Profile

Career

2010 -	Senior Lecturer	Department of Biology, University of York
2002 - 2010	Lecturer	Department of Biology, University of York
2000 - 2002	Postdoctoral Research Fellow	Department of Molecular Biology and Biotechnology, University of Sheffield
1998 - 2000	Postdoctoral Research Fellow	Molecular Microbiology department at the John Innes Centre, Norwich
1995 - 1998	PhD in Biochemistry	Birmingham University
1992 - 1995	BSc (Hons)	Bristol University

Research

Overview

The Thomas group has two main interests that are linked by the bacterium Escherichia coli. We are interested in the mechanisms used by different bacteria, mainly human pathogens, to utilise the important host-derived molecule sialic acid. This includes how this sugar acid is transported across the inner membrane of bacteria and here we study the sialic acid-specific tripartite ATP-independent periplasmic (TRAP) transporter from Haemophilus influenzae as our main system. We also used constraint-based modelling to understand the obligate symbiosis between a number of bacteria and their insect hosts, focussing mainly on the interaction between the E. coli relative Buchnera aphidicola and its aphid host.

Discoveries

We have recently provided the first mechanistic detail on the function of a TRAP transporter, using the SiaPQM sialic acid transporter from H. influenzae and have discovered a sialic acid mutarotase that is encoded by some bacterial pathogens to help that acquire sialic acid effectively from their host. Also, we have helped in the annotation and interpretation of the aphid genome sequence in relation to its symbiotic interaction with Buchnera. sp.

Current projects

• Systems level analysis of animal metabolism by multicompartmental graph- and constraints-based modelling (Funding body: BBSRC/ANR Systems Biology)
• Characterisation of the function and mechanism of a binding- protein dependent secondary transporter (Funding body: BBSRC)

Research group(s)

Status	Name	Project
Post doc	Dr Sandy Macdonald	Systems level analysis of animal metabolism by multicompartmental graph- and constraints-based modelling
Student	Abbas Maqbool	Development of peptide specific ESRs as diagnostic tools
Student	Daniel Bawdon	Identification of bacterial transporters for hydroxyalkylcysteines: a novel target for reducing axillary malodour (BBSRC Industrial CASE with Unilever)

Available PhD research projects

Molecular dissection of sialic acid transporters involved in bacterial virulence (for 2012 - 13)

recruited as a surface molecule by some human pathogenic bacteria enabling them to effectively ‘hide’ from the innate immune response. We have discovered multiple routes by which bacteria take up sialic acid, which is essential for this immune evasion process, and in this project the student will continue work on the SiaPQM sialic acid transporter from Heamophilus influenzae. This transporter is also a model for the tripartite ATP-independent periplasmic (TRAP) transporter family and in this project the student will investigate the function and mechanism of this transporter using molecular and biochemical methods. The TRAP transporters contain a soluble substrate binding protein component, but yet are secondary transporters, and the project will build on exciting data we have suggesting how the binding protein docks with the membrane domains of the transporter during the transport cycle, an essential step in the process which is not understood for any TRAP transporter.

References

Fischer, M., Zhang, Q.Y., Hubbard, R.E. and Thomas G.H. (2010) Caught in a TRAP: substrate binding proteins in secondary transport. Trends in Microbiology. 35(1):68-86.

Mulligan C, Geertsma ER, Severi E, Kelly DJ, Poolman B, Thomas GH (2009) The substrate-binding protein imposes directionality on an electrochemical sodium gradient-driven TRAP transporter. Proc Natl Acad Sci U S A. 106(6):1778-83.

Severi, E, Hood, DW and Thomas GH. (2007) Sialic acid utilization by bacterial pathogens. Microbiology 153:2817-22.

Publications

Selected publications

MacDonald SJ, Thomas GH, Douglas AE (2011) Genetic and metabolic determinants of nutritional phenotype in an insect-bacterial symbiosis. Mol Ecol. 2011 20(10):2073-84.

