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December 2019 Low Res.Pdf Australian Biochemist The Magazine of the Australian Society for Biochemistry and Molecular Biology Inc. December 2019, Volume 50, Number 3 VOL 50 NO 3 DECEMBER 2019 AUSTRALIAN BIOCHEMIST PAGE 1 ISSN 1443-0193 PAGE 2 AUSTRALIAN BIOCHEMIST VOL 50 NO 3 DECEMBER 2019 Table of Contents 4 Editorial Committee 5 Publications with Impact Hanging on to Heavy Metal Evolution of a New Metabolic Pathway in Parasitic Protists A Step Towards the In Vitro Cyclisation of an Unusual Glycopeptide Antibiotic BOK: It’s Not All About Death Respiratory Syncytial Virus Coopts the Mitochondria of Infected Host Cells Dancing Dustbins: Proteasome Activation Insights with Implications for Antimalarial Drug Action 14 ASBMB Education Feature Staff and Student Perceptions of Academic Expectations: How Closely Do They Align? From Little Things, Big Dreams Grow… Teaching Inside a Cell, Inside a CAVE WIL-ing Students in Science 19 SDS Page Choosing Your First Career Move After Your PhD Beyond Publication: Boosting Your Track Record for Early Career Fellowships 21 Off the Beaten Track From Benchside to Bedside – Breaking Free from Academia 23 Competition: Structure Match 24 Annual Society Conferences are Great: This Year’s ASBMB Meeting Shows Us Why 26 ASBMB Medallists and Awardees at ASBMB 2019 Conference 27 Report on ASBMB 2019 Conference 30 Intellectual Property The Usefulness of ‘Use’ Patents 32 News from the States 36 Biochemical Education: an ASBMB Special Interest Group 38 Great Expectations Meaningful Mentoring and the Path to Fulfilment 43 ASBMB Award Reports: Shimadzu Education Award Report and ASBMB Fellowships 44 ASBMB Honours Loyal Members 50 Aspiring Meeting of Young Researchers in Kuala Lumpur 51 Report on 27th FAOBMB and 44th MSBMB Conference 54 Forthcoming Meetings 55 ASBMB Annual Reports Front Cover 60 Our Sustaining Members The world’s largest model of a crystal, sodium chloride, by 64 ASBMB Council Robert Krickl, crystallographer turned science communicator. Exhibited at the 2019 European Crystallographic Meeting, 65 Directory the structure is over 3 m high and was made from about 40,000 balls and 10 km of sticks. The model shows the ionic structure that would make up a crystal of table salt 0.0000096 mm across. Photo: Gabrielle Watson. Australian Biochemist – Editor Tatiana Soares da Costa, Editorial Officer Liana Friedman © 2019 Australian Society for Biochemistry and Molecular Biology Inc. All rights reserved. VOL 50 NO 3 DECEMBER 2019 AUSTRALIAN BIOCHEMIST PAGE 3 Australian Biochemist Editorial Committee Members Editor Editorial Officer Dr Tatiana Soares da Costa Liana Friedman Department of Biochemistry and Email: [email protected] Genetics La Trobe Institute for Molecular Science La Trobe University Bundoora VIC 3086 Email: [email protected] Phone: (03) 9479 2227 Dr Doug Fairlie Dr Sarah Hennebry Olivia Newton-John Cancer FPA Patent Attorneys Research Institute and La Trobe 101 Collins Street University Melbourne VIC 3000 Heidelberg VIC 3084 Email: sarah.hennebry@ Email: [email protected] fpapatents.com Phone: (03) 9496 9369 Phone: (03) 9288 1213 Joe Kaczmarski Associate Professor Tracey Kuit Research School of Chemistry School of Chemistry and Molecular Australian National University Bioscience Canberra ACT 0200 University of Wollongong Email: joe.kaczmarski@ Wollongong NSW 2522 anu.edu.au Email: [email protected] Phone: (02) 4221 4916 Dr Erinna Lee Dr Nirma Samarawickrema La Trobe Institute for Molecular Department of Biochemistry and Science and Olivia Newton-John Molecular Biology Cancer Research Institute Monash University Heidelberg VIC 3084 Clayton VIC 3800 Email: [email protected] Email: nirma.samarawickrema@ Phone: (03) 9496 9369 monash.edu Phone: (03) 9902 0295 Dr Gabrielle Watson Monash Biomedicine Discovery Institute Monash University Clayton VIC 3800 Email: gabrielle.watson@ monash.edu Phone: (03) 9902 9227 PAGE 4 AUSTRALIAN BIOCHEMIST VOL 50 NO 3 DECEMBER 2019 Publications with Impact Publications with Impact profiles recent, high impact publications by ASBMB members. These short summaries showcase some of the latest research by presenting the work in a brief but accessible manner. If your work has recently been published in a high profile journal, please contact [email protected] Hanging on to Heavy Metal De Luca A#, Parker LJ#, Ang WH, Rodolfo C, Gabbarini V, Hancock NC, Palone F, Mazzetti AP, Menin L, Morton CJ, Parker MW*, Lo Bello M, Dyson PJ*. A structure-based mechanism of cisplatin resistance mediated by glutathione transferase P1-1. Proc Natl Acad Sci USA 2019;116(28):13943–13951. #Equal first authors *Corresponding authors: [email protected], [email protected] “On Aussie soil… the GST remains a three letter Despite first being used in the 1970s, cisplatin (cis- swear