Professor Peter McGlynn

Anniversary Chair

Overview

All organisms must make accurate copies of their genetic material, DNA, every time one of their cells divide and this requirement has driven the evolution of very complex multi-subunit enzyme machines to replicate DNA. However, these machines are not perfect and break down frequently, requiring some form of repair to allow accurate completion of DNA copying. Failures in these processes cause DNA mutations that can have catastrophic consequences for survival which, in organisms such as ourselves, include the development of genetic disease and cancer. Conversely, inhibiting DNA copying in bacteria using antibiotics is an important tool in our fight against infection. Our long-term aims are to understand why these copying machines break down, how they are repaired and the reasons why this repair sometimes goes wrong and causes mutations.

We harness the very powerful biochemical and genetic tools available in the bacterium Escherichia coli to dissect DNA copying mechanisms. We are also studying individual DNA copying machines using cutting-edge imaging techniques in collaboration with Prof. Mark Leake here in York to visualise how single protein molecules function inside cells. One aspect of our work is to characterise the relative importance of different barriers to DNA copying machines inside cells. We also seek to understand how motor enzymes called helicases can help propel the replication machinery along the DNA. We have identified such a motor enzyme in E. coli and have demonstrated that this accessory motor helps to sweep potential barriers out of the path of the advancing DNA copying machinery, analogous to a snow plough moving along a road. Currently we are attempting to understand how this type of nanomotor can push potential barriers off the DNA. A third aspect of our work seeks to understand how a different class of accessory factor, recombination proteins, can help to repair the copying process when it fails and what happens when this type of repair goes awry. Finally, in collaboration with Prof. Rod Hubbard in York, we are developing new approaches to inhibit DNA copying in bacteria by identifying "weak spots" within the bacterial copying machinery that might lead to the development of novel antibiotics.


A molecular model of DNA at the point of replication, derived from single molecule fluorescence analyses in collaboration with Steven Magennis, University of Manchester.

DNA Model

Structure of the E. coli motor (Rep) bound to DNA (PDB 1UAA). This enzyme displaces blocks from the DNA ahead of the advancing replication machinery by tracking along a single DNA strand, depicted here in red.

 E.coli Motor Structure

Profile

YearPositionLocation
2012- Anniversary Chair in Biology

Department of Biology, University of York

2003-2012 

Reader and Lister Institute-Jenner
Research Fellow/Personal Chair
School of Medical Sciences,
University of Aberdeen

2000-2003

Lecturer and Lister Institute-Jenner
Research Fellow
Institute of Genetics,
University of Nottingham

1996-2000

Postdoctoral Research Associate Institute of Genetics,
University of Nottingham

1993-1996

Postdoctoral Research Assistant Department of Molecular
Biology and Biotechnology,
University of Sheffield

1992-1993

Postdoctoral Research Assistant AgBiotech Center, Rutgers
University

1989-1992

PhD University of Sheffield

1986-1989

BSc University of Sheffield

Publications


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McGlynn Peter

Contact details

Prof. Peter McGlynn
Department of Biology
University of York

Tel: +44 (0)1904 328688
Fax: +44 (0)1904 328505