The major research interests of the School lie within integrative cardiovascular and metabolic physiology and pharmacology, neuroscience, cell signalling, and biochemistry and cell biology.
The School has extensive interactions with colleagues throughout the world and across the University, particularly with the School of Pharmacy, the School of Graduate Entry Medicine & Health, and clinicians based in the Queen’s Medical Centre, Nottingham City Hospital, Derbyshire Royal Infirmary and Derby City General Hospital. This structure permits an interactive, multidisciplinary approach to research, combining molecular, biological and cellular investigations with integrated in vivo studies in both animals and man.
A key feature of our research environment is that it facilitates wide-ranging cross-fertilisation between areas of interest by the use of multiple experimental approaches. To this end, various specialist research facilities are established in the School, together with a spectrum of advanced equipment for biomedical analysis and data capture.
School members form part of the Centre for Integrated Systems Biology and Medicine within the Institute of Clinical Research. Their aim is to use integrated systems approaches to answer questions of clinical relevance relating to:
- Endothelium: mechanistic studies of endothelial function in health and disease; paracrine and autocrine regulatory roles of the endothelium, specifically the effects of vasoactive factors such as NO, EDHF, endothelins and VEGF, and their interactions with gap junctions.
- Placenta: placental function in normal and complicated pregnancies (IUGR, pre-eclampsia, diabetes) including quantitation of diffusive conductance, angiogenesis and trophoblast turnover using design-based stereology; ex vivo perfusion and molecular markers are used to define barrier and angiogenesis function.
- Neurohumoral Effectors: cardiovascular biology of angiotensins, vasopressin, novel peptides, purines, melatonin, and cannabinoids, in relation to vascular control, receptor mechanisms and post-receptor coupling.
- Endotoxaemia: quantitative assessment of vasodilator and vasoconstrictor mechanisms in endotoxemia, including cardiovascular/metabolic interactions.
- Energy Utilisation and Fatigue in Skeletal Muscle: the role of the pyruvate dehydrogenase complex (PDC), and of intramuscular carbohydrate, creatine, carnitine and lipid, on muscle function and fatigue development during contraction.
- Skeletal Muscle Atrophy and Growth: investigations of molecular events in skeletal muscle relating to atrophy, growth and contraction; skeletal muscle development.
- Human Energy and Macronutrient Metabolism: studies of carbohydrate utilisation at rest and during exercise; alterations in substrate use in obesity, diabetes and varied meal patterns in relation to insulin sensitivity and thermogenesis; factors regulating appetite and nutrient intake.
- Nutrient-Gene Interactions: the integrated effects of dietary fat and carbohydrate and dietary components, such as isothiocyanates, on the production, processing and actions of specific transcription factors that regulate gene expression.
School members form part of the Institute of Neuroscience. The Institute is able to facilitate high-quality, multidisciplinary, clinical and non-clinical neuroscience research. This group has access to a superb range of methodologies, ranging from molecular to whole animal and human studies to investigate:
- Animal Models of Mental Disease: early environmental influences on brain neurochemistry and function in relation to mental disorders including Alzheimer’s disease, ADHD, schizophrenia and depression, particularly the role of amine, amino acid and neuropeptide neurotransmission; neurogenesis during depression.
- Drugs of Abuse: mechanisms of reward and aversive behaviour, with particular reference to cannabinoids. Neurotoxicity and metabolites of ecstasy (MDMA).
- Pain Mechanisms: the roles of GABA, vanilloid and cannabinoid receptor systems in models of chronic pain.
- Neurodegeneration and Neurotoxicity: molecular mechanisms underlying chronic human neurodegenerative disorders, particularly the role of the ubiquitin/ proteasome pathway; mechanisms of reactive metabolite generation in drug toxicity and validation of alternative methods; neurovascular damage mechanisms; embryotoxicity.
- Hypothalamic Control of Puberty and Body Weight: the hypothalamic basis of energy metabolism; mechanisms involved in male reproductive maturation.
- Molecular action of neurotoxins: role of astrocytes in maintaining neuronal and vascular function and their involvement in the vulnerability and resistance to natural and chemically-mediated neurodegeneration; effects of hypoglycaemia on brain function.
School members form part of the Cell Signalling Group within the Institute of Pharmaceutical Sciences and Experimental Therapeutics. Their aim is to utilise the advances being made in molecular genetics and cell biology to study the regulation of cell signalling pathways in healthy and diseased human tissues. The major research themes within the group are
- Molecular Pharmacology and Cell Biology of Cell Surface Receptors: molecular pharmacology, regulation and signalling of G-protein-coupled receptors and tyrosine kinase-linked receptors.
- `Cross-Talk` Between Different Intracellular Pathways: synergistic interactions between G-protein-coupled receptors (GPCRs); interactions between GPCRs and tyrosine kinase receptors; cross-cascade signalling of proteins involved in gene transcription.
- Single molecule analysis of ligand-receptor interactions using fluorescence correlation spectroscopy: research on the development of fluorescent ligands for GPCRs.
- Use of bimolecular fluorescence complementation to investigate protein-protein interactions: investigation of receptor trafficking and receptor-effector interactions.
School members form part of the Centre for Biochemistry and Cell Biology (CBCB). Current research focuses on the molecular mechanisms of growth, development and adaptation in both health and disease. The techniques employed include molecular biology, cell culture, microinjection, proteomic analysis, microarray screening, advanced imaging techniques, molecular structure determination and modelling. Most of the research in the Centre is conducted in vitro or in tissue and organ culture. Increasingly, we expect to use computational analysis and simulation. One of the research groups in the Centre is especially dedicated to developing alternatives to animal experimentation. The Centre is heavily involved in the use and development of genomic, proteomic and imaging technologies in two of the technology clusters of the University (Post-genomic Technologies Cluster and Imaging Cluster). Also the Centre has strong links, through collaboration and shared technology, to the Institute of Genetics, the Institute of Neurosciences, the Centre for Integrated Biology and Medicine and the Institute of Experimental Therapeutics.
The Centre has particular strengths in the following areas:
- Signal transduction in proliferation and inflammation; intracellular trafficking
- Post-translational modification of transcription factors and chromatin remodelling
- Proteasome structure and function, neurodegeneration
- Ubiquitin, ubiquitin binding proteins, ubiquitin ligases and ubiquitin-like proteins
- Regulation of lipid metabolism
- Structure of membranes, membrane proteins and transport across membranes
- Cardiovascular development, cell adhesion and bacterial pathogens
- DNA recombination and repair
- Tumour suppression and protein trafficking
- Structure and function of STAT proteins.