Professor Coombs joined the University of Strathclyde in October 2006 to become Head of the new Institute of Pharmacy and Biomedical Sciences and Head of the School of Pharmacy. He is also Professor of Biochemical Parasitology. His research focuses on two unicellular parasitic protozoa, Leishmania, the causative agent of leishmaniasis, and Trichomonas, a very common sexually transmitted pathogen. These diseases cause widespread suffering and current treatment is unsatisfactory. The long term aim of his work is to underpin the development of novel therapies, either drugs or vaccines, which exploit unique biochemical aspects of the parasites.
Professor Coombs was trained as a biochemist and carried out postgraduate and postdoctoral research on the mode of action of antiparasite drugs before moving to Glasgow in 1974 to establish his own research group specialising in biochemical parasitology. Since then he has been active in elucidating biochemical adaptations of a range of parasitic protoza, including pioneering studies on Leishmania amastigotes and peptidases of trypanosomatids. His research output is reflected in the publication of more than 200 original papers, five books, several patents, the award of the Seymour H. Hunter prize by the Society of Protozoologists in 1986, and election as a Fellow of the Royal Society of Edinburgh in 1993. His group has extensive experience in a range of biochemical and parasitological methods and a keen interest in identification and characterisation of the biological function of parasite-specific proteins and exploiting these proteins as vaccines, drug targets and diagnostics.
"Characterisation of natural drug resistant L donovani isolates to guide epidemiological strategies" Institute of Tropical Medicine (ITM)
"Establishment of a biophotonic imaging system for in vivo biology " Wellcome Trust
"KALADRUG-R New tools for monitoring drug resistance and treatment response in visceral leishmaniasis in the Indian subcontinent (FP7 Health)" EU
"Analysing the roles of peptidases in Leishmania infectivity and pathogeni" MRC
Publications
Downing, T., Imamura, H., Decuypere, S., Clark, T. G., Coombs, G. H., Cotton, J. A., Hilley, J. D., de Doncker, S., Maes, I., Mottram, J. C., Quail, M. A., Rijal, S., Sanders, M., Schonian, G., Stark, O., Sundar, S., Vanaerschot, M., Hertz-Fowler, C., Duj (2011) Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. GENOME RESEARCH21, 2143-2156 [DOI: 10.1101/gr.123430.111 ]
Eschenlauer, S.C., Faria, M.S., Morrison, L.S., Bland, N., Ribeiro-Gomes, F.L., DosReis, G.A., Coombs, G.H., Lima, A.P., Mottram, J.C. (2009) Influence of parasite encoded inhibitors of serine peptidases in early infection of macrophages with Leishmania major. Cellular Microbiology11, 106-120 [DOI: 10.1111/j.1462-5822.2008.01243.x]
Proto, W.R, Castanys-Munoz, E., Black, A., Tetley, L., Moss, C.M., Juliano, L., Coombs, G.H., and Mottram, J.C. (2011) Trypanosoma brucei metacaspase 4 is a pseudopeptidase and a virulence factor. Journal of Biological Chemistry286, 39914-39925 [DOI: 10.1074/jbc.M111.292334 ]
Westrop, G.D., Georg, I., Coombs, G.H. (2009) The mercaptopyruvate sulfurtransferase of Trichomonas vaginalis links cysteine catabolism to the production of thioredoxin persulfide. Journal of Biological Chemistry284, 33485-33494
Duszenko, M., Ginger, M.L., Brennand, A., Gualdrón-López, M., Colombo, M., Coombs, G.H., Coppens, I., Jayabalasingham, B., Langsley, G., Lisboa de Castro, S., Menna-Barreto, R., Mottram, J.C., Navarro, M., Rigden, D.J., Romana, P.S., Stoka, V., Turk. B., (2011) Autophagy in Protists. Autophagy7, 127-158
