- 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
We have established that bacterial cells require cellular homeostasis for growth and survival in diverse niches. Ion channels play major roles in cellular homeostasis, as exemplified by our previous work on mechanogated (MscS & MscK) and electrophile activated (KefC) channels. We have made considerable progress in understanding the gating of these two channel types and the future programme will concentrate specifically on the gating transitions in the channels. Additionally, we will pursue high resolution structures for the closed state of both MscS and MscK and assess important regions of the KefC structure in order to link them to function. The team members have become expert in electrophysiology, molecular genetics and protein biochemistry and they have made significant contributions to understanding the mechanisms and physiological roles of bacterial ion channels. The programme builds on these core skills, which will be augmented by strategic structural and biophysical collaborations (Naismith & Perozo). The key objectives will be:(a) Detailed understanding of the gating transitionof the MscS and MscK channels.(b) Closed structures for MscS and MscK.(c) Structural analysis of KefC - definition of the ion translocation pathway and the gating transition.
Effects of in-utero exposure to environmental chemicals via maternal pasture ingestion on fetal development. 11 Jul 2006
Current understanding of possible detrimental effects of exposure to environmental chemicals (ECs) on fetal reproductive development relies on toxicological studies of short-lived rodents exposed to high doses of single/small numbers of compounds. We will employ a long-lived species, the sheep, to investigate effects on fetal development of a real-life , chronic, low-level exposure of ewes to a relevant cocktail of ECs, including endocrine disrupting compounds (EDCs and heavy metals. Ewes will be maintained on pastures fertilised with either inorganic fertiliser (Control) or sewage sludge (EC cocktail). Maternal and fetal EC levels will be measured and related to endocrine systems and hypothalamo-pituitary and gonadal development and function at 55 & 110 days of gestation, and in adult offspring. Specific effects of fetal exposure via continuing maternal intake of ECs will be distinguished from those solely due to mobilisation of maternal EC loads. This will be done by switching Contr ol ewes to sewage sludge-fertilised pastures, and vice versa, immediately prior to mating, with slaughter at 110 days of gestation and measurements as above. Our key goals are to determine the extent to which EC exposure (1) disrupts fetal development, (2) compromises adult reproductive function and (3) relies on mobilization of maternal EC loads.
Student electives for Justine Downing, Jennifer Muir, Michelle Perera and Wendy Thomson. 19 Jul 2006
Architecture of the genome: a genetic investigation of chromosome-positioning mechanisms. 16 May 2007
The intranuclear organization of chromosomes is critical for many aspects of genome function, affecting gene expression, DNA repair, and the organization of DNA replication. It is therefore imperative that we understand the mechanisms and cellular components that control chromosome architecture. We have pioneered a screening method that combines advanced imaging with yeast genetics to identify cellular components important for chromosome positioning, using a microscope system funded by a recent Wellcome Trust Equipment grant. Our pilot analysis has identified the chromatin assembly factor Asf1 and the Ctf18 ring-loading complex as crucial for correct positioning of the chromosome ends or telomeres. The first objective of this research programme is to use genetic, genomic, and proteomic approaches to understand the mechanisms by which Asf1 and Ctf18 affect telomere positioning. Second, we will undertake a genome-scale survey of the cellular components responsible for positioning and organizing telomeres. The information gained will contribute to the third part of the programme, in which we will analyse the localisation of non-telomeric chromosome domains, and identify the molecular components involved in global chromosome positioning. Overall, this research programme forms a cutting-edge investigation of the mechanisms controlling eukaryotic chromosome architecture.
Regulation of vascular smooth muscle cell phenotype by changes in phospholipase C gamma expression: relationship to the pathogenesis of vascular disease. . 22 Feb 2007
The molecular mechanisms regulating vascular smooth muscle (VSM) cell proliferation during vascular disease are not well understood. These mechanisms regulate selective gene expression leading to changes in protein expression necessary for proliferation. A previous study, and further preliminary evidence, has indicated that phospholipase C gamma (PLCg) expression is regulated dependent upon VSM phenotype both in vitro and in vivo. This study will examine the hypothesis that these changes in PL Cg expression can act as a molecular switch and regulate VSM phenotype towards either proliferation or differentiation. It is proposed that this mechanism occurs via the selective activation of the Ca2+-dependent phosphatase, calcineurin and subsequent regulation of key transcription factors. Experiments will use overexpression/knockdown of PLCg in cultured VSM cells to determine how changes in growth factor-stimulated pathways correlate with altered PLCg expression. These pathways will inc lude Ca2+ signalling, transcription factor activation/interaction and ultimately regulation of gene expression and growth. Further experiments will test the validity of this hypothesis using an in vivo vascular injury model. This study will uncover an important mechanism in regulating VSM phenotype and will further demonstrate that this may be involved in the development of vascular disease.
