Professor Tracy Palmer
Professor of Microbiology
- Email: firstname.lastname@example.org
- Telephone: +44 (0)191 208 3219
- Address: Institute for Cell and Molecular Biosciences
Centre for Bacterial Cell Biology
Faculty of Medical Sciences
Newcastle upon Tyne
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 email@example.com
Fatima Ulhuq, BBSRC-EASTBIO funded PhD Student (Media Library)
Postdoctoral Research Fellows
Dr Lisa Bowman, Wellcome Trust Postdoctoral Research Assistant (Media Library)
Dr Guillermina Casabona, Wellcome Trust Postdoctoral Research Assistant (Media Library)
Dr Jon Cherry, BBSRC Postdoctoral Research Assistant (Media Library)
Dr Chriselle Mendonca, Wellcome Trust Postdoctoral Research Assistant (Media Library)
Dr Grant Buchanan (Media Library)
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
Work in the lab is supported by the BBSRC and the Wellcome Trust
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, and Dr Phillip Stansfeld at the University of Oxford.
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.
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.
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.
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.
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 (firstname.lastname@example.org):
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.
Recent Publications (2011-2018)
Jäger F., Kneuper H., Palmer T.
EssC is a specificity determinant for Staphylococcus aureus type VII secretion.
Microbiology 2018 May; 164(5)
Casabona M.G., Kneuper H., Alferes de Lima D., Harkins C.P., Zoltner M., Hjerde E., Holden M.T.G., Palmer T.
Haem-iron plays a key role in the regulation of the Ess/type VII secretion system of Staphylococcus aureus RN6390
Microbiology 2017 Dec; 163(12)
Casabona M.G., Buchanan G., Zoltner M., Harkins C.P., Holden M.T.G., Palmer T.
Functional Analysis of the EsaB component of Staphylococcus aureus Type VII secretion system
Microbiology 2017 Nov
Habersetzer J., Moore K., Cherry J., Buchanan G., Stansfeld P.J., Palmer T.
Substrate-triggered position switching of TatA and TatB during Tat transport in Escherichia coli
Open Biology 2017 Aug; 7(8)
Huang Q., Palmer T.
Signal Peptide Hydrophobicity Modulates Interaction with the Twin-Arginine Translocase
mBio 2017 Jul-Aug; 8(4): e00909-17
Tooke F.J., Babot M., Chandra G., Buchanan G., Palmer T.
A unifying mechanism for the biogenesis of membrane proteins co-operatively integrated by the Sec and Tat pathways
elife 6:, e26577
Structural biology: Mycobacterial ESX secrets revealed
Nature Microbiology 2:, 17074Lamont CM., Kelly C.L., Pinske C., Buchanan G., Palmer T., Sargent F.
Expanding the substrates for a bacterial hydrogenlyase reaction
Microbiology 163:, 649-653
Huang Q., Alcock F., Kneuper H., Deme J.C., Rollauer S.E., Lea S.M., Berks B.C., Palmer T.
A signal sequence suppressor mutant that stabilizes an assembled state of the twin arginine translocase.
Proc Natl Acad Sci USA 114(10):, E1958 - E1967
Munnoch J.T., Widdick D.A., Chandra G., Sutcliffe I.C., Palmer T., Hutchings M.I.
Cosmid based mutagenesis causes genetic instability in Streptomyces coelicolor, as shown by targeting of the lipoprotein signal peptidase gene.
Scientific reports 6, 29495
Cao Z., Casabona M.G., Kneuper, H. Chalmers J.D., Palmer T.
The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria
Nature microbiology 2, 16183
Alcock F., Stansfeld P.J., Basit H., Habersetzer J., Baker M.A., Palmer T., Wallace M.I., Berks, B.C.
Assembling the Tat protein translocase.
Zoltner M., Ng,W.M., Money J.J., Fyfe P.K., Kneuper H., Palmer T., Hunter W.N.
EssC: domain structures inform on the elusive translocation channel in the Type VII secretion system.
The Biochemical Journal 473, 1941-1952
Parthasarathy S., Parapatla H., Nandavaram A., Palmer T., Siddavattam, D.
Organophosphate Hydrolase Is a Lipoprotein and Interacts with Pi-specific Transport System to Facilitate Growth of Brevundimonas diminuta Using OP Insecticide as Source of Phosphate.
