Prof David Leach

Dean of Academic Excellence

Background

1980    D.Phil., Sussex University

1980 - 1982    SERC Postdoctoral Fellow, Department of Molecular Biology, University of Oregon

1982 - 1983    MRC Postdoctoral Fellow, Department of Molecular Biology, University of Edinburgh

1983 - 1998    Lecturer, Department of Molecular Biology, University of Edinburgh

1998 -2002    Reader, Institute of Cell and Molecular Biology, University Edinburgh

2002 - Present    Professor of Molecular Genetics, Institute of Cell and Molecular Biology, University of Edinburgh

2004 - 2008    Head of Institute, Institute of Cell Biology, University of Edinburgh

2008 - 2013 Head of School of Biological Sciences, University of Edinburgh

Undergraduate teaching

2nd year Genes and Gene Action

3rd year Molecular Genetics

4th year Biochemistry, Genetics and Molecular Biology

Research summary

http://leach.bio.ed.ac.uk/

Maintaining Genome Stability:

Applications and Implications of DNA Misfolding to Genetic Recombination, DNA Repair and Chromosome Segregation

The maintenance of genome stability relies on the interaction of DNA replication, repair and recombination, and it is becoming increasingly apparent that these are interconnected processes. Understanding of these processes promises to underpin our ability to respond appropriately to problems of wide importance such as genetic disease, cancer and ageing. Our interest in this field has led us to concentrate on a form of endogenous DNA damage - mis-folded DNA. DNA with internal symmetry (e.g. inverted repeats and simple sequence direct repeats) can mis-fold and cause genetic instability. This is a serious problem since DNA sequences with internal symmetry (e.g. tRNA sequences) are essential for life and simple repetitive sequences are common, can cause genetic diseases (e.g. Huntington's disease, myotonic dystrophy and fragile-X syndrome) and are rearranged in many cancers. We have developed assays for DNA mis-folding in living cells; initiated the study of the genetics and biochemistry of the E. coli SbcCD nuclease (Rad50/Mre11 in eukaryotes) which attacks mis-folded DNA; studied the pathway and consequences of double-strand break repair initiated by SbcCD-mediated cleavage; and are beginning to unravel the complex processing of trinucleotide repeats using E. coli model systems. Our aim is to generate an integrated understanding of replication, repair and recombination that goes beyond their initial discoveries as independent "pathways" and contributes to our understanding of how genome stability is maintained.

We are currently in the exciting position of using DNA misfolding as a tool to investigate the mechanisms of genetic recombination, DNA repair and chromosome segregation at defined chromosomal sites and welcome approaches from students interested in pursuing PhD studies and from postdoctoral scientists interested in contributing to this work.

View all 34 publications on Research Explorer