Staff Profile

I am a member of the Biosciences Institute and my work contributes to the Microbes in Health and Disease Theme

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

Stephen Garrett, NLD BBSRC-funded PhD student

Kieran Bowran, Faculty-funded PhD student

Yaping Yang, China Scholarship Council-funded PhD student

Andrew Higginson, NLD BBSRC-funded PhD student

Eunice Lee, Faculty-funded PhD student

Postdoctoral Research Fellows

Dr Felicity Alcock, Wellcome-funded Postdoctoral Research Assistant

Dr Ellie Boardman, Wellcome-funded Postdoctoral Research Assistant

Dr Merel Damen, Wellcome-funded Research Assistant 

Dr Nicole Mietrach, DFG-funded Postdoctoral Fellow

Dr Emmanuele Severi, Wellcome-funded Postdoctoral Research Assistant

Dr Amy Tooke Wellcome-funded Research Assistant 

Education and Training

2018- Professor of Microbiology, Microbes in Health and Disease Theme, Cookson Building 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

2021 - Elected Fellow of the Academy of Medical Sciences

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, Wellcome, Newcastle University and the China Scholarship Council.

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 me an e-mail (tracy.palmer@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 lacI^q 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.

• Articles

  • Bowran K, Garrett SR, van Vliet AHM, Palmer T. A novel variant of the Listeria monocytogenes type VII secretion system EssC component is associated with an Rhs toxin. Microbial Genomics 2023, 9(6), 001036.
  • Kaderabkova N, Bharathwaj M, Furniss RCD, Gonzalez D, Palmer T, Mavridou DAI. The biogenesis of β-lactamase enzymes. Microbiology 2022, 168(8), 001217.
  • Garrett SR, Mariano G, Dicks J, Palmer T. Homologous recombination between tandem paralogues drives evolution of a subset of type VII secretion system immunity genes in firmicute bacteria. Microbial Genomics 2022, 8(8), 000868.
  • Bharathwaj M, Webb CT, Vadlamani G, Stubenrauch CJ, Palmer T, Lithgow T. The Carbapenemase BKC-1 from Klebsiella pneumoniae Is Adapted for Translocation by Both the Tat and Sec Translocons. mBio 2021, 12(3), e01302-21.
  • Severi E, Rudden M, Bell A, Palmer T, Juge N, Thomas GH. Multiple evolutionary origins reflect the importance of sialic acid transporters in the colonization potential of bacterial pathogens and commensals. Microbial Genomics 2021, 7(6), 000614.
  • Bowran K, Palmer T. Extreme genetic diversity in the type VII secretion system of Listeria monocytogenes suggests a role in bacterial antagonism. Microbiology 2021, 167(3), 001034.
  • Alcock F, Palmer T. Activation of a bacterial killing machine. PLoS Genetics 2021, 17, e1009261.
  • Passmore IJ, Coll F, Dow JM, Cuccui J, Palmer T, Wren BW. The ferric citrate regulator, FecR, is translocated across the bacterial inner membrane via a unique Twin-arginine transport dependent mechanism. Journal of Bacteriology 2020, 202, e00541-19.
  • Finney AJ, Buchanan G, Palmer T, Coulthurst SJ, Sargent F. Activation of a [nife]-hydrogenase-4 isoenzyme by maturation proteases. Microbiology 2020, 166(9), 854-860.
  • Ulhuq FR, Gomes MC, Duggan G, Guo M, Mendonca C, Buchanan G, Chalmers JD, Cao Z, Kneuper H, Murdoch S, Thomson S, Strahl H, Trost M, Mostowy S, Palmer T. A membrane-depolarizing toxin substrate of the Staphylococcus aureus Type VII secretion system mediates intra-species competition. Proceedings of the National Academy of Sciences of the United States of America 2020, 117(34), 20836-20847.
