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- Professor of Molecular Cell Biology
- ICH Genetics & Genomic Medicine Prog
- UCL GOS Institute of Child Health
- Faculty of Pop Health Sciences
I am interested in disease caused by genetic changes and how study of these mutations and their effects can reveal important and complex aspects of cell biology that may otherwise be beyond current appreciation. I make use of model systems.
My main research interest is the neuronal ceroid lipofuscinoses (NCL) or Batten disease, a group of inherited neurodegenerative diseases that affect lysosome homeostasis. This group of diseases are rare but understanding their biology may open new avenues for understanding more common neurodegenerative conditions as well as the basic biology of cells. When I began this work none of the genes had been identified so this was my initial focus. Fourteen genes have now been identified. I continue to work closely with others whose aim is to identify the remaining NCL disease genes by pooling resources and expertise. I curate the NCL Resource web site, which acts as a gateway for Batten disease and includes the Mutation Database which I maintain on behalf of the international NCL community (http://www.ucl.ac.uk/ncl).
Within my own laboratory I have a particular interest in the biology of CLN3, a highly conserved gene, and of CLN6 and CLN8, vertebrate genes, whose functions remain elusive. There is no current therapy for disease caused by variation in these genes. We currently use mammalian systems and the model organism Schizosaccharomyces pombe and have studied their location, topology, trafficking signals, interacting partners and effect on cells of complete loss of function. The function of CLN3 is complex and more important than was expected, and the fission yeast model system has revealed novel aspects of its function including a role upstream of the lysosome. We discovered that an intragenic deletion of CLN3 shared by most patients with juvenile NCL does not completely abolish CLN3 function, which has important implications for future therapy development. We use various screening strategies to identify genes and small molecules that restore defects associated with aberrant or loss of NCL gene function. We are developing a therapy that targets the visual loss in NCL since this would significantly improve the quality of life of affected children, with the ultimate target being the brain.
Keywords: Brain, Dementia, Epilepsy, Genetics, Macula, Modelling, Neurodegeneration, Neuron, Neuroscience, Vision
Conditions: Batten disease, Batten's disease, Neurodegenerative diseases
Methods: Bioinformatic analysis, Cell culture, Confocal microscopy, Electron Microscopy, Enzyme assays, Genetic manipulation (including knockout/knockin) , Genetic screens, Genomic analyses, Light microscopic techniques, Linkage, Mapping and positional cloning, Protein transport/localisation, Recombinant protein expression, Time-lapse imaging, Other
|01-APR-2017 – 31-MAR-2020||Great Ormond Street Hospital Children’s Charity Professor||UCL Great Ormond Street Institute of Child Health||University College London, United Kingdom|
|01-OCT-2004 – 30-SEP-2016||Reader in Molecular Cell Biology||MRC Laboratory for Molecular Cell Biology||University College London, United Kingdom|
|01-OCT-1997 – 30-SEP-2004||Senior Lecturer in Molecular Genetics||Paediatrics and Child Health||UCL, United Kingdom|
|01-OCT-1992 – 30-SEP-1997||Lecturer in Molecular Genetics||Paediatrics||UCL, United Kingdom|
|1987||MA||Master of Arts – Natural Sciences||University of Cambridge|
|1986||PhD||Doctor of Philosophy – Biochemistry||Imperial College of Science, Technology and Medicine|
|1983||BA Hons||Bachelor of Arts (Honours) – Natural Sciences||University of Cambridge|