Graham H. Coombs

ORCID: 0000-0002-9870-2005
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About
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Research Areas
  • Research on Leishmaniasis Studies
  • Trypanosoma species research and implications
  • Parasitic Infections and Diagnostics
  • Peptidase Inhibition and Analysis
  • Reproductive tract infections research
  • Enzyme Production and Characterization
  • Blood Coagulation and Thrombosis Mechanisms
  • Biochemical and Molecular Research
  • Parasites and Host Interactions
  • Toxoplasma gondii Research Studies
  • Coccidia and coccidiosis research
  • Autophagy in Disease and Therapy
  • Polyamine Metabolism and Applications
  • Enzyme function and inhibition
  • Insect and Pesticide Research
  • Insect symbiosis and bacterial influences
  • Amoebic Infections and Treatments
  • HIV/AIDS drug development and treatment
  • Protist diversity and phylogeny
  • Synthesis and Biological Evaluation
  • Malaria Research and Control
  • Insect Resistance and Genetics
  • Insect Pest Control Strategies
  • Signaling Pathways in Disease
  • Parasite Biology and Host Interactions

Monash University
2024

University of South Australia
2024

University of Strathclyde
2011-2021

Glasgow Life
2011-2014

University of Glasgow
2002-2012

Wellcome Centre for Molecular Parasitology
1996-2012

Wellcome Trust
2011-2012

Xiaomi (China)
2011

Weatherford College
2006-2009

Newcastle University
2007

We describe the genome sequence of protist Trichomonas vaginalis , a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds ∼160-megabase genome, reflecting recent massive expansion genetic material. This expansion, in conjunction with shaping metabolic pathways that likely transpired through lateral gene transfer from bacteria, amplification specific families implicated pathogenesis phagocytosis host proteins may exemplify adaptations parasite...

10.1126/science.1132894 article EN Science 2007-01-12

Visceral leishmaniasis is a potentially fatal disease endemic to large parts of Asia and Africa, primarily caused by the protozoan parasite Leishmania donovani . Here, we report high-quality reference genome sequence for strain L. from Nepal, use this study variation in set 16 related clinical lines, isolated visceral patients same region, which also differ their response vitro drug susceptibility. We show that whole-genome data reveals genetic structure within these lines not shown...

10.1101/gr.123430.111 article EN Genome Research 2011-10-28

Leishmania mexicana mutants lacking cysteine proteinase genes cpa (delta cpa), cpb cpb), or both and cpa/cpb) have been generated by targeted gene disruption. Delta produce a disease phenotype in BALB/c mice close to that of wild-type L. mexicana, but delta are much less infective, producing very slowly growing small lesions, cpa/cpb double do not induce lesion growth. Immunologic analysis Ab isotype during infection splenocyte IFN-gamma, IL-2, IL-4 production following stimulation with Ag...

10.4049/jimmunol.161.12.6794 article EN The Journal of Immunology 1998-12-15

Proline metabolism has been studied in procyclic form Trypanosoma brucei. These parasites consume six times more proline from the medium when glucose is limiting supply than this carbohydrate present as an abundant energy source. The sensitivity of T. brucei to oligomycin increases by three orders magnitude are obliged catabolize depleted glucose. This indicates that oxidative phosphorylation far important latter case available and needs parasite can be fulfilled substrate level alone. A...

10.1074/jbc.m414274200 article EN cc-by Journal of Biological Chemistry 2005-01-23

The mammalian form of the protozoan parasite Leishmania mexicana contains high activity a cysteine proteinase (LmCPb) encoded on tandem array 19 genes (lmcpb). Homozygous null mutants for lmcpb have been produced by targeted gene disruption. All life-cycle stages mutant can be cultured in vitro, demonstrating that is not essential growth or differentiation parasite. However, exhibits marked phenotype affecting virulence-- its infectivity to macrophages reduced 80%. are as efficient wild-type...

10.1073/pnas.93.12.6008 article EN Proceedings of the National Academy of Sciences 1996-06-11

Cellular remodeling during differentiation is essential for life-cycle progression of many unicellular eukaryotic pathogens such as Leishmania, but the mechanisms involved are largely uncharacterized. The role endosomal sorting in was analyzed Leishmania major by overexpression a dominant-negative ATPase, VPS4. VPS4(E235Q) accumulated vesicles from endocytic pathway, and mutant L. deficient endosome sorting. Mutant parasites failed to differentiate obligate infective metacyclic promastigote...

10.1074/jbc.m512307200 article EN cc-by Journal of Biological Chemistry 2006-02-24

Liver and serum concentrations of antimony in the mouse have been determined after administration sodium stibogluconate free, liposomal niosomal form. High liver low values were attained by use both vesicular formulations. Niosomal was shown to be more active than free drug against experimental murine visceral leishmaniasis, an effect apparently dependent on maintaining high levels infected reticuloendothelial system.

10.1111/j.2042-7158.1986.tb04623.x article EN Journal of Pharmacy and Pharmacology 1986-07-01

SUMMARY A new method is described which has made possible the long-term axenic cultivation of Leishmania mexicana amastigotelike forms in Schneider's Drosophila medium supplemented with 2% (v/v) foetal calf serum. Unlike previous methods, it utilizes direct culture parasites obtained from lesions infected animals rather than adaptation promastigotes vitro . Ultrastructural (possession megasomes), biochemical (cysteine proteinase activity and gelatin SDS-PAGE banding pattern) infectivity (...

10.1017/s0031182000074102 article EN Parasitology 1992-10-01

Abstract Suppression of Leishmania donovani liver amastigotes by sodium stibogluconate has been determined in a murine model experimental visceral leishmaniasis. Niosomal and liposomal drug formulations were equiactive both increased efficacy an order magnitude compared with that free drug. Niosomes containing 30 mol % cholesterol prepared from three different non-ionic surfactants no significant difference activity was detected among the drug-loaded niosomes. Both negatively charged neutral...

10.1111/j.2042-7158.1988.tb05210.x article EN Journal of Pharmacy and Pharmacology 1988-03-01

SUMMARY A rapid method for the bulk isolation of purified Leishmania mexicana amastigotes from parasite-induced lesions in experimentally infected mice is described. The procedure includes purification steps based on differences net cell charge, lysis susceptibility and buoyant density between parasite host cells. Yields up to 2 × 10 untransformed with minimal contamination cells debris can be obtained. At least 90 % are viable as judged by light electron microscopy, staining their lysosomes...

10.1017/s0031182000066889 article EN Parasitology 1981-06-01

Abstract Infection with lesion-derived Leishmania mexicana amastigotes inhibited LPS-induced IL-12 production by mouse bone marrow-derived macrophages. This effect was associated expression of cysteine peptidase B (CPB) because CPB deletion mutants had limited ability to inhibit production, whereas preincubation cells a inhibitor, cathepsin inhibitor IV, able suppress the wild-type amastigotes. resulted in time-dependent proteolytic degradation IκBα and IκBβ related protein NF-κB. did not...

10.4049/jimmunol.173.5.3297 article EN The Journal of Immunology 2004-09-01

A library consisting of about half 800 000 possible peptidotriazoles on 450 beads was prepared by solid-phase peptide synthesis combined with a regiospecific copper(I)-catalyzed 1,3-dipolar cycloaddition between resin-bound alkyne and protected amino azide. The central [1,2,3]-triazole flanked each side two randomized acids introduced in combinatorial approach. Importantly, the formation triazole could be performed quantitatively fashion. screened solid phase for inhibitory effect against...

10.1021/cc020085v article EN Journal of Combinatorial Chemistry 2004-04-02
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