  • Costa MAA, Owen RA, Tammsalu T, Buchanan G, Palmer T, Sargent F. Controlling and co-ordinating chitinase secretion in a Serratia marcescens population. Microbiology 2019, 165(11), 1233-1244.
  • Petru M, Wideman J, Moore K, Alcock F, Palmer T, Dolezal P. Evolution of mitochondrial TAT translocases illustrates the loss of bacterial protein transport machines in mitochondria. BMC Biology 2018, 16, 141.
  • Jager F, Kneuper H, Palmer T. EssC is a specificity determinant for Staphylococcus aureus type VII secretion. Microbiology 2018, 164(5), 816-820.
  • Cao Z, Casabona MG, Kneuper H, Chalmers JD, Palmer T. The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria. Nature Microbiology 2017, 2(1), 16183.
  • Habersetzer J, Moore K, Cherry J, Buchanan G, Stansfeld PJ, Palmer T. Substrate-triggered position switching of TatA and TatB during Tat transport in Escherichia coli. Open Biology 2017, 7(8), 170091.
  • Palmer T. Structural biology: Mycobacterial ESX secrets revealed. Nature Microbiology 2017, 2, 17074.
  • Huang Q, Palmer T. Signal peptide hydrophobicity modulates interaction with the Twin-Arginine translocase. mBio 2017, 8(4), e00909-17.
  • Casabona MG, Kneuper H, de Lima DA, Harkins CP, Zoltner M, Hjerde E, Holden MTG, Palmer T. Haem-iron plays a key role in the regulation of the Ess/type VII secretion system of Staphylococcus aureus RN6390. Microbiology 2017, 163(12), 1839-1850.
  • Casabona MG, Buchanan G, Zoltner M, Harkins CP, Holden MTG, Palmer T. Functional analysis of the EsaB component of the Staphylococcus aureus type VII secretion system. Microbiology 2017, 163(12), 1851-1863.
  • Lamont CM, Kelly CL, Pinske C, Buchanan G, Palmer T, Sargent F. Expanding the substrates for a bacterial hydrogenlyase reaction. Microbiology 2017, 163(5), 649-653.
  • Tooke FJ, 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 2017, 6, e26577.
  • Huang Q, Alcock F, Kneuper H, Deme JC, Rollauer SE, Lea SM, Berks BC, Palmer T. A signal sequence suppressor mutant that stabilizes an assembled state of the twin arginine translocase. Proceedings of the National Academy of Sciences of the United States of America 2017, 114(10), E1958-E1967.
  • Warne B, Harkins CP, Harris SR, Vatsiou A, Stanley-Wall N, Parkhill J, Peacock SJ, Palmer T, Holden MTG. The Ess/Type VII secretion system of Staphylococcus aureus shows unexpected genetic diversity. BMC Genomics 2016, 17, 222.
  • Palmer T. Spotlight on... Tracy Palmer. FEMS Microbiology Letters 2016, 363(24), fnw271.
  • 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. Journal of Biological Chemistry 2016, 291(14), 7774-7785.
  • Jager F, Zoltner M, Kneuper H, Hunter WN, Palmer T. Membrane interactions and self-association of components of the Ess/Type VII secretion system of Staphylococcus aureus. FEBS Letters 2016, 590(3), 349-357.
  • Zoltner M, Ng WMAV, Money JJ, Fyfe PK, Kneuper H, Palmer T, Hunter WN. EssC: Domain structures inform on the elusive translocation channel in the Type VII secretion system. Biochemical Journal 2016, 473(13), 1941-1952.