Williams, R.A., Woods, K.L., Juliano, L., Mottram, J.C., and Coombs, G.H (2009) Characterization of unusual families of ATG8-like proteins and ATG12 in the protozoan parasite Leishmania major. Autophagy5, 1-14
Downing, T., Imamura, H., Decuypere, S., Clark, T. G., Coombs, G. H., Cotton, J. A., Hilley, J. D., de Doncker, S., Maes, I., Mottram, J. C., Quail, M. A., Rijal, S., Sanders, M., Schonian, G., Stark, O., Sundar, S., Vanaerschot, M., Hertz-Fowler, C., Duj (2011) Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. GENOME RESEARCH21, 2143-2156 [DOI: 10.1101/gr.123430.111 ]
Eschenlauer, S.C., Faria, M.S., Morrison, L.S., Bland, N., Ribeiro-Gomes, F.L., DosReis, G.A., Coombs, G.H., Lima, A.P., Mottram, J.C. (2009) Influence of parasite encoded inhibitors of serine peptidases in early infection of macrophages with Leishmania major. Cellular Microbiology11, 106-120 [DOI: 10.1111/j.1462-5822.2008.01243.x]
Proto, W.R, Castanys-Munoz, E., Black, A., Tetley, L., Moss, C.M., Juliano, L., Coombs, G.H., and Mottram, J.C. (2011) Trypanosoma brucei metacaspase 4 is a pseudopeptidase and a virulence factor. Journal of Biological Chemistry286, 39914-39925 [DOI: 10.1074/jbc.M111.292334 ]
Westrop, G.D., Georg, I., Coombs, G.H. (2009) The mercaptopyruvate sulfurtransferase of Trichomonas vaginalis links cysteine catabolism to the production of thioredoxin persulfide. Journal of Biological Chemistry284, 33485-33494
Duszenko, M., Ginger, M.L., Brennand, A., Gualdrón-López, M., Colombo, M., Coombs, G.H., Coppens, I., Jayabalasingham, B., Langsley, G., Lisboa de Castro, S., Menna-Barreto, R., Mottram, J.C., Navarro, M., Rigden, D.J., Romana, P.S., Stoka, V., Turk. B., (2011) Autophagy in Protists. Autophagy7, 127-158
Williams, R.A., Woods, K.L., Juliano, L., Mottram, J.C., and Coombs, G.H (2009) Characterization of unusual families of ATG8-like proteins and ATG12 in the protozoan parasite Leishmania major. Autophagy5, 1-14
Schaeffer, M., Schroeder, J., Heckeroth, A.R., Noack, S., Gassel, M., Mottram, J.C., Selzer, P.M., and Coombs, G.H. (2011) Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella. Antimicrobial Agents and Chemotherapy , [DOI: 10.1128/AAC.05528-11] Published (Epub)
Moya, I.A., Westrop, G.D., Coombs, G.H. and Honek, J.F. (2011) Mechanistic studies on the enzymatic processing of fluorinated methionine analogs by Trichomonas vaginalis methionine γ-lyase. Biochemical Journal438, 513-521 [DOI: 10.1042/BJ20101986.]
Williams, R.A., Westrop, G.D., and Coombs, G.H (2009) Two pathways for cysteine biosynthesis in Leishmania major. Biochemical Journal420, 451-462 [DOI: 10.1042/BJ20082441]
Decuypere, S., Vanaerschot, M., Brunker, K., Imamura, H., Müller, S., Rijal, S., Dujardin, J.C., and Coombs, G.H. (2011) Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background. PLOS Neglected Tropical Diseases , In Press
Silva, A.M., Cordeiro-da-Silva, A. and Coombs, G.H. (2011) Metabolic variation during development in culture of Leishmania donovani promastigotes. PLOS Neglected Tropical Diseases5, e1451 [DOI: 10.1371/journal.pntd.0001451]
t’Kindt, R., Scheltema, R.A., Jankevics, A., Brunker, K., Rijal, S., Dujardin, J.C., Breitling, R., Watson, D.G., Coombs, G.H., and Decuypere, S. (2010) Metabolomics to unveil and understand phenotypic diversity between pathogen populations. PLOS Neglected Tropical Diseases4, e904
Bryson K, Besteiro S, McGachy HA, Coombs GH, Mottram JC, Alexander J. (2009) Overexpression of the natural inhibitor of cysteine peptidases in Leishmania mexicana leads to reduced virulence and a Th1 response. Infection and Immunity77, 2971-2978 [DOI: 10.1128/IAI.00558-08]
Ambit, A., Woods, K.L., Cull, B., Coombs, G.H., and Mottram, J.C. (2011) Morphological events during the cell cycle of Leishmania major. EUKARYOTIC CELL10, 1429-1438 [DOI: 10.1128/EC.05118-11 ]
t'Kindt, R., Jankevics, A., Scheltema, R.A., Zheng, L., Watson, D.G., Dujardin, J.C., Breitling, R., Coombs, G.H., and Decuypere, S. (2010) Towards an unbiased metabolic profiling of protozoan parasites: optimisation of a Leishmania sampling protocol for HILIC-orbitrap analysis.. Analytical and Bioanalytical Chemistry398, 2059-2069
Steert, K., Berg, M., Mottram, J.C., Westrop, G.D., Coombs, G.H., Cos, P., Maes, L., Joossens, J., Van der Veken, P., Haemers, A., and Augustyns, K. (2010) α-ketoheterocycles as inhibitors of Leishmania mexicana cysteine protease CPB. ChemMedChem5, 1734-1748
Munday, J.C., McLuskey, K., Brown, E., Coombs, G.H., and Mottram, J.C. (2011) Oligopeptidase B deficient mutants of Leishmania major. Molecular and Biochemical Parasitology175, 49-57 [DOI: 10.1016/j.molbiopara.2010.09.003
]
Zheng, L., T'Kind, R., Decuypere, S., von Freyend, S.J., Coombs, G.H. and Watson, D.G. (2010) Profiling of lipids in Leishmania donovani using hydrophilic interaction chromatography in combination with Fourier transform mass spectrometry.. Rapid Communications in Mass Spectrometry24, 2074-2082
Richardson, J.M., Morrison, L.S., Bland, N.D., Bruce, S., Coombs, G.H., Mottram, J.C., and Walkinshaw, M.D (2009) Structures of Leishmania major orthologues of macrophage migration inhibitory factor. Biochemical and Biophysical Research Communications380, 422-448 [DOI: 10.1016/j.bbrc.2009.01.030]
Berg, M., Van der Veken, P., Joossens, J., Muthusamy, V., Breugelmans, M., Moss, C.X., Rudolf, J., Cos, P., Coombs, G.H., Maes, L., Haemers, A., Mottram J.C., and Augustyns, K. (2010) Design and evaluation of Trypanosoma brucei metacaspase inhibitors. Bioorganic & Medicinal Chemistry Letters20, 2001-2006
Coombs, G.H. (2010) Insights into the metabolomes of parasites.. Parasitology137, 1283
Scheltema, R.A., Decuypere, S., t’Kindt, R., Coombs, G.H. and Breitling, R. (2010) The potential of metabolomics for Leishmania research in the post-genomics era. Parasitology137, 1291-1302
McMillan, P.J., Patzewitz, E.M., Young, S.E., Westrop, G.D., Coombs, G.H., Engman, L., and Müller, S. (2009) Differential inhibition of high and low Mr thioredoxin reductases of parasites by organotelluriums supports the concept that low Mr thioredoxin reductases are good drug targets. Parasitology136, 27-33 [DOI: 10.1017/S0031182008005131]
Jecna, L., Svarovska, A., Besteiro, S., Mottram, J.C., Coombs, G.H., Volf, P (2009) Inhibitor of cysteine peptidase does not influence the development of Leishmania mexicana in Lutzomyia longipalpis. Journal of Medical Entomology46, 605-609 [DOI: 10.1603/033.046.0327]
Gornik, S.G., Westrop, G.D., Coombs, G.H., and Neil, D.M (2010) Molecular cloning and localization of a calpain-like protease from the abdominal muscle of Norway lobster Nephrops norvegicus. Molecular Biology Reports37, 2009-2019
Gornik, S.G., Albalat, A., Atkinson, R.J.A., Coombs, G.H. and Neil, D.M. (2010) The influence of defined ante-mortem stressors on the early post-mortem biochemical processes in the abdominal muscle of the Norway lobster, Nephrops norvegicus (Linnaeus, 1758).. Marine Biology Research6, 223-238
Albalat, A., Gornik, S.G., Atkinson, R.J.A., Coombs, G.H., and Neil, D.M. (2009) Effect of capture method on the physiology and nucleotide breakdown products in the Norway lobster (Nephrops norvegicus).. Marine Biology Research5, 441-450