Oxford University Department of Biochemistry
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Andreas Russ
Genetic modelling of human disease and drug action

Co-workers: Tobias Langenhan, Lamia Mestek, Simone Proemel, Helen Waller

Genome sequencing has identified many novel candidate drug targets and potential disease genes. Genetic analysis in model organisms is essential to investigate these genes in their physiological context, thus providing a crucial link from bioinformatics, biochemistry and cell biology to function in the whole organism. My group is using complementary mutagenesis strategies in model organisms to establish predictive models of human disease and to identify new targets for therapeutic intervention.
We have recently established subtle mutations in cytoplasmic dynein as new models for motor neuron disease, implicating this large molecular motor complex in the pathogenesis of neurodegeneration. We are studying the function of dynein by mutagenesis and imaging of dynein-based transport in living neurons, with the aim of modeling the functional changes in neurodegeneration.

In search of new drug targets we are working on a systematic analysis of “druggable gene families” in the human genome and the genomes of model organisms. These genes encode proteins that are amenable to therapeutic intervention by pharmaceutical compounds. Genome sequencing has uncovered a significant number of new members of these gene families, designated “orphans” because they have not been linked yet to specific biological functions. We perform systematic mutational analysis of these orphan genes to identify the most promising targets for novel drugs, currently focusing on an unusual subfamily of G-protein coupled receptors that is highly conserved in evolution.


Research Images

Expression of DYRB1::GFP in the ventral nerve cord of the nematode C.elegans. A transgene encoding a protein fusion between a dynein light chain and green fluorescent protein shows a clustered distribution and induces local swelling of neuronal processes

Expression pattern of a related receptor in neurons at a later stage of nematode development. The top panel shows standard light microscopy, the bottom panel shows the fluorescence of the transgenic reporter gene, and the middle panel the overlay of the two pictures

Expression of a putative G-protein coupled receptor during embryonic development of the mouse. Expression of the transgene labels a subset of cells in the somites, segmental structures of the embryo giving rise to muscle, bone, and skin



Expression pattern of a putative G-protein coupled receptor during early embryonic development of C.elegans. The promoter region of the gene under investigation was used to express green fluorescent protein in a transgenic construct. Numbers indicate developmental stage (minutes after fertilization)

Contact: andreas.russ@bioch.ox.ac.uk

Graduate Student and Postdoctoral Positions: No positions currently available

Website: http://users.ox.ac.uk/~magd1983

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