The Journal of Biological Chemistry 291, 7774-7785
B. Warne, C.P. Harkins, S.R. Harris, A. Vatsiou, N. Stanley-Wall, J. Parkhill, S.J. Peacock, T. Palmer, M. T. G. Holden
The Ess/Type VII secretion system of Staphylococcus aureus shows unexpected genetic diversity
BMC Genomics 17: 222
F. Jager, M. Zoltner, H. Kneuper, W.N. Hunter, T. Palmer
Membrane interactions and self-association of components of the Ess/Type VII secretion sytem of Staphylococcus aureus
FEBs Letters 590: 349-57
C.L. Kelly, C. Pinske, B.J. Murphy, A. Parkin, F. Armstrong, T. Palmer, F. Sargent
Integration of an [FeFe]-hydrogenase into the anaerobic metabolism of Escherichia coli
Biotechnology Reports 8: 94-104
J.S. McDowall, M.C. Hjersing, T. Palmer, F. Sargent
Dissection and engineering of the Escherichia coli formate hydrogenlyase complex
FEBS Letters 589:3141-3147
F. Cleon, J. Habersetzer, F. Alcock, H. Kneuper, P.J. Stansfeld, H. Basit, M.I. Wallace, B.C.Berks, T. Palmer
The TatC component of the twin-arginine protein translocase functions as an obligate oligomer
Molecular Microbiology 98: 111-129
D.F. Browning, V.N. Bavro, J.L. Mason, Y.R. Sevastsyanovich, A.E. Rossiter, M. Jeeves, T.J. Wells, T.J. Knowles, A.F. Cunningham, J.W. Donald, T. Palmer, M. Overduin, I.R. Henderson
Cross-species chimeras reveal BamA POTRA and B-barrel domains must be fine-tuned for efficient OMP insertion
Molecular Microbiology 97: 646-659
J.J. Hamilton, V.L. Marlow, R.A.Owen, A. Mde. Costa, M. Guo, G. Buchanan, G. Chandra, M. Trost, S.J. Coulthurst, T. Palmer, N.R. Stanley-wall, F. Sargent
A holin and an endopeptidase are essential for chitinolytic protein secretion in Serratia marcescens
Journal of Cell Biology 207:615-626
J.S McDowall, B.J.Murphy, M. Haumann, T.Palmer, F.A. Armstrong, F. Sargent
Bacterial formate hydrogenlyase complex
Proc Natl Acad Sci USA 111: 3948-3956
H. Kneuper, Z.P. Cao, K.B. Twomey, M. Zoltner, F. Jager, J.S. Cargill, J. Chalmers, M.M. Van der Kooi-Pol, J.M. van Dijl, R.P. Ryan, W.N. Hunter, T. Palmer
Heterogeneity in ess transcriptional organization and variable contribution of the Ess/Type VII protein secretion system to virulence across closely related Staphylococcus aureus strains
Molecular Microbiology 93: 928-943
J. M. Dow, S. Grahl, R. Ward, R. Evans, O. Byron, D. G. Norman, T. Palmer and F. Sargent
Characterization of a periplasmic nitrate reductase in complex with its biosynthetic chaperone
The FEBS Journal 281: 246-260
A. P. Hopkins, G. Buchanan and T. Palmer
The role of the twin arginine protein transport pathway in the assembly of the Streptomyces coelicolor A3(2) cytochrome bc1 complex
Journal of Bacteriology 196: 50-59
L. Bowman, T. Palmer, and F. Sargent
A regulatory domain controls the transport activity of a twin-arginine signal peptide
FEBS Letters 587: 3365-70
F. Sargent, F. A. Davidson, C. L. Kelly, R. Binny, N. Christodoulides, D. Gibson, E. Johansson, K. Kozyrska, L. Licandro Lado, J. MacCallum, R. Montague, B. Ortmann, R. Owen, S. J. Coulthurst, L. Dupuy, A. R. Prescott and T. Palmer
A synthetic system for expression of components of a bacterial microcompartment
Microbiology 159: 2427-2436
M. J. James, S. J. Coulthurst, T. Palmer and F. Sargent
Signal peptide etiquette during assembly of a complex respiratory enzyme
Molecular Microbiology 90: 400-414
F. Alcock, M. A. B. Baker, N. P. Greene, T. Palmer, M. I. Wallace and B. C. Berks
Live cell imaging shows reversible assembly of the TatA component of the twin-arginine protein transport system
Proceedings of the National Academy of Sciences of the USA 110: E3650-9
J. M. Dow, F. Gabel, F. Sargent and T. Palmer
