Stubbs, Keith - University of Western Australia - School of Chemistry and Biochemistry

研究领域

Carbohydrates are present in every living system from prokaryotes to eukaryotes and traditionally, have been known for their role in the structural integrity of plants and as energy sources. Recently, however, carbohydrates have been shown to be involved in a variety of fundamental biological processes such as protein folding and trafficking, as well as cellular signaling and recognition. As we gain greater understanding into the roles that carbohydrates play at the cellular level, scientists are faced with new challenges. On the chemistry side, unique carbohydrate-based tools need to be developed and in turn used to investigate the specific roles that a single mono- or polysaccharide plays in the dynamics of the cell in order to keep up with the biochemical discovery of new glycan structures and the enzymes that regulate them. My research aims are to address the development of such tools which involves synthetic, medicinal and biochemical approaches. Very brief overviews of current research areas are outlined below. Developing tools to study carbohydrate-processing enzymes in human health and disease: Various human diseases are caused by improper function of a specific carbohydrate-processing enzyme. We aim to develop tools to study these enzymes and then use the information gathered to produce therapeutics. This is done through the use of synthetic and medicinal chemistry approaches. We have numerous collaborators in Canada and the UK working with us on these projects. Investigations into human milk oligosaccharides: One class of carbohydrates is those found in human breast milk and are termed human milk oligosaccharides (HMOs). These compounds are critical for infant health as they provide nutrition for bifidobacteria (found in the human intestinal tract) which provide great benefits to infants such as nutrients, prevention of pathogenic bacterial growth and suppression of inflammatory and allergic responses. To date though, limited chemical tools have been generated to study these fundamentally important molecules. We have several collaborators in Japan working with us on this project. Antimicrobial resistance: As the threat of antibiotic resistance grows with each passing year new therapeutic targets are required. We have numerous targets and approaches to developing new therapeutics. This is done through the use of synthetic and medicinal chemistry approaches. We have numerous collaborators in Australia and Canada working with us on these projects. Investigations into the mechanism and biochemistry of carbohydrate-processing enzymes involved in plant cell wall degradation: Of increasing interest is how bacteria utilise plant-based materials and their direct importance to humans, as we are only able to utilise these carbohydrates for metabolism due to the action of unique enzymes produced by the bacteria living in our gastrointestinal tract. We have numerous collaborators in Canada and the UK working with us on these projects. Herbicide resistance: The development and use of herbicides in agriculture has improved crop yields worldwide, but like antimicrobial resistance, herbicide resistance is also highly prevalent and is threatening food production. In collaboration with Professor Joshua Mylne (UWA) we have discovered new compounds with herbicidal potency and methods to assess the ability of these compounds to act as herbicides in the field. This project offers exciting opportunities in synthetic organic and medicinal chemistry. Microfluidics: The development of new methodology in organic chemistry is always required to improve reaction yields and discover new reactions. In collaboration with Professor Colin Raston we have a microfluidic platform that can be utilized to explore new chemical reactions and also develop methodology to improve on existing methodologies. This project offers exciting opportunities in general synthetic organic chemistry. The laboratory is always very welcoming for people interested in chemistry and/or biochemistry. If you have any interests in these areas please feel free to contact me by email and I am happy to discuss the exciting opportunities available.

