Mission

The mission of the Functional Genomics Unit (FGU) is to use genomic information to determine mechanisms of disease in order to develop novel therapeutic approaches.  It is now well established that beneath the description of common neurological diseases as single clinical entities (e.g. motor neuron disease, Parkinson’s disease or Alzheimer’s disease) there are in fact a family of disorders each of which will be rarer in the population.  Developing treatments for such disorders will require an understanding of the common biochemical pathways which lead to malfunction and the development of a family of products for their treatment.  In the FGU we are combining the power of computational analyses and the latest experimental technologies in model organisms to reveal the roles of genes and genomes in health and disease.  The Unit is pursuing the translation of these discoveries into improved healthcare products and patient treatments via partnerships with clinicians as well as the Pharmaceutical and Biotechnology Industries.

Scientific Overview

• An improved understanding of genetic disease requires links to be forged between genotypes and patient phenotypes.  Professor Ponting's group’s research is leading to a better appreciation of genetic and genomic changes associated with obesity, Alzheimer’s disease, learning disabilities, and other neurological disorders.  The group also contributed substantially to international efforts that analysed the sequences of the human, mouse, rat, dog, marsupial, monotreme and chicken genomes. Further studies are focused on understanding the evolution and functions of non-coding RNAs, specifically those expressed in the brain.
• A number of diseases are known to be caused by aberrant RNA regulation but the molecular mechanism is still elusive.  Dr Liu’s group studies small RNA regulation in brain development and germ-cell development using the fruit fly Drosophila melanogaster as a model system. They are interested in how various small RNAs may be related and how the spatial dynamics of small RNAs influence gene expression in development and disease. Their studies provide an RNA angle to gain new insights into the cellular and molecular mechanisms for neurological and neurodegenerative diseases including spinal muscular atrophy and fragile X syndrome.
• The Sattelle lab uses the nematode C. elegans to model nervous system and neuromuscular degenerative disorders, with particular emphasis on amyloid related diseases, notably Alzheimer’s disease and inclusion body myositis.  The lab also studies nicotinic acetylcholine receptors, their roles in nervous system and neuromuscular disease and as targets for novel drug therapies.
• The Davies group is using animal models to study movement and behavioural disorders.  Research on Duchenne muscular dystrophy, the devastating muscle wasting disorder, is now at the translation stage; compounds that regulate the muscle protein utrophin have been developed for testing in clinical trials and we are developing novel vectors for exon skipping.  A second major programme studies mouse models of ataxia where defects in the development or function of the cerebellum occur. This is providing new insights into neurodegenerative pathways applicable to many neurological diseases. In addition, one ataxic mouse with a mutation in a synaptic protein is being investigated as a novel model of psychiatric disorders such as schizophrenia.
• Kevin Talbot's research group works on the molecular basis of motor neuron degeneration using cellular and mouse models. We are particularly interested in identifying why motor neurons are vulnerable to mutations in widely expressed genes, such as SOD1, TDP-43 and SMN, and in finding common links in the pathogenesis of disorders, like spinal muscular atrophy and amyotrophic lateral sclerosis. Our ultimate aim is to identify targets for the development of new drug treatments.

The FGU is embedded within the Department of Physiology Anatomy and Genetics and collaborates widely across the Medical Division of the University of Oxford. For example, Davies and Sattelle are active participants in the OXION ion channel initiative (click here for more information), headed by Professor Ashcroft. There are close links with computational modellers such as Professor Sansom in Biochemistry. Professor Ponting works closely with Drs Mott and Cookson in the Wellcome Trust Centre for Human Genetics. We collaborate with colleagues at the MRC Mammalian Genome Unit at Harwell on the use of mutagenesis programmes for the analysis of movement disorders. The FGU is a major contributor to the Oxford Parkinson’s Disease Centre (http://opdc.medsci.ox.ac.uk/) which was recently awarded £5m over 5 years by the Parkinson’s Disease Society to determine the earliest pathological pathways in Parkinson's disease.

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