced in asthma. Here we will test the hypothesesthat tryptase activation of ASM cells plays a key role in asthmatic airway inflammation and remodelling and that asthmatic ASM cells have an enhanced response to tryptase compared to non-asthmatic cells. We will characterise: 1)tryptase-induced ASM cytokine gene expression profile; 2) tryptase-induced ASMcell functional changes (ASM and endothelial cell proliferation and migration,and in vitro angiogenesis) and the roles of individual cytokines in these processes; 3) the molecular mechanisms whereby tryptase acts. Strategies targeting tryptase and its signalling pathways may provide a novel approach toasthma therapy.
Student elective for Edward Prior. 19 Jul 2006
Despite effective therapeutics and detection strategies, the prevalence and incidence of leprosy is still a public health concern across parts of Africa, Asia and South America. There is also much that remains unknown about its transmission and pathophysiology. Importantly it is not yet understood why some people are able to contain the infection and remain healthy whereas others succumb to the disease because they are unable to mount an effective immune response. The host response to this disease ranges along an immunological spectrum. T helper cell type 1 leprosy responses, distinguished by IFNg expressin, result in paucibacillary (tuberculoid) leprosy where bacteria re contained and destroyed. Multibacillary (lepromatous) leprosy is characterised by Th2 cells expressing IL4 which are unstable and can switch from protective to susceptible depending on the immunological status of the host. Leprosy is caused by Mycobacterium leprae. It infects primarily Schwann cells and macrophages. Host responses to infection involve the formation of granulomata, an attempt by the host to contain and destroy the bacteria. Those with tuberculoid leprosy mount an effective cell mediated immune response with T cell activated macrophages killing the bacteria. There is an absence of an effective T cell response in lepromatous granulomata and macrophages are unable to kill their bacterial load. However, in an attempt to control infection there is further macrophage recruitment. It is the role of these fresh cells that my host laboratory are currently investigating as part of their efforts to establish an in vitro granuloma model. Work published by Dr Adams' laboratory has shown, in mice, that activation of freshly recruited macrophages is able to reduce the viability of M. leprae even in the absence of T cells. During my elective period we would like to further investigate the role of human macrophages using an in vitro model.
Pilot study to evaluate whether proactive adjustment of Ventriculoperitoneal shunt valves can maintain larger ventricles and/or decrease shunt failure in children with hydrocephalus The study aims to assess whether pro-active shunt adjustment by surgeons affects the following: The ability to maintain large ventricles (by measuring mean and median ventricle size from CT/MRI scans) The rates of slit ventricles and/or slit ventricle syndrome The rates of shunt failure by assessing Kaplan-Meier life table analysis It is hoped that this study will be the forerunner of a much bigger prospective trial to develop a protocol for shunt valve adjustment.
There has been considerable normative debate about the applicability of international bioethical thinking to medical practice and research in developing countries. Little is known about how this plays out empirically, particularly about the interaction between indigenous and international bioethical thinking. It is also acknowledged that international writing on bioethics has tended to be dominated by Anglophone values and models of research and medical practice, whose universality is contested. This empirical study of the ethics of medical practice in Burkina Faso will: describe how practitioners deal with the potentially competing claims of local and international ethical expectations; examine the influence of a francophone context and its different traditions of ethical analysis. WP1 A literature review covering international bioethics, the sociology of the professions and the anthropological study of indigenous healers; archival work on the institutional foundations of European medicine in Burkina Faso. WP2 The role of international organizations and NGOs in shaping the contemporary organisation of health services in Burkina Faso, particularly the ethical expectations embedded within their interaction with the state. The approach of regulators. WP3 The bioethics of indigenous practice and the standards adopted by local healers in interaction with consumers. WP4 The European-style medical practitioners and the ethical standards that they adopt in interactions with their consumers and their regulators. WPS PhD thesis and journal articles in French and English, together with an accessible web summary of the main findings. WP1 & WP5 will be mainly completed in Nottingham; WP2-4 will be completed in Burkina Faso.
Mechanism of neutrophil elastase induced pulmonary fibrosis: the role of alphavbeta6 integrin mediated TGFbeta activation. 08 Jul 2008
Idiopathic pulmonary fibrosis is characterised by excessive matrix deposition within the lungs. We have recently shown that neutrophil elastase null (ne-/-) mice are protected from bleomycin induced matrix depostion due to a failure to activate TGFbeta. NE can proteolytically cleave TGFbeta from extracellular matrix in vitro, but whether this leads to active TGFbeta in vivo is unknown. We have data demonstrating that NE can also initiate intracellular signalling pathways that activate TGFbeta, v ia the TLR4 receptor. We will investigate the hypothesis that NE induces alphavbeta6 mediated TGFbeta activation via a TLR4 and RhoA mediated pathway, promoting collagen deposition in the lung. Specifically, we will determine the pathway through which NE induces alphavbeta6 integrin mediated TGFbeta activation in epithelial cells. Using models of injury in ne-/- and slpi-/- (SLPI is an inhibitor of NE) mice we will identify whether NE can signal to the alphavbeta6 integrin in the lung and whethe r this pathway is responsible for the protection from lung fibrosis observed in ne-/- mice. We will thus determine whether the fibrogenic effects of NE are mediated via the alphavbeta6 integrin, aiding the development of therapies that target active TGFbeta at sites of inflammation.
The mariner transposons are promising tools for the genetic manipulation of mammals. However, their precise mechanism remains the largest gap in our fundamental understanding of the DNA-based transposons. Progress on both fronts has been hindered by the unique properties of the different transposons. The most efficient system in vertebrates, has proven recalcitrant in vitro. Conversely, those elements active in vitro, perform poorly in mammalian cells. We propose to break this impasse using Hsmar1. Hsmar1 is highly amenable in vitro, and is presumably adapted to its mammalian host. The efficiency of mariner transposition appears to be limited by the stability and/or aggregation of the synaptic complex. We will investigate changes in the arrangement and stoichiometry of the subunits during assembly of the synaptic complex and intermediate stages of the reaction. This will address weather different subunits perform different functions, and whether this is dictated by their stru ctural placement within the complex. During this work we will generate mutations to improve solubility, transposon end binding and resistance to aggregation. Combined with improved physical methods for preparing the complex, this will facilitate structural studies. An atomic structure for the complex will permit direct engineering of the system for a number of practical applications.
Hadleigh Great War Centenary Project
Provide Walls of Honour for the fallen in the Town Memorial Park
Weekend D-Day celebration event 25 Jun 2004
The Gateshead branch of the Royal British Legion has been awarded a grant towards their weekend of celebrations in commemoration of the D-Day landings. This will involve a church service as well as entertainments and refreshments. The event is open to all residents in the Gateshead area.