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Hattie, M., Cekic, N., Debowski, A.W., Vocadlo, D.J., Stubbs, K.A. 2016, 'Modifying the phenyl group of PUGNAc: Reactivity tuning to deliver selective inhibitors for N-acetyl-d-glucosaminidases', ORGANIC & BIOMOLECULAR CHEMISTRY, 14, 12, pp. 3193-3197. Detail Cekic, N., Heinonen, J.E., Stubbs, K.A., Roth, C., He, Y., Bennet, A.J., McEachern, E.J., Davies, G.J., Vocadlo, D.J. 2016, 'Analysis of transition state mimicry by tight binding aminothiazoline inhibitors provides insight into catalysis by human: O-GlcNAcase', Chemical Science, 7, 6, pp. 3742-3750. Detail Perley-Robertson, G.E., Yadav, A.K., Winogrodzki, J.L., Stubbs, K.A., Mark, B.L., Vocadlo, D.J. 2016, 'A Fluorescent Transport Assay Enables Studying AmpG Permeases Involved in Peptidoglycan Recycling and Antibiotic Resistance', ACS Chemical Biology, 11, 9, pp. 2626-2635. Detail Gandy, M.N., Byrne, L.T., Stubbs, K.A. 2015, 'A simple and robust preparation of N-acetylindoxyls: Precursors for indigogenic substrates', ORGANIC & BIOMOLECULAR CHEMISTRY, 13, 3, pp. 905-908. Detail Gandy, M.N., Corral, M.G., Mylne, J.S., Stubbs, K.A. 2015, 'An interactive database to explore herbicide physicochemical properties', ORGANIC & BIOMOLECULAR CHEMISTRY, 13, 20, pp. 5586-5590. Detail Gandy, M.N., Raston, C.L., Stubbs, K.A. 2015, 'Photoredox catalysis under shear using thin film vortex microfluidics', Chemical Communications, 51, 55, pp. 11041-11044. Detail Watson, M.E., Diepeveen, L.A., Stubbs, K.A., Yeoh, G.C. 2015, 'Glycosylation-related diagnostic and therapeutic drug target markers in hepatocellular carcinoma', Journal of Gastrointestinal and Liver Diseases, 24, 3, pp. 349-357. Detail Coyle, T., Brumer, H., Stubbs, K.A. 2015, 'An improved preparation of some aryl a- L -arabinofuranosides for use as chromogenic substrates for a- L -arabinofuranosidases', Canadian Journal of Chemistry, 93, 11, pp. 1176-1180. Detail Debowski, A.W., Sehnal, M., Liao, T., Stubbs, K.A., Marshall, B.J., Benghezal, M. 2015, 'Expansion of the tetracycline-dependent regulation toolbox for Helicobacter pylori', Applied and Environmental Microbiology, 81, 23, pp. 7969-7980. Detail Kampmann, S.S., Skelton, B.W., Yeoh, G.C., Abraham, L.J., Lengkeek, N.A., Stubbs, K.A., Heath, C.H., Stewart, S.G. 2015, 'The synthesis and fluorescence profile of novel thalidomide analogues', Tetrahedron, 71, 42, pp. 8140-8149. Detail Hattie, M., Ito, T., Debowski, A.W., Arakawa, T., Katayama, T., Yamamoto, K., Fushinobu, S., Stubbs, K.A. 2015, 'Gaining insight into the catalysis by GH20 lacto-N-biosidase using small molecule inhibitors and structural analysis', CHEMICAL COMMUNICATIONS, 51, 81, pp. 15008-15011. Detail Piek, S.H., Wang, Z., Ganguly, J., Lakey, A.M., Bartley, S.N., Mowlaboccus, S., Anandan, A., Stubbs, K.A., Scanlon, M.J., Vrielink, A., Azadi, P., Carlson, R.W., Kahler, C. 2014, 'The Role of Oxidoreductases in Determining the Function of the Neisserial Lipid A Phosphoethanolamine Transferase Required for Resistance to Polymyxin', PLoS ONE, 9, 9, pp. e106513. Detail Singh, A.K., Pluvinage, B., Higgins, M.A., Dalia, A.B., Woodiga, S.A., Flynn, M., Lloyd, A.R., Weiser, J.N., Stubbs, K.A., Boraston, A.B., King, S.J. 2014, 'Unravelling the Multiple Functions of the Architecturally Intricate Streptococcus pneumoniae β-galactosidase, BgaA', PLoS Pathogens, 10, 9, pp. e1004364. Detail Clayton, E.K., Hattie, M., Debowski, A.W., Stubbs, K.A. 2014, 'Synthesis of Carbohydrate-based Natural Products from Leonurus japonicus and their Biological evaluation as Anti-oxidants', Australian Journal of Chemistry, 67, 10, pp. 1461-1470. Detail Eggers, P.K., Eroglu, E., Becker, T.L., Chen, X., Vimalanathan, K., Stubbs, K.A., Smith, S.M., Raston, C.L. 2014, 'Nitrate uptake by p-phosphonic acid or p-(trimethylammonium)methyl calix[8]arene stablized laminar materials', RSC Advances, 4, 89, pp. 48348-48352. Detail Gandy, M.N., Raston, C.L., Stubbs, K.A. 2014, 'Towards aryl C-N bond formation in dynamic thin films', ORGANIC & BIOMOLECULAR CHEMISTRY, 12, 26, pp. 4594-4597. Detail Stubbs, K.A. 2014, 'Activity-based proteomics probes for carbohydrate-processing enzymes: Current trends and future outlook', Carbohydrate Research, 390, 1, pp. 9-19. Detail Yasmin, L., Stubbs, K.A., Raston, C.L. 2014, 'Vortex fluidic promoted Diels-Alder reactions in an aqueous medium', Tetrahedron Letters, 55, 14, pp. 2246-2248. Detail Yasmin, L., Eggers, P.K., Skelton, B.W., Stubbs, K.A., Raston, C.L. 2014, 'Thin film microfluidic synthesis of fluorescent highly substituted pyridines', Green Chemistry, 16, 7, pp. 3450-3453. Detail Kim, R.Q., Offen, W.A., Davies, G.J., Stubbs, K.A. 2014, 'Structural enzymology of Helicobacter pylori methylthioadenosine nucleosidase in the futalosine pathway', ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 70, 1, pp. 177-185. Detail