Characterization of a pre-export enzyme-chaperone complex on the twin-arginine transport pathway
Biochemical Journal 452: 57-66
M. Zoltner, D. G. Norman, P. K. Fyfe, H. El Mkami, T. Palmer and W. N. Hunter
The architecture of EssB, an integral membrane component of the type VII secretion system
Structure 21: 595-603
M. Zoltner, P. K. Fyfe, T. Palmer and W. N. Hunter
Characterization of Staphylococcus aureus EssB, an integral membrane component of the Type VII secretion system: atomic resolution crystal structure of the cytoplasmic segment
Biochemical Journal 449: 469-477
J. K. Fyans, D. Bignell, R. Loria, I. Toth and T. Palmer
The ESX/Type VII secretion system modulates development but not virulence of the plant pathogen Streptomyces scabies
Molecular Plant Pathology 14: 119-130
S. E. Rollauer, M. J. Tarry, J. E. Graham, M. Jääskeläinen, F. Jäger, S. Johnson, M. Krehenbrink, S.-M. Liu, M. J. Lukey, J. Marcoux, M. A. McDowell, F. Rodriguez, P. Roversi, P. J. Stansfeld, C. V. Robinson, M. S. P. Sansom, T. Palmer, M. Högbom, B. C. Berks and S. M. Lea
Structure of the TatC core of the twin arginine protein transport system
Nature 492: 210-214
J. Willemse, B. Ruban-Osmialowska, D. Widdick, K. Celler, M. I. Hutchings, G. P. van Wezel and T. Palmer
Dynamic localization of Tat protein transport machinery components in Streptomyces coelicolor
Journal of Bacteriology 194: 6272-6281
R. Keller, J. de Keyzer, A. J. M. Driessen and T. Palmer
Co-operation between different targeting pathways during integration of a membrane protein
Journal of Cell Biology 199: 303-315
H. Kneuper, B. Maldonado, F. Jäger, M. Krehenbrink, G. Buchanan, R. Keller, M. Müller, B. C. Berks and T. Palmer>
Molecular dissection of TatC defines critical regions essential for protein transport and a TatB-TatC contact site
Molecular Microbiology 85: 945-961
T. Palmer and B. C. Berks
The twin-arginine translocation (Tat) protein export pathway
Nature Reviews Microbiology 10: 483-496
M. J. Fritsch, M. Krehenbrink, M. J. Tarry, B. C. Berks and T. Palmer
Processing by rhomboid protease is required for Providentia stuartii TatA to interact with TatC and to form functional homo-oligomeric complexes
Molecular Microbiology 84: 1108-1123
S. Koch, M. J. Fritsch, G. Buchanan and T. Palmer
The Escherichia coli TatA and TatB proteins have an N-out C-in topology in intact cells
Journal of Biological Chemistry 287: 14420-14431
A. Parkin, L. Bowman, M. M. Roessler, R. A. Davies, T. Palmer, F. A. Armstrong and F. Sargent
How Salmonella oxidises H(2) under aerobic conditions
FEBS Letters 586: 536-544
J. Bauer, M. J. Fritsch, T. Palmer, G. Unden
Topology and accessibility of the transmembrane helices and the sensory site in the bifunctional transporter DcuB of Escherichia coli
Biochemistry, 50: 5925-5938
B. Maldonado, H. Kneuper, G. Buchanan, K. Hatzixanthis, F. Sargent, B. C. Berks, T. Palmer
Genetic evidence for a TatC dimer at the core of the Escherichia coli twin arginine (Tat) protein translocase
Journal of Molecular Microbiology and Biotechnology. 20(3): 168-175
B. Maldonado, G. Buchanan, M. Müller, B. C. Berks, T. Palmer
Characterisation of the membrane-extrinsic domain of the TatB component of the twin arginine protein translocase
FEBS letters. 585: 478-484
T. Palmer, F. Sargent, B. C. Berks
The Tat protein export pathway.
In Ecosal Plus - Escherichia coli and Salmonella: Cellular and Molecular Biology
D. A. Widdick, M. G. Hicks, B. J. Thompson, A. Tschumi, G. Chandra, I. C. Sutcliffe, J. K. Brülle, P. Sander, T. Palmer, M. I. Hutchings
Dissecting the complete lipoprotein biogenesis pathway in Streptomyces scabies.
Molecular Microbiology. 80: 1395-1412