word” but is vital for our health! GSTs are diamminedichloridoplatinum(II), CDDP) is still one of the dimeric proteins that belong to a superfamily most successful anti-cancer agents employed today and of multifunctional enzymes involved in cellular is first-line treatment for a wide range of solid tumours. detoxification of many potentially cytotoxic It is well established that the mechanism of CDDP molecules through conjugation with the nucleophilic involves the formation of intra-strand crosslinks in DNA, thiol containing compound glutathione (GSH). blocking genome replication and transcription, leading After catalytic conjugation of GSH to the targeted to apoptosis. In this context, the DNA-binding proteins compound, the product is recognised by specific involved in these cellular processes play a fundamental cellular export machinery and expelled from the role in the mechanism of CDDP activity and have been cell. Clearly, this protective mechanism can be the subject of intense study. However, the mode of tumour misused by malignant cells to protect them from targeting and other molecular interactions that the active chemotherapeutic agents in exactly the same way platinum species experience are less well understood. that it protects normal cells. Indeed, the most highly Only 5–10% of intracellular platinum is associated with expressed isoforms of human GSTs, the GST Pi class the DNA fraction; after CDDP enters the cell, the reduced enzymes, have been found to be overexpressed in concentration of chloride ions in the cytoplasm results several solid tumours and in different tumour cell in the rapid formation of mono- and di-aquo species, lines resistant to anti-cancer drug treatment directly in which one or two chloride ions are substituted by linking GST levels with drug resistance. In exploring water molecules. It is these new species that are highly the role of GST in resistance to cancer therapy, the reactive towards a number of nucleophilic compounds Parker lab and collaborators in Switzerland and Italy including RNA, DNA and thiols found both in thiol- have found an unexpected alternative mechanism containing proteins (i.e. any protein with a free cysteine through which GST enzymes inactivate some anti- residue) and small molecule thiol compounds like GSH. cancer agents. Historically, it has been suggested that intracellular CDDP is complexed with GSH in a GST-catalysed reaction. Several lines of supporting evidence for this model exist, with GSH depletion shown to sensitise formerly CDDP resistant cell lines and simultaneous administration of GSH and CDDP inducing CDDP resistance in human lung carcinoma cells. We employed a combination of structural biology, enzymology and cell biology to explore the details of GST Pi activity in the fate of cellular CDDP. To our surprise, it became clear that CDDP is not a substrate for the GSH- transferase activity of GST Pi. Instead, we showed that the free cysteine thiol groups of the enzyme, specifically the side-chains of cysteine 101 that lie in the GST dimer interface, are particularly competent at binding platinum species and sequestering them within the protein. This The structure of GST Pi complexed with glutathione and sponge-like activity for GST in removing the reactive platinum after exposure to cisplatin. The platinum (purple metal species occurs both in vitro and in the context of live spheres) is found associated with cysteine 101 in the tumour cells, is a novel protective mechanism for removing dimer interface. cytotoxic heavy metals. The relative contribution of this VOL 50 NO 3 DECEMBER 2019 AUSTRALIAN BIOCHEMIST PAGE 5 Publications with Impact sequestration to GST’s role in defending cells from toxic metal species remains to be fully determined, although we have also demonstrated that the mechanism extends to other metals such as ruthenium and the metalloid arsenic. Like GST, arsenicals have dubious history, but paradoxically are used as drugs for the treatment of acute promyelocytic leukemia. Craig Morton and Michael Parker Bio21 Institute, University of Melbourne and St Vincent’s Institute Craig Morton (left) and Michael Parker ponder their sequestering options. Evolution of a New Metabolic Pathway in Parasitic Protists Sernee MF#, Ralton JE#, Nero TL, Sobala JF, Kloehn J, Vieira-Lara M, Cobbold SA, Stanton L, Pires DEV, Hanssen E, Males A, Ward T, Bastidas LM, van der Peet PL, Parker MW, Ascher DB, Williams SJ, Davies GJ, McConville MJ*. A family of dual-activity glycosyltransferase- phosphorylases mediates mannogen turnover and virulence in Leishmania parasites. Cell Host Microbe 2019;26(3):385–399. #Equal first authors *Corresponding author: [email protected] Understanding how pathogens invade and survive immune response by invading
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