1977 - Present University of Edinburgh
1974 - 1977 Postdoctoral Fellow, Department of Biochemistry, Stanford University
1972 -1973 Postdoctoral Fellow, Genetics Laboratory, University of Oxford
1972 PhD, Department of Molecular Biology, University of Edinburgh
Transposable elements are DNA sequences that move from one place to another within a genome. The availability of complete genome sequences has revealed the significant role that these elements play in genome evolution, organization and stability. They make up a substantial proportion of most genomes, over 40% in the case of the human genome. We have studied several aspects of the molecular biology of transposable elements and are particularly interested in how they transpose and how transposition is regulated. To this end we are using two transposable elements from Drosophila, the I factor, an element related to the LINE 1 elements that make up nearly 20% of the human genome, and mariner, an element related to those being developed as vectors for transgenesis and gene therapy.
The I factor is a non-LTR retrotransposon that transposes in the female germ-line where its RNA transposition intermediate is transported along microtubules to the oocyte nucleus. Our current research, done in collaboration with Prof Ilan Davis in the University of Oxford, is directed towards understanding the cellular processes required for this transport, how transport of I factor RNA is related to transport of other RNAs within the cell, the steps in transposition that occur once this RNA has reached the nucleus, and the role that I factor encoded proteins play in transposition.
The mariner transposon moves by a cut and paste mechanism during which a mariner encoded protein, transposase, excises it from one position in the genome and inserts it at another. Mariner transposase is a member of a family of enzymes that includes transposases of transposons found in bacteria, plants and fungi, retroviral integrases and the RAG recombinase that mediates immunoglobulin gene rearrangement. We are studying the steps, in transposase action biochemically, and in conjunction with Dr Julia Richardson and Prof Malcolm Walkinshaw in Edinburgh we are investigating this mechanism at the structural level.