Jon R Sayers
COVID19 Update Over the last 16 months my laboratory has produced large quantities of highly purified, recombinant SAR-CoV-2 Nucleocapsid protein for use in quantitative ELISAs, research and seroprevalence studies. See https://doi.org/10.12688/wellcomeopenres.17143.1
TEACHING: I teach graduate-level biochemistry, molecular & structural biology, bioinformatics and biotechnology in relation to biomedical research and drug discovery. See our Masters pathways in:
Microbial Pathogenicity; http://www.shef.ac.uk/medicine/molmed/structure/micropath
Genetic Basis of Disease;
http://www.shef.ac.uk/medicine/molmed/structure/genetics
and Experimental Medicine (also known as Translational Medicine);
http://www.shef.ac.uk/medicine/molmed/structure/experimental
RESEARCH INTERESTS: My group carries out research on the molecular basis of host-pathogen interactions, fundamental molecular microbiology relating to DNA repair and gene expression, and in biotechnology. We work on bacteria causing diseases such as meningitis, gonorrhoea, chronic bronchitis and septicaemia. In 2013, I was elected to a Fellowship of the Society of Biology.
The group is involved in four main areas:
* Molecular mechanisms involved in protein:DNA interactions.
* Secreted microbial proteins, pathogenesis and the host response.
* Novel applications of biotechnology to biomedical research and drug development.
* Structure-based drug design.
Examples of current projects;
The Mexican government sponsor a CONACyt PhD student in my laboratory studying flap endonucleases. An EU Horizon 2020 Marie Curie Individual Research Fellow is studying inhibitors of kinetoplastid flap endonucleases as potential treatments for neglected tropical diseases.
Mechanistic Studies on Flap Endonuclease (5'-3' Exonuclease or 5' Nuclease) See http://www.sayers.staff.shef.ac.uk/fen/
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. Our work has been funded by the BBSRC, The Wellcome Trust, Medical Research Council, Bill & Melinda Gates Foundation, DeFENition Ltd and the White Roses Consortium amongst others.
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 recognise their target sequences should provide new insights into molecular recognition processes.
Significance of IgA1 Proteases in Pathogenic Neisseria meningitidis and Haemophilus influenzae. (http://www.sayers.staff.shef.ac.uk/igap/)
We have discovered a strong link between carriage of gene containing a highly variable domain and pathogenesis in these two meningitis-causing organisms. 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.
TRANSLATIONAL MEDICINE: Engineering cytokines as novel therapeutic agents. In 2001 I become a director and co-founder of Asterion Ltd., a biotech. spin-off company. The company has six granted US patents and many others in the pipeline. I also have patent application in the area of vaccine development against human and animal bacterial infections. I founded DeFENition Ltd in 2016, a spin-out developing new antibiotics against a novel protein target.
Studying /Researching with us. Please contact me should be interesting in applying for training fellowships or studying for a PhD with us.
Phone: +44 114 271 3027
Address: University of Sheffield Medical School
Florey Institute for Host Pathogen Interactions
Dept. of Infection & Immunity
Sheffield, S10 2RX, UK
TEACHING: I teach graduate-level biochemistry, molecular & structural biology, bioinformatics and biotechnology in relation to biomedical research and drug discovery. See our Masters pathways in:
Microbial Pathogenicity; http://www.shef.ac.uk/medicine/molmed/structure/micropath
Genetic Basis of Disease;
http://www.shef.ac.uk/medicine/molmed/structure/genetics
and Experimental Medicine (also known as Translational Medicine);
http://www.shef.ac.uk/medicine/molmed/structure/experimental
RESEARCH INTERESTS: My group carries out research on the molecular basis of host-pathogen interactions, fundamental molecular microbiology relating to DNA repair and gene expression, and in biotechnology. We work on bacteria causing diseases such as meningitis, gonorrhoea, chronic bronchitis and septicaemia. In 2013, I was elected to a Fellowship of the Society of Biology.
The group is involved in four main areas:
* Molecular mechanisms involved in protein:DNA interactions.