Neurodegenerative diseases pose one of the largest challenges in both the clinical and the research setting. My group has investigated the fundamental mechanisms underpinning cell death in Parkinson's disease (PD), which originates from the loss of dopaminergic neurons. We have demonstrated that cyclooxygenase (COX)-2 expression is increased in dopaminergic neurons in the substantia nigra pars compacta of PD patients (Teismann et al., PNAS 2003). In our Parkinson's disease model, mice treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), equivalent observations were made. COX-2 is instrumental in MPTP-induced neurotoxicity but our data suggest that the mechanism is not mediated by inflammatory cells (microglia/astrocytes). Our data are consistent with a major role for prostaglandin (PG) E2. Thus, COX-2 activity is paralleled by an increased expression of PGE2 in dopaminergic neurones. PGE2 can induce cytokine release and deprive the cell of oxygen, thus leading to cell death. In the proposed project we will investigate the function and mechanisms of PGE2 in the
Chitin is an essential molecule in the cell walls of all fungi and invertebrates that challenge human health. In fungi, chitin and a second polysaccharide, beta(1,3)-glucan, form the core of the wall skeleton, and since neither molecule is found in humans they represent specific targets for chemotherapy. However cell wall synthesis is carefully regulated by fungi and they have elaborate salvage mechanisms to protect the integrity of their cell walls. This project investigates the regulation of c hitin synthesis in the fungal pathogen Candida albicans in terms of newly identified mechanisms that (a) regulate the normal localisation of chitin synthase enzymes and (b) modify wall synthesis to rescue the cell under conditions of stress. The specific goals are therefore: (i) to exploit and test the hypothesis stemming from our observation that spatial control of chitin synthesis is regulated by phosphorylation of chitin synthases; (ii) to investigate the spatial regulation of chitin synthesi s and septum formation under conditions that rescue cells from cell wall damaging agents; (iii) to test whether combinations of chitin synthase and cell wall beta(1,3)-glucan synthase inhibitors can overcome the rescue mechanisms in vivo leading to antifungal chemotherapies of enhanced efficacy.
'Varieties of Cultural History: Theory and Practice in the Cultural Histories of Medicine, Science and Literature and the Arts' conference to be held at the University of Aberdeen from 5 - 8 July 2007. 23 Mar 2007
Varieties of Cultural History: Theory and Practice in the Cultural Histories of Medicine, Science, Literature and the Arts Cultural History is a diverse field, drawing inspiration from many disciplines beyond conventional history: thus, the question 'What is Cultural History?' is one that cultural historians regularly encounter both at research and teaching levels. By providing a forum for creative interchange among practitioners of cultural history, in and beyond the spheres of medicine and health, this conference provides an opportunity to reflect upon and identify characteristics, approaches, methods and ambitions. Cultural historians of medicine and health have consistently played major roles in debates over such questions, their work repeatedly providing some of the most provocative, innovative, or otherwise effective examples of what the approaches, methods and ambitions of cultural history may achieve. In light of this, the organisers have foregrounded 'medicine' in the list of 'varieties of cultural history' that the conference will explore. Our wish is that at this conference, cultural historians of medicine will disseminate their own research to a more extended community of scholars; and, reciprocally, that scholars beyond the conventional limits of cultural history of medicine (in science, literature and the arts) will highlight the resonances between medicine, health and wider culture. The first two full days of the conference will consist of parallel sessions and keynote papers; the morning of the third day will consist of the discussion of varieties of cultural history teaching, in the research contexts of different institutions. During the afternoons of 6 and 7 July there will be four commissioned sessions of three papers, two of which will cover the cultural history of medicine, and six keynote papers, one of which will be by a cultural historian of medicine. The other commissioned sessions will cover 'Science and Literature' and 'Methodological Problems in the Cultural History of Science'.
High pressure freezer. 01 Jul 2008
High pressure freezing (HPF) is the gold standard method for high fidelity fixation of biological material for electron microscopy. We have already acquired more than half of the funds required for this equipment and we request the residual support required this application. HPF an extremely rapid, method for the immobilization and fixation cells and tissues and is particularly well suited for ultrastructural examination of microbial cells and human tissues that are difficult to fix by conventi onal non-cryo-methods. Samples thus prepared are also ideal for ultrastructural studies of tissue composition by immunolocalisation. Recently launched HPF equipment achieves a much larger depth of freezing and offers attachments that allow correlative microscopy, whereby structures identified by fluorescence labelling are subsequently examined (after HPF) in the electron microscope. It is well known that fungal cells and human skeletal tissues that we work with are notoriously difficult to pr epare for ultrastructural analysis. They are poorly preserved by conventional fixation protocols and specimens are prone to shrinkage, and the loss and rearrangement of labile components. The two major research programmes leading this application have extensive requirements for high quality imaging. The equipment would also be used by an extended group of Wellcome funded staff at Aberdeen.
Hadleigh Great War Centenary Project
Provide Walls of Honour for the fallen in the Town Memorial Park