Professor Jon R Sayers

FRSB

Department of Infection, Immunity and Cardiovascular Disease

Professor of Functional Genomics

Professor Jon Sayers
j.r.sayers@sheffield.ac.uk
+44 114 215 9552

Full contact details

Professor Jon R Sayers
Department of Infection, Immunity and Cardiovascular Disease
L Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX
Profile

For enquiries, please contact – iicd-operational@sheffield.ac.uk

I teach graduate classes in biochemistry, protein/DNA sequence analysis, protein engineering of novel therapeutics and structure-based drug discovery.

I studied Chemistry (University of Birmingham, B.Sc. 1983) where I went on to gain a Ph.D. (1986) in the Nucleic Acids Group. Thesis title; Synthesis of Nucleoside Analogues. In 1986 I joined Fritz Eckstein’s group (Max-Planck-Institute for Experimental Medicine, Goettingen, to study restriction endonuclease-DNA interactions and helped develop a commercial 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. 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 Royal 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.) and founded DeFENition Ltd in 2016 to develop inhibitors of essential bacterial enzymes as candidate antimicrobial agents. The latter builds on over thirty years of experience in mechanistic enzymology of flap endonucleases.

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 the Publications, All publications tab below.


COVID-19

My laboratory responded to the Covid-19 pandemic by manufacturing large quantities of SARS-CoV-2 Nucleocapsid protein (both native and His-tagged) for use in diagnostics. We have made these proteins cheaply available via the University's website. 

Research interests

The group is involved in four main areas:

  • Structure-based drug design to generate new antimicrobial agents
  • Molecular mechanisms involved in protein:DNA interactions
  • Microbial proteases, pathogenesis and the host response
  • Biotechnology for biomedical research and drug development

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 by a DNA threading mechanism. 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. Early mechanistic work has been funded by the BBSRC, The Wellcome Trust. Translational research in this area has been funded by Innovate UK, The Department of Health and Social Welfare and DeFENition Ltd.

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.

Significance of IgA1 Proteases in Pathogenic Neisseria meningitidis and Haemophilus influenzae

We discovered a strong link between high levels of IgA1 protease production and pathogenesis in Neisseria and Haemophilus two meningitis-causing organisms. The protease attacks IgA1, a major component of the mucosal immune system. This work has been funded by The Meningitis Research Foundation, Colin Beattie Memorial Fund and the Medical Research Council.

Publications

Show: Featured publications All publications

Journal articles

All publications

Journal articles

Chapters

  • Sayers JR (2006) Bacteriophage T5 In Calendar R (Ed.), The Bacteriophages (pp. 268-276). Oxford University Press RIS download Bibtex download
  • Sayers JR & Eckstein F (1997) Phosphorothioate-based site-directed mutageneis In Creighton TE (Ed.), Protein function (pp. 279-295). Oxford University Press, USA RIS download Bibtex download
  • Sayers JR & Eckstein F (1991) Phosphorothioate-based site directed mutagenesis In McPherson MJ (Ed.), Directed mutagenesis (pp. 49-59). Oxford University Press, USA RIS download Bibtex download
  • Sayers JR & Eckstein F (1988) Phosphorothioate-based oligonucleotide-directed mutagenesis In Setlow JK (Ed.), Genetic Engineering (pp. 109-122). Plenum Pub Corp RIS download Bibtex download