* Secreted microbial proteins, pathogenesis and the host response.
* Novel applications of biotechnology to biomedical research and drug development.
* Structure-based drug design.
Examples of current projects;
The Mexican government sponsor a CONACyt PhD student in my laboratory studying flap endonucleases. An EU Horizon 2020 Marie Curie Individual Research Fellow is studying inhibitors of kinetoplastid flap endonucleases as potential treatments for neglected tropical diseases.
Mechanistic Studies on Flap Endonuclease (5'-3' Exonuclease or 5' Nuclease) See http://www.sayers.staff.shef.ac.uk/fen/
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. Our work has been funded by the BBSRC, The Wellcome Trust, Medical Research Council, Bill & Melinda Gates Foundation, DeFENition Ltd and the White Roses Consortium amongst others.
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 recognise their target sequences should provide new insights into molecular recognition processes.
Significance of IgA1 Proteases in Pathogenic Neisseria meningitidis and Haemophilus influenzae. (http://www.sayers.staff.shef.ac.uk/igap/)
We have discovered a strong link between carriage of gene containing a highly variable domain and pathogenesis in these two meningitis-causing organisms. 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.
TRANSLATIONAL MEDICINE: Engineering cytokines as novel therapeutic agents. In 2001 I become a director and co-founder of Asterion Ltd., a biotech. spin-off company. The company has six granted US patents and many others in the pipeline. I also have patent application in the area of vaccine development against human and animal bacterial infections. I founded DeFENition Ltd in 2016, a spin-out developing new antibiotics against a novel protein target.
Studying /Researching with us. Please contact me should be interesting in applying for training fellowships or studying for a PhD with us.
Phone: +44 114 271 3027
Address: University of Sheffield Medical School
Florey Institute for Host Pathogen Interactions
Dept. of Infection & Immunity
Sheffield, S10 2RX, UK
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Papers by Jon R Sayers
The Experimental Medicine pathway is intended for students who are interested in the process and the practicalities of investigating human diseases and designing therapies.
MED6024 "Laboratory Project/Experimental Medicine Pathway" (60 credit) introduces you to doing science; working on your own project, with supervision, in a research laboratory.
MED6020 “Molecular and Cellular Basis of Diseases” (10 credit) illustrates with recent examples how you can now investigate important molecular changes that occur in disease states and investigate their significance in pathogenesis.
MED6021 “Model Systems in Medical Research” (10 credit) teaches you by example how disease processes are modelled in appropriate systems.
MED6022 “Novel Therapies” (10 credit) introduces you to how novel therapeutic strategies are translated from experimental models into marketable treatments.
MED6023 “Project Presentation/Experimental Medicine Pathway” (10 credit) teaches you how to be involved in a scientific meeting, make a presentation and organise a description of your pathway-appropriate project.
MED6024 “Laboratory Project/Experimental Medicine Pathway” (60 credit) introduces you to doing science; working on your own project, with supervision, in a research laboratory. See links below:"
The taught "pathways" programmes run from late January until mid-March. This is followed by a "Project Presentation" module and five-month Laboratory Project module. These two modules will be appropriate to your choice of pathway.
The Genetic Mechanisms pathway is intended for students who are interested in the basic concepts and bio-informatics tools used to interpret genomic information (sequences) for understanding biological function (structure, phenotype, disease) and designing drugs. It consists of the following modules:
MED6070 “Modelling Interactions of Proteins” (15 credit) teaches the analytical and practical skills to understand how proteins function through their interactions with other gene products and how drugs are designed to interfere specifically with certain interactions and not others.
MED6071 “Gene Function, Models and Network” (15 credit) focuses on the theories and software tools for understanding the regulatory mechanisms that control the expression and function of genes, both individually and as component of co-ordinated gene networks.
MED6073 “Project Presentation/Genetics Pathway” (10 credit) teaches you how to be involved in a scientific meeting, make a presentation and organise a description of your pathway-appropriate project.
MED6074 “Laboratory Project/Genetics Pathway” (60 credit) introduces you to doing science; working on your own project, with supervision, in a research laboratory.