Dr Michael Gotsbacher
- Senior Lecturer in Chemical Biology and Medicinal Chemistry (2023-)
- Lecturer in Chemical Biology and Medicinal Chemistry (2021-2022)
- Research Fellow at University of Sydney (2019-2021)
- Postdoctoral Research Associate at University of Sydney (2014-2018)
- Project Chemist, Agrifor Scientific (2013-2014)
- PhD in Chemical Biology at Macquarie University, Sydney (2007-2012)
- MSc in Pharmacy at University of Vienna (2006)
We are recruiting PhD students!
My lab has two research areas of interest. First, we are investigating if protein degradation is a viable approach to remove cytotoxic protein aggregates commonly found in neurodgenerative disorders. Our target protein of interest is TDP-43, which upon translocation from the nucleaus to the cytosol and aggregation, possibly causes, but certainly drives pathologies of motor neuron disease (MND), esp. Amyotrophic Lateral Sclerosis (ALS), as well as frontotermporal lobar degeneration. Sceond, our lab is interested in method development of frontier mass spectrometry (MS) analysis of small molecules (both targeted and discovery metabolomics) and proteins (via intact and native MS (of protein-ligand complexs) for ligand discovery and validation.
Undergraduate Teaching:
- I am coordinating and teaching in the medicinal chemistry course (MCHM3x01) running in semester 1, as well as contributing to several other courses offered by the School of Medicinal Chemistry, e.g., a module of SOMS4101 on Mass Spectrometry (focus on LCMS) in medical sciences, or lectures in the interdisciplinary medicinal chemsitry project course (MCHM3888) and pharmacology (PCOL3x12)
- I prefer students to be involved in the course through eg., flipped lecture models, and interactive sessions, rather than deliver the material without any interaction.
- The 2024 USS results for the MCHM3x01 unit I coordinate was 4.5 (out of 5), compared to school average of 4.1
Research supervision:
- At the moment, I supervise one PhD and two Honours students. Previously, I supervised to completion an Honours student (high first class), one Masters capston student, three Daylell projects (all HD). Previously, I co-supervised to completion undergraduate and postgraduate students: 3 Honours students (1st Class Honours), 4 PhD students to completion (‘17, ‘20, ‘22, '24), who all published in high impact journals (e.g., J Med Chem). Three PhD graduates took on excellent job opportunities in non-academic environments shortly after their graduation, speaking to the training they received in our lab.
I'm accepting PhD students for below projects:
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A PROTAC development platform for TDP-43 as target in neurodegenerative disease. This project focuses on the high-throughput synthesis of PROTACs targeting TDP-43, as well as compound screening to identify novel ligands for different regions (e.g., N- or C-terminus) of TDP-43. The ideal candidate brings synthetic organic chemsitry training and advanced understanding of mass spectrometry. The work will be conducted in Molecular Bioscience Building and Sydney MAss Spectrometry at Charles Perkins Centre.
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Mass Spectrometry Imaging of potential neuroprotective drug leads in the brain from Parkinson's disease and Amyotrophic Lateral Sclerosis mouse models. This project will entail a strong bioanalytical focus on metabolomics/proteomic analysis of mouse brain tissues, by using latest generation mass spectrometry housed in Sydney Mass Spectrometry. The work will be conducted in collaboration with the Brain and Mind Centre, Life Animal Services and SydneyMS at Charles Perkins Centre.
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PET-compatible bacteriophages for biodistribution studies: clinically relevant phages will be labelled with dual-function tags (fluorophore for FACS sorting, chelator for radiometal), administered in infection mouse model, and PET studies will give insight into phage biodistribution. The work is conducted in collaboation with School of Veterinary Sciences, Westmead Medical Research Institute and Charles Perkins Centre.
- Centre for Drug Discovery Innovation (DDI), USyd
- Brain and Mind Centre, USyd
- Sydney Infectious Disease (SydneyID), USyd
- ANZ Metabolomics Society (treasurer)
- Former member of the CPC EMCR Committee (06/2022-12/2023), Drug Discovery Initiative - Chair of the ECR committee (10/2020-10/2022).