Severi E, Müller A, Potts JR, Leech A, Williamson D, Wilson KS and Thomas GH (2008) Sialic acid mutarotation is catalyzed by the Escherichia coli beta-propeller protein YjhT J Biol Chem 283: 4841-9

Thomas GH, Zucker J, Macdonald SJ, Sorokin A, Goryanin I, Douglas AE (2009) A fragile metabolic network adapted for cooperation in the symbiotic bacterium Buchnera aphidicola. BMC Syst Biol 3: 24

Mulligan C, Geertsma ER, Severi E, Kelly DJ, Poolman B, Thomas GH (2009) The substrate-binding protein imposes directionality on an electrochemical sodium gradient-driven TRAP transporter. Proc Natl Acad Sci U S A. 106(6): 1778-83.

Full publications list

2011

MacDonald SJ, Thomas GH, Douglas AE (2011) Genetic and metabolic determinants of nutritional phenotype in an insect-bacterial symbiosis. Mol Ecol. 2011 20(10):2073-84.

Maqbool, A., Levdikov, V.M., Blagova, E., Herve, M., Horler, R.S.P., Wilkinson, A.J. and Thomas, G.H. (2011) Compensating stereochemical changes allow murein tripeptide to be accommodated in a conventional peptide binding protein J. Biol. Chem. jbc.M111.267179. First Published on June 24, 2011, doi:10.1074/jbc.M111.267179.

2010

Fischer, M., Zhang, Q.Y., Hubbard, R.E. and Thomas G.H. (2010) Caught in a TRAP: substrate binding proteins in secondary transport. Trends in Microbiology. in press.

Mulligan, C., Fischer, M. and Thomas G.H. (2010) Tripartite ATP-independent periplasmic (TRAP) transporters in bacteria and archaea. FEMS Microbiology Reviews May 28. [Epub ahead of print].

The International Aphid Genomics Consortium (2010) Genome Sequence of the Pea Aphid Acyrthosiphon pisum. PLoS Biol 8(2):e1000313.

Wilson ACC, Ashton PD, Calevro F, Charles H, Colella S, Febvay G, Jander G, Kushlan P, Macdonald SA, Schwartz J, Thomas GH and Douglas AE (2010) Genomic insight into the amino acid relations of the pea aphid Acyrthosiphon pisum with its symbiotic bacterium Buchnera aphidicola. Insect Molecular Biology 19 (Suppl. 2), 249–258.

Ramsey JS, MacDonald SJ, Jander G, Nakabachi A, Thomas GH and Douglas AE (2010) Genomic evidence for complementary purine metabolism in the pea aphid Acyrthosiphon pisum and its symbiotic bacterium Buchnera aphidicola. Insect Molecular Biology 19 (Suppl. 2), 241–248.

Severi, E., Hosie, A.H.F., Hawkhead, J., and Thomas G.H. (2010) Characterisation of a novel sialic acid transporter of the sodium solute symporter (SSS) family and in vivo comparison with known bacterial sialic acid transporters. FEMS Microbiolgy Letters. 304:47-54.

2009

Jackson, A.P., Thomas, G.H., Parkhill, J. and Thomson, N.R. (2009) Evolutionary diversification of an ancient gene family (Rhs) through C-terminal displacement. BMC Genomics 10(1):584.

Thomas, G.H. (2009) Homes for the orphans: utilization of multiple substrate binding proteins by ABC transporters. Mol Microbiol.

Horler, R.S.P., Müller, A., Williamson, D.C., Potts, J.R., Wilson, K.S. and Thomas GH (2009) Furanose-specific sugar transport: characterisation of a bacterial galactofuranose binding protein. J. Biol. Chem. 284(45):31156-63.

Basavanna S, Khandavilli S, Yuste J, Cohen JM, Hosie AH, Webb AJ, Thomas GH, Brown JS (2009) Screening of Streptococcus pneumoniae ABC transporter mutants demonstrates that LivJHMGF, a branched-chain amino acid ABC transporter, is necessary for disease pathogenesis. Infect Immun. 77(8):3412-23.

Thomas GH, Zucker J, Macdonald SJ, Sorokin A, Goryanin I, Douglas AE (2009) A fragile metabolic network adapted for cooperation in the symbiotic bacterium Buchnera aphidicola. BMC Syst Biol. 3:24.

Mulligan C, Geertsma ER, Severi E, Kelly DJ, Poolman B, Thomas GH (2009) The substrate-binding protein imposes directionality on an electrochemical sodium gradient-driven TRAP transporter. Proc Natl Acad Sci U S A. 106(6):1778-83.