  • Munnoch JT, Widdick DA, Chandra G, Sutcliffe IC, Palmer T, Hutchings MI. Cosmid based mutagenesis causes genetic instability in Streptomyces coelicolor, as shown by targeting of the lipoprotein signal peptidase gene. Scientific Reports 2016, 6, 29495.
  • Alcock F, Stansfeld PJ, Basit H, Habersetzer J, Baker MA, Palmer T, Wallace MI, Berks BC. Assembling the Tat protein translocase. eLife 2016, 5, e20718.
  • Cleon F, Habersetzer J, Alcock F, Kneuper H, Stansfeld PJ, Basit H, Wallace MI, Berks BC, Palmer T. The TatC component of the twin-arginine protein translocase functions as an obligate oligomer. Molecular Microbiology 2015, 98(1), 111-129.
  • Kelly CL, Pinske C, Murphy BJ, Parkin A, Armstrong F, Palmer T, Sargent F. Integration of an [FeFe]-hydrogenase into the anaerobic metabolism of Escherichia coli. Biotechnology Reports 2015, 8, 94-104.
  • McDowall JS, Hjersing MC, Palmer T, Sargent F. Dissection and engineering of the Escherichia coli formate hydrogenlyase complex. FEBS Letters 2015, 589(20), 3141-3147.
  • Browning DF, Bavro VN, Mason JL, Sevastsyanovich YR, Rossiter AE, Jeeves M, Wells TJ, Knowles TJ, Cunningham AF, Donald JW, Palmer T, Overduin M, Henderson IR. Cross-species chimeras reveal BamA POTRA and β-barrel domains must be fine-tuned for efficient OMP insertion. Molecular Microbiology 2015, 97(4), 646-659.
  • Hopkins A, Buchanan G, Palmer T. Role of the twin arginine protein transport pathway in the assembly of the Streptomyces coelicolor cytochrome bc₁ complex. Journal of Bacteriology 2014, 196(1), 50-59.
  • Kneuper H, Cao ZP, Twomey KB, Zoltner M, Jager F, Cargill JS, Chalmers J, van der Kooi-Pol MM, van Dijl JM, Ryan RP, Hunter WN, Palmer T. Heterogeneity in ess transcriptional organization and variable contribution of the Ess/Type VII protein secretion system to virulence across closely related Staphylocccus aureus strains. Molecular Microbiology 2014, 93(5), 928-943.
  • Dow JM, Grahl S, Ward R, Evans R, Byron O, Norman DG, Palmer T, Sargent F. Characterization of a periplasmic nitrate reductase in complex with its biosynthetic chaperone. FEBS Journal 2014, 281(1), 246-260.
  • McDowall JS, Murphy BJ, Haumann M, Palmer T, Armstrong FA, Sargent F. Bacterial formate hydrogenlyase complex. Proceedings of the National Academy of Sciences of the United States of America 2014, 111, e3948-e3956.
  • Hamilton JJ, Marlow VL, Buchanan G, Guo M, Owen R, de Assis Alcoforado Costa M, Trost M, Coulthurst SJ, Palmer T, Stanley-Wall NR, Sargent F. A holin and an endopeptidase are essential for chitinolytic protein secretion in Serratia marcescens. Journal of Cell Biology 2014, 207(5), 615-626.

• Conference Proceedings (inc. Abstract)

  • Goh BHT, Conneely M, Kneuper H, Palmer T, Klaseboer E, Khoo BC, Campbell P. High-speed imaging of ultrasound-mediated bacterial Biofilm Disruption. In: 6th European Conference of the International Federation for Medical and Biological Engineering. 2014, Dubrovnik, Croatia: Springer Verlag.

• Reviews

  • Palmer T, Finney A, Saha CK, Atkinson GC, Sargent F. A holin/peptidoglycan hydrolase-dependent protein secretion system. Molecular Microbiology 2021, 115(3), 345-355.
  • Palmer T, Stansfeld PJ. Targeting of proteins to the twin-arginine translocation pathway. Molecular Microbiology 2020, 113(5), 861-871.
  • Unnikrishnan M, Constantinidou C, Palmer T, Pallen MJ. The Enigmatic Esx Proteins: Looking Beyond Mycobacteria. Trends in Microbiology 2017, 25(3), 192-204.