Dr Michael Gotsbacher

PhD
Postdoctoral Research Associate
School of Medical Sciences (Pharmacology)

Telephone 02-935-16727
Fax 02-935-14717

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Biographical details

Postdoctoral Research Associate at University of Sydney (2014-)

Project Chemist, Agrifor Scientific (2013-2014)

PhD in Chemical Biology at Macquarie University, Sydney (2007-2012)

MSc in Pharmacy at University of Vienna (2006)

Research interests

My research revolves around natural products, their chemical diversity, structural analysis, and potential therapeutic value. Currently, my focus lies on small molecular weight, hydroxamic acid based Fe(III)-chelating compounds, known as siderophores, and their application in diseases with Fe dyshomeostasis. In our lab, we are investigating the many faces of one such chelator, the clinically used desferrioxamine B (DFOB) and I’m interested in its application in Parkinson’s disease (PD). PD is characterised by the loss of dopaminergic neurons in the substantia nigra region of the brain. This neuronal loss is partially attributed to oxidative stress, which is exacerbated by the pathological presence of excess iron in the substantia nigra. Through semi-synthetically creating lipophilic DFOB variants, we aim to sequester excess iron and minimise its redox potential, which is considered of therapeutic value. Our collaborators at the Florey Institute in Melbourne have and are testing our compounds in a PD mouse model.
Besides my work on PD relevant DFOB analogues, there are several smaller projects I’m interested adn involved in. In one recent paper in ACS Chemical Biology, we aimed to delineate the endogenous enzymatic cascade resulting in DFOB, through precursor directed biosynthesis, LCMS analysis and isolation of metabolites. We showed the order in which the heterotrimer DFOB is assembled during the final step of its biosynthesis. I co-supervised an Honours’ project that aimed to synthesise isoform-selective histone deacetylase (HDAC) inhibitors. The student synthesised, characterised and tested a library of hydroxamic acid-based analogues with varying structural motifs that allow to probe for isoform selectivity.

Current projects

  • Desferrioxamine B (DFOB) and lipophilic analogues in the treatment of Parkinson's Disease and other conditions implicating iron dyshomeostasis
  • Synthesis and in vitro testing of isoform-selective histone deacetylase (HDAC) inhibitors
  • Precursor directed biosynthesis of DFOB variants
  • Chemical biology of other siderophores, such as ornibactin from Burkholderia vietnamensis

Associations

Royal Australian Chemical Institute, International Biometals Society, Austrian Pharmaceutical Society

Selected publications

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Journals

  • Gotsbacher, M., Telfer, T., Witting, P., Double, K., Finkelstein, D., Codd, R. (2017). Analogues of desferrioxamine B designed to attenuate iron-mediated neurodegeneration: synthesis, characterisation and activity in the MPTP-mouse model of Parkinson's disease. Metallomics, 9(7), 852-864. [More Information]
  • Gotsbacher, M., Cho, S., Kwon, H., Karuso, P. (2017). Daptomycin, a last-resort antibiotic, binds ribosomal protein S19 in humans. Proteome Science, 15(1), 1-15. [More Information]
  • Richardson-Sanchez, T., Tieu, W., Gotsbacher, M., Telfer, T., Codd, R. (2017). Exploiting the biosynthetic machinery of Streptomyces pilosus to engineer a water-soluble zirconium(iv) chelator. Organic and Biomolecular Chemistry, 15(27), 5719-5730. [More Information]
  • Telfer, T., Gotsbacher, M., Soe, C., Codd, R. (2016). Mixing Up the Pieces of the Desferrioxamine B Jigsaw Defines the Biosynthetic Sequence Catalyzed by DesD. ACS Chemical Biology, 11(5), 1452-1462. [More Information]
  • Gotsbacher, M., Karuso, P. (2015). New antimicrobial bromotyrosine analogues from the sponge Pseudoceratina purpurea and its predator Tylodina corticalis. Marine Drugs, 13(3), 1389-1409. [More Information]

2017

  • Gotsbacher, M., Telfer, T., Witting, P., Double, K., Finkelstein, D., Codd, R. (2017). Analogues of desferrioxamine B designed to attenuate iron-mediated neurodegeneration: synthesis, characterisation and activity in the MPTP-mouse model of Parkinson's disease. Metallomics, 9(7), 852-864. [More Information]
  • Gotsbacher, M., Cho, S., Kwon, H., Karuso, P. (2017). Daptomycin, a last-resort antibiotic, binds ribosomal protein S19 in humans. Proteome Science, 15(1), 1-15. [More Information]
  • Richardson-Sanchez, T., Tieu, W., Gotsbacher, M., Telfer, T., Codd, R. (2017). Exploiting the biosynthetic machinery of Streptomyces pilosus to engineer a water-soluble zirconium(iv) chelator. Organic and Biomolecular Chemistry, 15(27), 5719-5730. [More Information]

2016

  • Telfer, T., Gotsbacher, M., Soe, C., Codd, R. (2016). Mixing Up the Pieces of the Desferrioxamine B Jigsaw Defines the Biosynthetic Sequence Catalyzed by DesD. ACS Chemical Biology, 11(5), 1452-1462. [More Information]

2015

  • Gotsbacher, M., Karuso, P. (2015). New antimicrobial bromotyrosine analogues from the sponge Pseudoceratina purpurea and its predator Tylodina corticalis. Marine Drugs, 13(3), 1389-1409. [More Information]

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