Centre for Bacterial Cell Biology

Staff Profile

Professor Tracy Palmer

Professor of Microbiology

Background

Vacancies

We are always open to informal enquiries for PhD or Post-Doctoral positions in this lab, and often find a way to fund good candidates. Please feel free to email me if you are interested tracy.palmer@ncl.ac.uk


Graduate Students

Fatima Ulhuq, BBSRC-EASTBIO-funded PhD student 

Jose Gallego, Faculty-funded PhD student

Ellie Boardman, Faculty-funded PhD student

Stephen Garrett, NLD BBSRC-funded PhD student

Postdoctoral Research Fellows

Dr Felicity Alcock, BBSRC-funded Postdoctoral Research Assistant

Dr Lisa Bowman, Wellcome Trust-funded Postdoctoral Research Assistant

Dr Jon Cherry, BBSRC-funded Postdoctoral Research Assistant

Dr Chriselle Mendonca, Wellcome Trust-funded Postdoctoral Research Assistant

Dr Emmanuele Severi, MRC-funded Postdoctoral Research Assistant


Scientific Officer

Dr Grant Buchanan


Education and Training

2018- Professor of Microbiology, Institute for Cell and Molecular Biosciences, Centre for Bacterial Cell Biology, Newcastle University

2017-2018 Professor of Molecular Microbiology, School of Life Sciences, University of Dundee

2007-2017 - Professor of Molecular Microbiology, Head of the Division of Molecular Microbiology, School of Life Sciences, University of Dundee

2004-2007 - MRC Senior Non Clinical Research Fellow based at John Innes Centre, Norwich

1996-2004 - Royal Society University Research Fellow based at John Innes Centre, Norwich

1993-1996 - University Research Fellow, Department of Biochemistry, University of Dundee

1992-1993 - Postdoctoral Research Assistant, University of Dundee with Prof D.H. Boxer

1988-1991 - Research Associate (RA1B) and PhD student, University of Birmingham with Prof J.B. Jackson

1988-1991 - Postgraduate: Ph.D. Biochemistry, University of Birmingham

1985-1988 - Undergraduate: B.Sc. Biochemistry (First Class Honours), University of Birmingham


Distinctions and Awards

2018 - Elected Fellow of the Royal Society (FRS)

2017- Elected Member of the European Molecular Biology Organisation

2015 - Elected Member of the European Academy of Microbiology

2015 - Elected Fellow of the American Academy of Microbiology

2011-2016 - Royal Society/Wolfson Merit Award Holder

2010 - Elected Fellow of the Society of Biology (FRSB)

2009 - Elected Fellow of the Royal Society of Edinburgh (FRSE)

2004-2009 - Medical Research Council Senior Non Clinical Fellowship

2002 - The Microbiology Society Fleming Medal

1996-2004 - Royal Society University Research Fellowship

Funding

Work in the lab is supported by the BBSRC, MRC and the Wellcome Trust






Research

Research Interests

The twin arginine protein transport (Tat) pathway

The Tat protein export system is present in the cytoplasmic membranes of many bacteria and archaea and is also found in the mitochondria and chloroplasts of plants. It has the highly unusual feature of transporting fully folded proteins. Substrates are targeted to the Tat machinery because they are synthesized with N-terminal signal peptides that contain a conserved and essential twin-arginine motif. We are interested in the mechanism of substrate recognition and protein translocation by the Tat pathway in the model organism Escherichia coli. Much of our work on the Tat pathway is undertaken in collaboration with Professors Ben Berks and Susan Lea (University of Oxford) and Dr Phillip Stansfeld (University of Warwick).

The Tat system has a challenging task because it allows the passage of folded substrates of varying sizes while maintaining the impermeability of the membrane to ions. The key components of the E. coli Tat system are three small membrane proteins termed TatA, TatB and TatC. A schematic for the dynamic operation of the Tat pathway is given in Fig 1.

(Fig 1 - Media Library)

We are interested in the organisation of the TatABC receptor complex and the rearrangements that occur upon signal peptide interaction, and take a range of approaches including genetics and in vivo crosslinking analysis to probe these events. Recently we have used disulphide mapping and molecular modelling (with Dr Phillip Stansfeld) to identify the positions of TatA and TatB within the receptor complex in resting state in vivo, and to assess how these change when a substrate is bound. This has allowed us to generate a model for the resting state TatABC complex shown in Fig 2.

(Fig 2 - Media Library)


The Type VII protein secretion pathway

The Type VII secretion system (T7SS) is found primarily in Gram positive bacteria and we study it in the opportunistic human pathogen Staphylococcus aureus. We collaborate with Prof Bill Hunter (School of Life Sciences, University of Dundee) to examine the structure and function of the core components of the secretion machinery (Fig 3) and the mechanism of substrate recognition.

(Fig 3 - Media Library)

We are also interested in T7SS substrate proteins, collaborating with Prof Matthias Trost (Newcastle University) to undertake proteomic identification of secreted effectors. We have identified a secreted nuclease substrate of the T7SS, EsaD, which inhibits the growth of closely related strains (Fig 4). EsaD interacts with two accessory proteins encoded at the T7SS gene cluster, EsaG, a neutralising antitoxin, and EsaE, a putative chaperone that is required for EsaD secretion. Our results have demonstrated that the T7SS has anti-bacterial activity in addition to anti-eukaryotic function.

(Fig 4- Media Library)


Molybdenum Cofactor Mutant Strains


We have the following E. coli strains/plasmids freely available to the molybdenum/ tungsten enzyme community. If you require any of these please send an e-mail either to myself or Dr Grant Buchanan (grant.buchanan@ncl.ac.uk):

TP1000 (As MC4100 ΔmobAB::Kan) published in Palmer et al. (1996) Mol. Microbiol. 20, 875-884. Useful for expressing eukaryotic molybdoenzymes since it does not make the guanine dinucleotide form of the cofactor, instead accumulates MPT. Already used as standard by several groups.

TP1001 (As MC4100 ΔmobA, unmarked mutation). Unpublished. Exactly same strain background as TP1000 but has no antibiotic marker and therefore is useful if you wish to use kanamycin resistant plasmids.

TP1004 (As RK4353 ΔmobAB::Kan). Unpublished. Similar to TP1000 but in a slightly different strain background that may synthesise more moco.

TP1005 (As P4X ΔmobAB::Kan). Unpublished. Strain background, P4X is a methionine auxotroph and therefore is useful for selenomethionine substitution of proteins for crystallographic work. P4X is a much more 'wild type' strain of E. coli and anecdotally has much higher levels of native Mo-enzyme activity than many  'tamer' lab strains.

TP1010 (As BL21(DE3) ΔmobAB::Kan). Unpublished. mob mutant in the BL21 strain. Useful if you wish to express genes under control of the T7 phage promoter. However, be cautious, our experience suggests that BL21 is not a good host strain since its levels of native Mo-enzyme activity are very low.

TP1017 (As JM101 ΔmobAB::Kan). Unpublished. mob mutant in the JM101 background. JM101 has chromosomal lacIq and is therefore a useful strain if you wish to express from any lac-controlled promoter (often present on many standard expression vectors).

Plasmid pTPR1. Unpublished. A medium copy number plasmid (based on pRK415) specifying tetracycline resistance. Carries a 5.9kb fragment of E. coli DNA covering the moa genes. Might be useful to boost MPT synthesis.


Publications