Conference proceedings papers

  • Ferrandis E, Pradhananga SL, Touvay C, Kinoshita C, Wilkinson IR, Stafford K, Wu Z, Strasburger CJ, Sayers JR, Artymiuk PJ & Ross RJ (2010) Immunogenicity, Toxicology, Pharmacokinetics and Pharmacodynamics of Growth Hormone Ligand-Receptor Fusions.. ENDOCRINE REVIEWS, Vol. 31(3) RIS download Bibtex download
  • Kostidis K, Bardhan KD, Potter CW & Sayers JR (2007) Comh: Isolation, purification and characterisation of a unique H-pylori protein. GASTROENTEROLOGY, Vol. 132(4) (pp A212-A213) RIS download Bibtex download
  • Kostidis K, Thackray P, Bardhan KD, Potter CW & Sayers JR (2007) ComH: Isolation, purification and characterisation of a unique H pylori protein. GUT, Vol. 56 (pp A55-A55) RIS download Bibtex download
  • Kostidis K, Thackray P, Bardhan KD, Potter CW & Sayers JR (2005) ComH: Purification of a unique H pylori protein. GUT, Vol. 54 (pp A86-A86) RIS download Bibtex download
  • Sayers JR, Sheffield AGW & Yorks S (1999) Isolation of a novel TNF regulating protein.. ARTHRITIS AND RHEUMATISM, Vol. 42(9) (pp S201-S201) RIS download Bibtex download
  • Pickering TJ, Garforth SJ, Sayers JR & Grasby JA (1999) Mechanistic studies of a 5 ' nuclease from T5 bacteriophage. CHEMISTRY OF NUCLEIC ACID COMPONENTS, Vol. 2 (pp 161-167) RIS download Bibtex download
  • OLSEN DB & SAYERS JR (1991) PHOSPHOROTHIOATE BASED MUTAGENESIS OF SINGLE AND DOUBLE-STRANDED DNA VECTORS. SITE-DIRECTED MUTAGENESIS AND PROTEIN ENGINEERING (pp 171-179) RIS download Bibtex download
  • OLSEN DB, SAYERS JR, KOTZOREK G & ECKSTEIN F (1991) INTERACTION OF RESTRICTION ENDONUCLEASES WITH PHOSPHOROTHIOATE-CONTAINING DNA. NUCLEOSIDES & NUCLEOTIDES, Vol. 10(1-3) (pp 665-667) RIS download Bibtex download
  • ECKSTEIN F, NAKAMAYE K & SAYERS J (1987) PHOSPHOROTHIOATE-DNA FOR OLIGONUCLEOTIDE-DIRECTED MUTAGENESIS. BIOLOGICAL CHEMISTRY HOPPE-SEYLER, Vol. 368(9) (pp 1036-1036) RIS download Bibtex download

Patents

  • Sayers JR & Ross R (2009) Modified growth hormone fusion polypeptides. US7524649 B2 (USA). Appl. 28 Apr 2009. RIS download Bibtex download
  • Ross RJ, Sayers J & Artymiuk P (2009) MODIFIED GROWTH HORMONE POLYPEPTIDES. WO/2009/047474 Appl. 16 Apr 2009. RIS download Bibtex download
  • Ross RJ, Sayers J & Artymiuk P (2009) GROWTH HORMONE FUSION PROTEINS. WO/2009/013461 Appl. 29 Jan 2009. RIS download Bibtex download
  • Hulley P, Russell G & Croucher P (2006) Growth Factors. Appl. 01 Dec 2006. RIS download Bibtex download
  • Sayers JR & Duff GW () Designer proteases. US6,383,775 (USA). Appl. 01 Jan 1970. RIS download Bibtex download
  • Ross R, Artymiuk P & Sayers J () Growth hormone fusion proteins. 8,470,559 (USA). Appl. 01 Jan 1970. RIS download Bibtex download
  • Sayers JR, Ross R & Artymiuk P () Fusion protein comprising growth hormone and growth hormone receptor. 7,446,183 Appl. 01 Jan 1970. RIS download Bibtex download
  • Sayers JR, Ross R & Artymiuk P () Cytokine polypeptides and antibodies containing a signal sequence for the attachment of glycosylphosphatidylinositol. US 7,625,998 (USA). Appl. 01 Jan 1970. RIS download Bibtex download
Teaching interests

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

Professional activities

Granted patents:

  • Ross R, Artymiuk P, Sayers J. Growth hormone fusion proteins. 2013, Granted US Patent No. 8,470,559.
    (PLEASE NOTE although this has the same title and author as patent no. 8,293,709 which was already included, it is a separate patent granted in 2013).
  • Ross R, Artymiuk P, Sayers J.  Growth hormone fusion proteins. 2012, Granted US Patent No. 8,293,709.
  • Artymiuk, P, Ross R, Sayers J. Modified growth hormone polypeptides 2012, Granted US Patent No. 8,273,552.
  • Ross R, Artymiuk P, Sayers J. Fusion protein comprising growth hormone and growth hormone receptor. 2012 Granted US Patent No. 8,173,782.
  • Ross R, Sayers J, Artymiuk P.  Modified growth hormone fusion polypeptides, 2009, Granted US Patent No. 7524649.
  • 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, Artymiuk P, Sayers J. Fusion protein comprising growth hormone and growth hormone receptor. 2008 Granted US Patent No. 7,446,183.
  • Duff, G.W., Sayers, J.R., Vitovski, S. Designer proteases. 2002 Granted US Patent No.6,383,775.