Education and qualifications:
10/1996 – 11/2000 D.Phil. (Physiological Sciences) at Sir William Dunn School of Pathology, University of Oxford, Supervisor: Prof. J. Errington
10/1986 – 07/1989 BSc with Hons. (Bacteriology and Molecular Genetics) University of Bristol,
Part II Supervisor: Dr. J Grinsted
2010 - Senior Lecturer, Centre for Bacterial Cell Biology Newcastle University
2006 - 2009 Lecturer, ICaMB, University of Newcastle
2004 – 2006 University Research Lecturer, Sir William Dunn School of Pathology, Oxford University
2000 – 2006 Consultant, Prolysis Ltd, Oxford
2000 – 2004 Senior Research
assistant (RS II), Sir William Dunn School of Pathology, Oxford
1990 - 1999 Research Assistant, Sir William Dunn School of Pathology, Oxford University
1989 – 1990 Medical Laboratory
Scientific Officer, Dept. of Paediatrics, John Radcliffe Hospital,
BBSRC Peer review panel BBSRC Committee B: Plants, Microbes, Food and Sustainability panel since 2012
Management of the CBCB Microscopy facility.
Member of the Bio Imaging committee for the Medical Faculty
Member of the Robotics committee for the Medical Faculty
Karzan Sidiq - (international funding)
Jad Sassine - (MC studentship - AMBER project)
Man Chow - (Self funded)
Gabriella Henriques (MC visiting fellowship)
A bacterial cell as a gross simplification is sometimes described as a collection of enzymes and nucleic acid enclosed in a lipid bag. In reality this is far from the truth, the bacterial cell has levels of organisation and complexity comparable to higher organisms, but due the difference in scale these properties were invisible. Recent advances in imaging techniques are just beginning to reveal these complexities that at almost at the limit of resolution for light microscopy and invisible to electron microscopy. Characterising and understanding the processes that generate and maintain this organisation represents the next challenge.
Research in this lab predominantly utilises the Gram-positive bacterium Bacillus subtilis as a model system, but may also use Listeria spp. Corynebacterium glutamicum, Staph. aureus and Strep. pneumonia for comparison due to their interesting morphological diversity. To support this work we are able to utilise a wide range of techniques most of which are available in the Centre.
Currently the main areas of research are focused on:-
The physical properties of the cell envelope of Bacillus subtilis:
The interface the bacterial cell and its environment has an intricate role in biology. It must permit the selective passage of material too and from the cell membrane, but be structurally robust enough to prevent osmotic lysis of the cell, the entry of large toxic molecules and repel the attacks of enzymes and bacteriophages. However it must also be capable for dynamic remodelling to allow the enlargement and division of the cell. Thus an understanding of the composition of the cell wall and the roles of the individual components is critical.
Determination of the composition of the cell wall and how it changes according to the phase of growth or environmental conditions. (K. Sidiq)
Design and characterisation of probes to investigate the bacterial cell wall and its basic physical properties as extracted sacculi as well as in vivo. (Man Chow)
Bacterial cell wall biosynthesis:
Bacterial cell wall helps to maintain cell shape but most importantly it provides protection to the cells, and has been one of the targets for antibiotics. However, the mechanisms involved in cell wall biosynthesis are still poorly understood. Most of the analysis has been restricted to either the biosynthetic pathway required for synthesis of the major cell wall precursors (e.g. mur or mra genes) or the final steps of peptidoglycan synthesis (carried out by penicillin-binding proteins). Very little is known about the intermediate steps whereby the precursors are exported from the cytoplasm to the outside of the cell and incorporated into the existing structure to allow cell enlargement or division. Recent studies have provided evidence for specific complexes, (cytoskeletal structures) central to these events. However, the mechanism and the functional components of these complexes have yet to be clearly defined. Thus, there are many areas to explore, including peptidoglycan precursor export and incorporation, cell wall maturation and degradation, secondary polymer biosynthesis, export and incorporation (e.g. teichoic acids).
Defining the roles of specific PBPs in peptidoglycan synthesis and maturation (A. Guyet)
Constructing strains with the minimum complement of enzymes necessary for normal growth and division (A. Bone and G. Henriques)
Understanding the mechanisms that coordinate peptidoglycan synthesis and degradation, to allow controlled growth and division (A. Guyet)
Determination of antibiotic resistance determinants and their mode of action - primarily focusing on wall active compounds (K. Sidiq)
Biological role of membrane proteins
Following on form the "omic" revolutions, we now have a vast data base of genes that are present in bacteria, but a limited understanding of their biological function. One sub class of proteins that are generally very variable are the membrane spanning proteins, many of which are annotated with potential functions, but not definitive experimental data supports these predictions. To correct this gap in our understanding we are looking at systematic methods to identify the functions of this sub set of proteins using classical genetic techniques combined with robotics. This work is designed to aid the development of the minimal genome by defining genes that are either redundant in function or are unnecessary except under specific condition.
The ultimate objective being the construction of strains with the minimal gene content for viable replication that can be customised with a specific gene complement (set of bio-bricks) to fulfil a specific function.
High throughput genetic manipulation of strains using various selection systems and screening methods for phenotypic characterisation (G. Henriques)
MIC2028 Practical Skills in Medical Microbiology Practical Supervisor
MIC3044 Integrated Microbiology and Immunology Lecturer
MMB8008 Cell Cycle Control and Cell Signalling in Health and Disease Lecturer
Pastoral Tutor for undergraduates in years 1, 2 and 3.
Undergraduate project supervisor
MRes and MSci project supervisor
M. Phil supervisor for M. Chow (2014).
PhD supervisor for M. Xu ( D.Phil in Oxford 2008), P. Gamba (2011), A. Doble (2012), S. Moore (2013), K Sidiq (2012-2015), and Jad Sassine (2013-2016).