Associate Professor in Mitochondrial Biology, Faculty of Medicine & Health Sciences
I received a BSc (Hons) in Zoology from the University of Leeds and went on to work with Kay Davies at the now David Weatherall Institute (IMM) to help decipher the molecular basis of X linked mental retardation. My research in this area led to a D.Phil in Biochemistry from the University of Oxford. Postdoctoral work took me to the USA to work with Leroy Hood in the Department of Biotechnology at the University of Washington in Seattle. A subsequent postdoctoral appointment was spent at the MRC Prion Unit at the University of London. In 2007 I was promoted to Research Assistant Professor in the Department of Laboratory Medicine at the University of Washington, Seattle where I established my current research interest in the molecular basis of neurodegeneration. In 2010 I was appointed Lecturer in Protein Biochemistry at the School of Veterinary Medicine and Science at the University of Nottingham.
My practical expertise includes mitochondrial complex assays, carboxypeptidase assays, recombinant protein production, 2D gel electrophoresis, Western blotting, immunostaining, live cell imaging, RFLP analysis, primary neuron culture, retinal histology, comparative biology genes and proteins.
I also have academic experience in
Genetics, gene identification and expression analyses in mental retardation and also FTD3 dementia. Microarray analysis using gene ontology groups in dementia and ataxia. Mutation detection and characterisation of animal models of neurodegenerative disease. Genomics and genome-wide association studies in complex disease - Rheumatoid Arthritis and Prostate Cancer. Linkage analysis software development. Proteomics of complex mixtures by unlabelled mass spec approaches and 2D gel electrophoresis. Lipidomics data analysis. Molecular pathway determination. Electron microscopy of neural tissues undergoing autophagy and mitophagy.
At undergraduate level I teach mostly within the neuroscience module. Other teaching includes biochemistry of proteins, cell biology, cell death, liver function and enzyme kinetics. I also supervise… read more
My current research interests focus upon understanding the molecular basis of neurodegeneration. The cost of managing neurodegenerative disease is currently calculated at EUR 72 billion annually.… read more
At undergraduate level I teach mostly within the neuroscience module. Other teaching includes biochemistry of proteins, cell biology, cell death, liver function and enzyme kinetics. I also supervise a number of undergraduate research projects - mostly in the areas of mitochondrial biology of ageing and degeneration. Working in the Vet school I have access to materials that allow comparisons between many different species at the protein and biochemical level.
My current research interests focus upon understanding the molecular basis of neurodegeneration. The cost of managing neurodegenerative disease is currently calculated at EUR 72 billion annually. However, treatment for these disorders is limited, mostly consisting of perfunctory symptom control - often with undesirable side effects in both the short and long term. Risk of neurodegeneration for an individual increases with age, and the proportion of the European population aged over 65 is likely to rise to 25% by 2030 (from 16% today). Therefore, the incidence of these conditions, as well as the social and financial costs of treating them, is set to rise steeply in the coming years. Better strategies for prevention and treatment must be sought as a matter of urgency. Neurodegenerative diseases typically have a slow insidious onset and the course of disease is often lengthy.
We are using 'omics' technologies, together with imaging techniques to analyse the changes that occur in neurons which eventually lead to their demise. We have identified the importance of the protein NNA1/ CCP1 for cerebellar health and how genetic changes can alter the expression or stability of the protein. We have also looked using ultrastructural methods and found that a process known as autophagy is occurring in a dramatically different way in affected neurons when compared with normal brain. Much of what we have found appears to also apply to the degenerating retina such as is found in the human disease Retinitis Pigmentosa. Our findings using a model of neurodegenerative disease have provided detail in areas such as the involvement of mitochondria in these disorders. In the case of neurodegeneration it is difficult to gain a clear insight into presymptomatic disease and early events. Post mortem brain and retina provide only a snapshot of a ravaged tissue with elevated markers of cell death and inflammation. I am interested in studying the cusp of development to maturity gained in the neuron, revealing the cause of the disease process rather than the result. The retina degenerates more slowly in the majority of retinal disease processes in humans. By gathering data at a pre/early symptomatic stage we gain advantage over a tissue already depleted of affected neurons. Our studies allow the possibility of moving towards therapies that can be applied before neuronal loss leads to symptomatic disease, a far preferable approach than to try and repair the damage once disease has run its course.
Previously I have been interested in finding and characterising genes responsible for mental retardation, developmental delay and dementia. I have also used methods of genetic linkage analysis to locate susceptibility loci for complex diseases such as prostate cancer, rhuematoid arthritis and diabetes. Characterisation of a classic, spontaneous model of neurodegeneration (Purkinje Cell Degeneration) has lead to an interest in the mitochondrial basis of disease and an analysis of the interplay between age and degenerative processes.
My interest is heading towards a more complete understanding of the cellular organelle that is central to biological energy - the mitochondrion. We will be looking at normal mitochondrial biology, throughout the lifespan, in different species. We contrast what we see 'normally' with the situation in disease to understand the possibilities, flexibility and compensatory mechanisms in biological systems.
Defining the parameters within which an organism works best will allow us to achieve therapy and cure.