Md-Saleh SR, Chilvers EC, Kerr KG, Milner SJ, Snelling AM, Weber JP, Thomas GH, Duhme-Klair AK, Routledge A. (2009) Synthesis of citrate-ciprofloxacin conjugates. Bioorg Med Chem Lett. 19(5):1496-8.

Horler RS, Butcher A, Papangelopoulos N, Ashton PD, Thomas GH (2009) EchoLOCATION: an in silico analysis of the subcellular locations of Escherichia coli proteins and comparison with experimentally derived locations. Bioinformatics. 25(2):163-6.


2008

Severi, E., Müller, A., Potts, JR., Leech, A., Williamson, D., Wilson, KS and Thomas GH (2008) Sialic acid mutarotation is catalysed by the Escherichia coli beta-propeller protein YjhT. J. Biol. Chem. 283:4841-9.

2007

Severi, E, Hood, DW and Thomas GH. (2007) Sialic acid utilization by bacterial pathogens. Microbiology 153:2817-22.

Mulligan, C., Kelly, D.J. and Thomas, G.H. (2007) Tripartite ATP-Independent Periplasmic Transporters: Application of a Relational Database for Genome-Wide Analysis of Transporter Gene Frequency and Organization. J Mol Microbiol Biotechnol. 12:218-26.

Chaudhuri R.R. and Thomas G.H. (2007) Understanding the Model and the Menace: a Postgenomic View of Escherichia coli. In Bacterial Pathogenomics. Edited by Mark J. Pallen, M.J., Nelson, K.E. and Preston, G.M. ASM Press May 2007.

Thomas GH (2007) Napoleon and typhus: a tale of two generals. Microbiology Today Feb 2007.

2006

Muller, A., Severi, E., Mulligan, C., Watts, A.G., Kelly, D.J., Wilson, K.S., Wilkinson, A.J. and Thomas GH. (2006) Conservation of structure and mechanism in primary and secondary transporters exemplified by SiaP, a sialic acid binding virulence factor from Haemophilus influenzae. J Biol Chem. 281:22212-22.

Riley, M., Abe, T., Arnaud, M.B., Berlyn, M.K., Blattner, F.R., Chaudhuri, R.R., Glasner, J.D., Horiuchi, T., Keseler, I.M., Kosuge, T., Mori, H., Perna, N.T., Plunkett, G. 3rd, Rudd, K.E., Serres, M.H. and Thomas, G.H., Thomson, N.R., Wishart, D. and Wanner, B.L. (2006) Escherichia coli K-12: a cooperatively developed annotation snapshot--2005. Nucleic Acids Res. 34:1-9.

Prickett, M.D., Page, M., Douglas, A.E. and Thomas GH. (2006) BuchneraBASE: a post-genomic resource for Buchnera sp. APS. Bioinformatics. 22:641-2.

Thomas GH, Southworth T, Leon-Kempis MR, Leech A, Kelly DJ. (2006) Novel ligands for the extracellular solute receptors of two bacterial TRAP transporters. Microbiology. 152:187-98.

2005

Severi, E., Randle, G., Kivlin, P., Whitfield, K., Young, R., Moxon, R., Kelly, D., Hood, D. and Thomas, G.H. (2005) Sialic acid transport in Haemophilus influenzae is essential for lipopolysaccharide sialylation and serum resistance and is dependent on a novel tripartite ATP-independent periplasmic transporter. Mol Microbiol. 58:1173-85.

Muller, A., Thomas, G.H., Horler, R., Brannigan, J.A., Blagova, E., Levdikov, V.M., Fogg, M.J., Wilson, K.S. and Wilkinson, A.J. (2005) An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein. Mol Microbiol. 57:143-55.

Thomas, G.H. (2005) The nicer side of E. coli: Escherichia coli as a model organism. The Biochemist. Dec 2005.

Thomas, G.H. (2005) Microbes in the air: John Tyndall and the spontaneous generation debate. Microbiology Today. Nov 2005.

External activities

Memberships

• Member of the Society for General Microbiology (SGM)
• Associate member of eMEP
• Member of the xBASE steering committee

Editorial duties

• Associate editor of Microbiology