Professor Jon R Sayers, FSB

Professor of Functional Genomics

Professor JR Sayers

Department of Infection and Immunity
Henry Wellcome Laboratories for Medical Research
L Floor
The University of Sheffield Medical School
Beech Hill Rd
Sheffield S10 2RX

Tel: +44 (0)114 271 3027
Fax: +44 (0)114 226 8898
Email: j.r.sayers@sheffield.ac.uk
Secretary - Jean Lazenby
Tel: +44 (0)114 271 2237
Email: j.lazenby@sheffield.ac.uk

Biography

I teach graduate classes in biochemistry, protein/DNA sequence analysis, protein engineering of novel therapeutics and biotechnology. I studied Chemistry at the University of Birmingham, obtaining my B.Sc. in 1983 where I went on to gain a Ph.D. (1986) in the Nucleic Acids Groups directed by Prof. Stan Jones and Prof. Dick Walker. Thesis title; Synthesis of Nucleoside Analogues. In 1986 I joined the Max-Planck-Institut for Experimental Medicine, Gottingen, Germany under Prof. Fritz Eckstein as a postdoctoral researcher where I studied restriction endonuclease-DNA interactions and helped develop a widely used system for site-directed mutagenesis (the 'phosphorothioate approach'). I also became interested in flap endonucleases, or 5'-3' exonucleases. In 1991 I moved to a Lectureship in the Biochemistry Department at the University of Wales, Bangor, UK, where I established a research group working on various aspects of molecular recognition. Projects included work on novel phage T5 proteins, a schistosomal protease (in collaboration with Dr. Mike Doenhoff), genetic variability of Haemophilus influenzae (in collaboration with Dr. Tony Howard, PHLS Cardiff), generation of new binding proteins and flap endonucleases. I moved to Sheffield in 1995, was promoted to Senior Lecturer in 1997, to a Readership in 1999 and a personal chair in 2006. I have developed an interest in proteins secreted by Gram negative bacterial pathogens and how they interact with the host. We use a wide range of molecular and cell biological and biophysical techniques to unravel the detail of such interactions aided by close collaboration with structural biologists in Sheffield and the United States.  I was elected as a Fellow of the Society of Biology in 2013.

In 2001 I become a director and co-founder of Asterion Ltd., a biotech spin-off company (see Asterion Ltd.)

I have written an article for "The Biochemist" describing the trials and tribulations of an academic involved in the setting up of a spin-out company. It can be found under 'downloads'.

Research Interests

The group is involved in four main areas:

  • Molecular mechanisms involved in protein:DNA interactions.
  • Microbial proteases, pathogenesis and the host response.
  • Novel applications of biotechnology to biomedical research and drug development.
  • Structure-based drug design.

Ongoing topics include the following:

Mechanistic Studies on 5'-3' Exonucleases

A novel helical arch discovered in a 5'-3' exonuclease could explain how this class of essential replicative enzymes digest their nucleic acids substrates. See Ceska, Sayers, Stier & Suck (1996) Nature, 382, 90-93.

These enzymes are involved in replication of the lagging strand during DNA synthesis and in repair of DNA damage. Some members possess structure-specific endonuclease activity as well as exonuclease and RNase H activities. We have shown that a member of this important class of enzymes contains a novel DNA-binding motif, the helical arch (see above picture of the T5 exonuclease). We are using site-directed mutagenesis, crystallography and kinetic studies to determine how these complicated enzymes function. We have cloned and expressed a number of exonucleases from bacteria including the human pathogen Haemophilus influenzae. In collaboration with Dr. Dietrich Suck and Dr. Tom Ceska at the EMBL (Heidelberg) a structural model is emerging for this interesting group of enzymes. This work is funded by the BBSRC, The Wellcome Trust and the White Roses Consortium.

Protein-DNA Recognition

Many important biological processes such as gene expression are regulated by proteins binding to specific DNA sequences. We are studying novel DNA-binding proteins from viruses and pathogenic bacteria. We have chosen proteins with no sequence homologues in the databases. Such proteins are thus unique and studying how they recognize their target sequences should provide new insights into molecular recognition processes. This work is funded by the Bardhan Trust for Educational Research.

Significance of IgA1 Proteases in Pathogenic Neisseria meningitidis and Haemophilus influenzae

We have discovered a strong link between carriage of gene containing a highly variable domain and pathogenesis in these two meningitis-causing organisms. Collaborative work is underway with Dr. Tony Howard (PHLS, Bangor) and Professor Robert Read (Infection & Immunity, Sheffield). We have recently reported data demonstrating that pathogenic strains of Neisseria meningitidis produce higher levels of an enzyme capable of destroying human antibodies. The protease attacks IgA1, a major component of the mucosal immune system. This work has been funded by The Meningitis Research Foundation and the Colin Beattie Memorial Fund and is currently supported by the Medical Research Council.

Immunogenicity of a Schistosomal Protease.

Around 200,000 people die each year as a result of infection with S. mansoni. In a collaboration with Dr. Mike Doenhoff, University of Wales, we have expressed a recombinant protease from S. mansoni and are studying its antigenicity.

Teaching Interests

I teach graduate-level biochemistry, molecular & structural biology, bioinformatics and biotechnology in relation to biomedical research and drug discovery.

Professional Activities

Patents

  • Ross R, Artymiuk P, Sayers J.  Growth hormone fusion proteins. 2012, Granted US Patent No. 8,293,709.
  • Ross R, Sayers J, Artymiuk P.  Cytokine polypeptides and antibodies containing a signal sequence for the attachment of glycosylphosphatidylinositol, 2009, Granted US Patent No. 7625998.
  • Ross R, Sayers J, Artymiuk P.  Modified growth hormone fusion polypeptides, 2009, Granted US Patent No. 7524649.

Publications

For Key Publications see below. For a full list of publications click here

Journal articles