- Royal Australian Chemical Institute
- International Chemical Biology Society
- Professional Development Award 2023, EMCR Initiative, Charles Perkins Centre, USyd,
- Good Mentor Award 2022, Sydney Early and Mid Career Academic Network (SEMCAN), USyd
- Archibald D. Olle Award from RACI NSW for "best paper in 2019"
- Early Career Research Excellence Award 2020 from the Drug Discovery Initiative at USyd
- CASS Foundation International Conference Travel Grant 2020
- Faculty of Medicine and Health - Boost Scheme Conference Travel support
(Yonsei University) collaboration on target validation for antimalarial and prospective anticancer agent artesunate |
| Project title | Research student |
|---|---|
| A PROTAC-BASED DEGRADATION OF TDP-43 IN THE TREATMENT AGAINST NEURODEGENERATIVE DISORDERS | Camelia BHATTACHARYYA |
Publications
Journals
- Richardson-Sanchez, T., Telfer, T., Soe, C., Nolan, K., Gotsbacher, M., Codd, R. (2024). The production of siderophore analogues using precursor-directed biosynthesis. Methods in Enzymology, 702, 121-145. [More Information]
- Ho Shon, I., Hennessy, T., Guille, J., Gotsbacher, M., Lay, A., McBride, B., Codd, R., Hogg, P. (2022). A first-in-human study of [68Ga]Ga-CDI: a positron emitting radiopharmaceutical for imaging tumour cell death. European Journal of Nuclear Medicine and Molecular Imaging, 49(12), 4037-4047. [More Information]
- Nolan, K., Font Sadurni, J., Sresutharsan, A., Gotsbacher, M., Brown, C., Ryan, R., Codd, R. (2022). Acetyl-CoA-Mediated Post-Biosynthetic Modification of Desferrioxamine B Generates N- and N-O-Acetylated Isomers Controlled by a pH Switch. ACS Chemical Biology, 17(2), 426-437. [More Information]
2024
- Richardson-Sanchez, T., Telfer, T., Soe, C., Nolan, K., Gotsbacher, M., Codd, R. (2024). The production of siderophore analogues using precursor-directed biosynthesis. Methods in Enzymology, 702, 121-145. [More Information]
2022
- Ho Shon, I., Hennessy, T., Guille, J., Gotsbacher, M., Lay, A., McBride, B., Codd, R., Hogg, P. (2022). A first-in-human study of [68Ga]Ga-CDI: a positron emitting radiopharmaceutical for imaging tumour cell death. European Journal of Nuclear Medicine and Molecular Imaging, 49(12), 4037-4047. [More Information]
- Nolan, K., Font Sadurni, J., Sresutharsan, A., Gotsbacher, M., Brown, C., Ryan, R., Codd, R. (2022). Acetyl-CoA-Mediated Post-Biosynthetic Modification of Desferrioxamine B Generates N- and N-O-Acetylated Isomers Controlled by a pH Switch. ACS Chemical Biology, 17(2), 426-437. [More Information]
- Gotsbacher, M., Codd, R. (2022). Adding a diazo-transfer reagent to culture to generate secondary metabolite probes for click chemistry. Methods in Enzymology, 665, 49-71. [More Information]
2020
- Gotsbacher, M., Codd, R. (2020). Azido-Desferrioxamine Siderophores as Functional Click-Chemistry Probes Generated in Culture upon Adding a Diazo-Transfer Reagent. ChemBioChem, 21(10), 1433-1445. [More Information]
- Roth, L., Gotsbacher, M., Codd, R. (2020). Immobilized Metal Affinity Chromatography as a Drug Discovery Platform for Metalloenzyme Inhibitors. Journal of Medicinal Chemistry, 63(20), 12116-12127. [More Information]
- Brown, C., Gotsbacher, M., Codd, R. (2020). Improved access to linear tetrameric hydroxamic acids with potential as radiochemical ligands for zirconium(IV)-89 PET imaging. Australian Journal of Chemistry, 73(10), 969-978. [More Information]
2019
- Telfer, T., Richardson-Sanchez, T., Gotsbacher, M., Nolan, K., Tieu, W., Codd, R. (2019). Analogues of desferrioxamine B (DFOB) with new properties and new functions generated using precursor-directed biosynthesis. Biometals, 32(3), 395-408. [More Information]
- Brown, C., Gotsbacher, M., Holland, J., Codd, R. (2019). Endo-Hydroxamic Acid Monomers for the Assembly of a Suite of Non-native Dimeric Macrocyclic Siderophores Using Metal-Templated Synthesis. Inorganic Chemistry, 58(20), 13591-13603. [More Information]
- Daniel, L., Gotsbacher, M., Richardson-Sanchez, T., Tieu, W., Codd, R. (2019). Exploring hydroxamic acid inhibitors of HDAC1 and HDAC2 using small molecule tools and molecular or homology modelling. Bioorganic & Medicinal Chemistry Letters, 29(18), 2581-2586. [More Information]
2018
- Codd, R., Richardson-Sanchez, T., Telfer, T., Gotsbacher, M. (2018). Advances in the Chemical Biology of Desferrioxamine B. ACS Chemical Biology, 13(1), 11-25. [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]
Selected Grants
2024
- PROTACs for TDP-43 validated by Native Mass Spectrometry and Flow Cytometry, Gotsbacher M, Faculty of Medicine and Health/Neurodrug Funding Scheme
- Biodistribution of neuroprotective metal-delivering agents and relevant metals in ALS mouse brain, Gotsbacher M, Brain and Mind Centre/Brain and Mind Research Development Grant
- A Mass Spectrometry-Based Ligand Discovery Platform, Gotsbacher M, Charles Perkins Centre/Early-Mid Career Researcher Seed Funding Grant
- Novel Ligands for TDP-43 to enable a PROTAC development platform to fight ALS, Gotsbacher M, Danon J, Kassiou M, The ALS Association/Research Grant
2023
- Professional Development Award 2023, Gotsbacher M, Charles Perkins Centre/Early to Mid-Career Researcher Professional Development
- Labelling bacteriophages for Flow Cytometry and PET Imaging, Gotsbacher M, Sydney Institute for Infectious Diseases (Sydney ID)/Sydney ID Seed Grants
In the media
C&EN article reviewing my recent work on the human protein target of artesunate, and antimalarial with promising anticancer activity: