Australian Biochemist
The Magazine of the Australian Society for Biochemistry and Molecular Biology Inc. April 2020, Volume 51, Number 1
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 1 ISSN 1443-0193 Table of Contents
3 Editorial Committee 4 From the President 7 Publications with Impact The Black Sheep of the Family Balancing the Batteries: the Importance of Coordinated Mitochondrial Protein Synthesis for Energy Production Plexin B2: Putting the Trash Out Targeting the Gut Epithelium to Manage Obesity Advanced Imaging Tips T Cell Target Recognition on its Head Cellular Couriers of Oncogenic Cargo 16 ASBMB Education Feature Improving Learning Outcomes from Undergraduate Research Experiences Teaching Students to Work Effectively in a Group Harnessing Interdisciplinary Education in Biochemistry and Molecular Biology So, How Did I Do? Using Student Self-assessment to Steer Feedback 21 SDS Page From Undergrad to Postgrad: How to Survive the First Year of Your PhD 22 Competition: Word Search 23 ASBMB Medallist and Awardee Profiles 28 ASBMB Fellowship Profiles 30 Science meets Parliament 2019 Report 32 Sydney Protein Group: an ASBMB Special Interest Group 33 Election of Council 2021 34 Biochemistry on Stage 36 Great Expectations Unexpected Journeys Through Different Research Lands and Scientific Families 40 Boomerang Award Report 41 Intellectual Property Artificial Intelligence in Medicine – What is Patentable? 43 Science Teachers’ Association of Victoria – Science Talent Search 44 Australia Day Honour for ASBMB Member 45 In Memoriam 49 Our Sustaining Members 52 ASBMB Council 53 Directory
Front Cover Artist’s rendition of the Golgi apparatus. By Chloe Gleeson.
Australian Biochemist – Editor Tatiana Soares da Costa, Editorial Officer Liana Friedman © 2020 Australian Society for Biochemistry and Molecular Biology Inc. All rights reserved.
PAGE 2 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Australian Biochemist Editorial Committee
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
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 3 From the President
Dear ASBMB Members
This message is to let you know that, due to the COVID-19 pandemic, we have decided to postpone ComBio2020 until 2022. The conference will be held at the Melbourne Convention and Exhibition Centre, with registration starting in late afternoon of Tuesday 27 September, and the full program running from Wednesday 28 September through to Friday 30 September 2022. Thanks to our great organising committee, the program is already very advanced with most of the symposium sessions, chairs and invited speakers in place. See the ComBio2022 website for more information.
Between now and then, we will endeavour to keep our scientific community invigorated with online forums and other communications. We welcome suggestions!
Stay safe and flatten the curve.
Jackie Wilce (Chair, ComBio2022) and Joel Mackay (President, ASBMB)
Well, the start of 2020 has been quite something. Through Twitter, I have now seen photos of more of my science colleagues’ pets than ever before, not to mention their spare rooms!
It would certainly be fascinating to fast-forward to the and the conference organiser, Sally Jay, have been end of the year and see where the world lies. Over that doing a magnificent job over the last couple of years time and in the longer term, it will also be interesting in assembling the program and everything else that is to see whether there is any substantial shift in the required to organise a major meeting. To make sure attitude of both the government and the public towards that we don’t squander all of that effort, we made the basic, biomedical and other research. Biochemistry decision to postpone ComBio2020 to 27–30 September and molecular biology are key disciplines in the race 2022. The good news is that we’ve never been so far to unlock the secrets of COVID-19 and to generate advanced in our preparations for a ComBio! Several vaccines and effective treatments. Scientists have questions arise from this decision: probably never had quite such an urgent opportunity to be near the front of people’s consciousness, not to Is there going to be an ASBMB event this year? mention the opportunity to be the saviours. I have seen At this stage, we are not planning any face-to-face a number of comparisons drawn between this crisis and meetings. However, because one of the main functions the issue of climate change, so it will be particularly of ASBMB is to bring members together for discipline- interesting to see whether this situation has an impact related discussions, we would like to do something. on the climate debate in the longer term. Currently, we are considering what the best option would be. One option we are exploring is to hold an Conferences online symposium dedicated to the question: How have In this environment, the primary subject of discussion you dealt with the transition to online teaching – what on the ASBMB Executive and Council has been around has worked and what hasn’t? Another might be to have the issue of what to do about the ComBio2020 meeting. something more social, like an ASBMB online trivia Conference Chair, Jackie Wilce, and Program Chair, event, for example. A third could be to host an online Mark Hulett, together with their organising committee research-focused meeting; I have already seen at least
PAGE 4 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 From the President a couple of organisations advertise such meetings. This Other matters would also give us a chance to showcase the research Over the last year, Council has developed better of our 2020 award winners. Finally, if restrictions on guidelines for our State Representatives and our meeting in person ease up towards the end of the year, Special Interest Groups so that we can better serve the we might be able to move relatively quickly to host a membership, and give the State Representatives more couple of smaller local meetings that require less voice in shaping the Society. The website has also been organisation (and are consequently cheaper). A meeting updated and refreshed. of this type might also allow use to showcase the work In the coming year, I am keen to address several of the 2020 ASBMB award winners. We welcome any questions: other suggestions. • Should we champion a dedicated Education symposium? What is ASBMB now planning for 2021? • Should we reactivate an annual Heads of discipline Our plans for 2021 are to co-host the FAOBMB meeting to discuss shared issues and bring the Congress in Christchurch in November and to host an academic Biochemistry and Molecular Biology extended East Coast Protein Meeting in July. At the community closer together? moment, we still anticipate that these events will take • How can we strengthen our contribution to science place and we cross our collective fingers that they will advocacy? be able to be run successfully. Please let me know if there are other issues that you think should be considered by the ASBMB. What about 2023? In our original plans, ComBio2022 was scheduled to Council be held in Canberra. However, the Society recently Finally, I would like to thank all of the members of the decided to hold an ASBMB-only meeting in odd years. ASBMB Council for their work for the Society. Briony We have resolved to pursue that option for 2023. We Forbes as Secretary (being succeeded by Dominic Ng), are currently in discussions about potential organisers Marc Kvansakul with his hand on the purse strings, and and potential venues for that meeting. Jacqui Matthews as President Elect. Tatiana Soares da Costa is doing a great job as our magazine Editor, Awards and is also championing the ASBMB Twitter feed I’d like to congratulate our 2020 ASBMB award winners: @ITSASBMB, ComBio Twitter feed @ComBio2022 Professor Trevor Lithgow, Monash University (Lemberg and ComBio on Facebook. Please let her know if you Medal); Professor Colin Jackson, Australian National have your own Twitter account so that she can follow University (Shimadzu Research Medal); Professor Si it and make sure you follow us too! I would also like Ming Man, Australian National University (Eppendorf to acknowledge the fantastic support we get from Sally Edman ECR Award); Dr Nirma Samarawickrema, and Chris Jay (National Office) and Liana Friedman Monash University (SDR Scientific Education Award); (Editorial Officer and Webmaster). Dr Matthew Doyle, National Institutes of Health, Bethesda (Boomerang Award); and the ASBMB I even managed to get though to the end of this piece Fellowship recipients, Dr Amy Baxter, La Trobe Institute without mentioning toilet paper – oh, drat! for Molecular Science (the Fred Collins Award); Dr Steffi Cheung, University of Melbourne; Dr Mengjie Hu, Joel Mackay University of Melbourne; Anukriti Mathur, Australian President, ASBMB National University. The Executive are currently considering the best mechanism to allow our award winners to showcase their work – in lieu of the plan to have them speak at ComBio2020. Stay tuned for more information. And of course, don’t forget the ASBMB awards for 2021 – think about getting someone to nominate you or encourage a colleague to let you nominate them. We would particularly like female members to consider putting themselves forward – it’s well known that women are less likely to consider themselves for such awards and we would encourage people to think about this and try to help us reverse that long-time trend!
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 5 MADE IN EUROPE
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02 9575 7512 [email protected] www.capellascience.com.au PAGE 6 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 MADE IN EUROPE Publications with Impact ULT FREEZERS Publications with Impact profiles recent, high impact publications by ASBMB members. Dual-independent Auto-cascade 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 compressor system published in a high profile journal, please contact us at [email protected].
The Black Sheep of the Family
Vuckovic Z#, Gentry PR#, Berizzi AE, Hirata K, Varghese S, Thompson G, van der Westhuizen ET, Burger WAC, Rahmani R, Valant C, Langmead CJ, Lindsley CW, Baell JB, Tobin AB, Sexton PM,
Christopoulos A*, Thal DM*. Crystal structure of the M5 muscarinic acetylcholine receptor. Proc Natl Acad Sci USA 2019;116(51):26001–26007. #Equal contributors *Corresponding authors: [email protected], [email protected]
The muscarinic acetylcholine receptors (mAChRs) III
are a five-membered family (M1–M5) of Class A G VI E/P179-4 ECL1 240 | 50mm boxes protein-coupled receptors (GPCRs) that, together
with the nicotinic acetylcholine receptors, mediate ECL2 G/D181-2 the actions of the neurotransmitter acetylcholine 320 | 50mm boxes E182-1 throughout the human body. Historically, these receptors are well characterised with the first C1830 480 | 50mm boxes +6 INTRODUCTORY studies dating back to the mid 1980s. However, the S189 Y/Q184+1 Y/R95ECL1 M5 mAChR has been the black sheep of the family: it was the last to be cloned, the last to be officially Y902.64 OFFER V II classified as a bona fide mAChR in 1998 and it is 2.61 Special price on Y87 the least studied mAChR. This lack of attention N/S4656.58 racks, boxes has extended to the determination of its atomic T/I912.65
& tubes. structure, as the structures of the M1–M4 mAChRs I have been previously determined. In collaboration W4777.35 T/H4787.36 P/K470ECL3 N/V4747.32 with laboratories from Monash University, Vanderbilt M2R•NMS VI VII M5R•tiotropium University, and the University of Glasgow, the labs A/D4696.62 of David Thal and Arthur Christopoulos at Monash ECL3
University were able to determine the M5 mAChR structure, completing the collection of structures Comparison of residues lining the extracellular
for this therapeutically important class of GPCRs. regions of the M2 and M5 mAChR. Graphic touch-screen Data-logger/ 48 hour battery Key-locked The mAChRs are involved in a wide range of Residues from the M mAChR are shown in dark blue and controller USB port back up power switch 2 physiological processes in both the central nervous M5 mAChR in green. Conserved residues are labelled system (CNS) and the periphery. As such, they have black, and non-conserved residues have coloured labels long been valued as drug targets for the design based on receptor subtype. Chimeric swaps of the ECL
of novel therapeutics. The M1 and M4 subtypes, in regions between the M2 and M5 mAChRs results in a Castors/ CFC-free injected Low-noise CFC/HCFC-free particular, have been implicated in Alzheimer’s disease, switch in the sensitivity of subtype selective allosteric levelling feet insulation 56 db(A) refrigerant Parkinson’s disease, schizophrenia and gastrointestinal modulators. Reproduced under a CC BY-NC-ND license.
functions. Although less is known about the M5 mAChR,
in part due to the difficulty of designing tool compounds Despite such promising data, further study of the M5 OPTIONS that are selective for each mAChR subtype, knockout mAChR has been hindered by a lack of small molecular M5 mAChR mice exhibit attenuated reward-seeking ligands that selectivity target the receptor. The design Electronic/magnetic Chart 5x internal CO2/LN2 GSM phone Underbench models behaviour to drugs of addiction, such as cocaine and of such selective ligands has proven challenging, door lock recorder doors/shelves back-up alarm also available morphine. Furthermore, our collaborators at Vanderbilt due to the highly conserved acetylcholine orthosteric- University were the first to discover a subtype-selective binding site combined with a lack of detailed structural
negative allosteric modulator of the M5 mAChR that, information for all five mAChR subtypes. Using lipidic partly through collaboration with our groups, was shown cubic phase crystallography, we were able to determine
to attenuate ethanol-seeking behaviour and oxycodone a high-resolution structure of the M5 mAChR bound to 02 9575 7512 self-administration in rats. Collectively, these studies the clinically used antagonist tiotropium. A comparison
suggest that selective antagonism of the M5 mAChR is of all five mAChR subtypes showed a nearly identical [email protected] a potential treatment for drugs of addiction. orthosteric-binding site. However, comparison of www.capellascience.com.au VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 7 Publications with Impact
the extracellular loop (ECL) regions revealed subtle differences that could potentially mediate the selectivity of orthosteric and allosteric ligands. To test this hypothesis, we designed chimeric receptors with ECL
regions swapped between the M2 and M5 mAChRs. In pharmacological experiments with the chimeric receptors, we were able to completely switch the sensitivity of an allosteric modulator that is selective for
the M2 versus the M5 mAChR, and vice versa. These findings, together with a now completed set of mAChR structures, open the door for future structure-based design of selective drugs. David Thal Monash Institute of Pharmaceutical Sciences From left: Wessel Burger, Geoff Thompson, Monash University Celine Valant, Emma van der Westhuizen, David Thal, Ziva Vuckovic and Arthur Christopoulos.
Balancing the Batteries: the Importance of Coordinated Mitochondrial Protein Synthesis for Energy Production
Rudler DL# , Hughes LA#, Perks KL, Richman TR, Kuznetsova K, Ermer JA, Abudulai LN, Shearwood A-MJ, Viola HM, Hool LC, Siira SJ, Rackham O, Filipovska A*. Fidelity of translation initiation is required for coordinated respiratory complex assembly. Sci Adv 2019;5(12):eaay2118. #Equal contributors *Corresponding author: [email protected]
The circular mitochondrial genome is a relic of lack conventional 5′ and 3′ untranslated regions and do a chance encounter two billion years ago that set not have Shine-Dalgarno sequences found in bacterial the scene for multicellular life. The endosymbiotic mRNAs. Since mitochondrial mRNAs lack these flanking union between an ancestral alpha-proteobacterium sequences, it is still not clear how mitoribosomes dock and a proto-eukaryotic cell created mitochondria, and recognise their start codons, suggesting that the energy producing organelles within eukaryotic alternative mechanisms exist that translate leaderless cells. Our second genome, the mitochondrial mRNAs. It is likely that mS39 (PTCD3), a mitoribosomal DNA (mtDNA), encodes a small subset of proteins protein we identified and characterised in 2009, which are components of the molecular machines interacts with the incoming mRNAs and facilitates their that produce energy, known as the oxidative recruitment to the small subunit. However, it was not phosphorylation (OXPHOS) system. mtDNA- clear which factors enabled mitoribosomes to initiate encoded transcripts and proteins are expressed translation in the absence of untranslated regions in the and synthesised inside the mitochondrial matrix. mitochondrial mRNAs. Mitochondria import all the proteins they require for Protein synthesis in mitochondria is overall similar mtDNA expression and protein synthesis, including to that of bacteria, beginning with an initiation phase, nuclear-encoded mitochondrial ribosomal proteins followed by polypeptide elongation, termination and and translation factors that are essential for ribosome recycling. Translation initiation in mitochondria the production of the mtDNA-encoded proteins. shares similarities with prokaryotic systems, such as Therefore, both nuclear and mitochondrial gene the formation of a ternary complex of fMet-tRNAMet, expression require tight coordination to enable mRNA and the small ribosomal subunit, but differs in correct assembly and function of the electron the requirements for initiation factors. Bacteria have transport chain. However, the factors mediating this three initiation factors whose roles are well understood, coordination are not fully understood. whereas mitochondria have two initiation factors, MTIF2 Mitochondrial protein synthesis in animals is unique that closes the decoding centre and stabilises the in that the ribosomes have acquired mitochondria- binding of the fMet-tRNAMet to the leaderless mRNAs, specific proteins and translate unusual mRNAs which and MTIF3 whose role was not clear.
PAGE 8 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Publications with Impact
A B Wild type MTIF3 Pre-initiation complex MTIF3 formation proofreading mRNA tRNAMet 28S
Met Met
Rate limiting Protein synthesis MTIF3 Met Met MTIF3 knockout
Met MTIF2 GTP Translation initiation complex Overloaded Degradation Met stalling
GDP Met 55S Translation
39S Met Met
Increased protein synthesis
The mechanism of translation initiation. A. MTIF3 prevents the translation initiation complex formation if it is bound by a tRNA in the absence of mRNA. Only small ribosomal subunits that have bound mRNA before the recruitment of tRNA and MTIF2 are able to proceed from translation initiation to elongation. B. MTIF3 performs molecular proofreading; in its absence, translation initiation proceeds at an accelerated rate but at the expense of fidelity. When fidelity of initiation is compromised, initiation complexes can stall at the start of mRNAs, leaving the remainder of the mRNA prone to degradation.
We knocked out the Mtif3 gene in mice to show that reduces specific respiratory complexes as the ratios this protein is essential for embryo development. Heart- of proteins are disturbed; this compromises OXPHOS and skeletal muscle-specific loss of MTIF3 caused function and causes dilated cardiomyopathy. Our dilated cardiomyopathy. We identified increased but findings demonstrate that the initiation of mitochondrial uncoordinated mitochondrial protein synthesis in protein synthesis fine-tunes the assembly of respiratory mice lacking MTIF3, which resulted in loss of specific complexes, as required for optimal energy production. respiratory complexes. Our proteomic analyses Aleksandra Filipovska showed that coordinated assembly of OXPHOS Harry Perkins Institute of Medical Research complexes requires stoichiometric levels of nuclearly- and mitochondrially-encoded protein subunits in vivo. Ribosome profiling and transcriptomic analyses revealed that MTIF3 is required for recognition and regulation of translation initiation of mitochondrial mRNAs, but not dissociation of the ribosome subunits. Without the molecular proofreading steps performed by MTIF3, translation initiation proceeds at an accelerated rate but at the expense of fidelity. When fidelity of initiation is compromised, initiation complexes can stall at the 5′ ends of mRNAs, leaving the remainder of the mRNA prone to degradation by 3′–5′ exoribonucleases. Therefore, MTIF3 has a role in proofreading during mitochondrial translation initiation and can destabilise the initiation complex in the absence of mRNA binding to ensure correct assembly of all the components required for protein synthesis. From left: Oliver Rackham, Laetitia Hughes, Danielle We established that MTIF3 is essential for coordinated Rudler and Aleksandra Filipovska led the project at the translation initiation and that its loss opens the Harry Perkins Institute of Medical Research and Curtin floodgates of mitochondrial translation but surprisingly Health Innovation Research Institute, Curtin University.
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 9 Publications with Impact
Plexin B2: Putting the Trash Out
Atkin-Smith GK, Miles MA, Tixeira R, Lay FT, Duan M, Hawkins CJ, Phan TK, Paone S, Mathivanan S, Hulett MD, Chen W, Poon IKH*. Plexin B2 is a regulator of monocyte apoptotic cell disassembly. Cell Rep 2019;29(7):1821–1831.e3. *Corresponding author: [email protected]
Every week, we gather our household rubbish in preparation for bin day. Through garbage bags and bins, our waste is stacked in an organised fashion for the swift removal by passing garbage trucks. Similarly, every minute within the human body, our waste consisting of millions of dying cells is being prepared for its efficient removal by the garbage trucks of the body, i.e. phagocytes. Although the clearance of dead cells is a well-studied concept, how the final moments of a cell’s death impacts its removal has been overlooked. For example, it was uncertain if a similar packaging mechanism to our garbage bags occurs and contributes to the rapid removal of dying cells. In our recent study in Cell Reports, we identified a novel role of the membrane receptor Plexin B2 in aiding the packaging of dying Cartoon of the role of Plexin B2 during cells to assist their efficient clearance. Following the initiation of apoptosis, apoptotic cells can monocyte apoptosis and clearance by phagocytes. undergo a number of morphological changes, a process monocytes and identified the membrane receptor Plexin called apoptotic cell disassembly, to help the packaging B2 to be enriched in apoptotic bodies. and fragmentation of dying cells. These morphological Plexin B2 is best known for its role in aiding cytoskeletal changes include apoptotic membrane blebbing, thin reorganisation such as that occurring in neuronal apoptotic protrusion formation and the generation of guidance. However, of the broad Plexin protein family, large extracellular vesicles called apoptotic bodies. Plexin B2 is not well characterised and has no previously Previously, we identified a new type of membrane known functions in cell death processes. Therefore, we protrusion generated by apoptotic monocytes coined examined the role of Plexin B2 during apoptosis and beaded apoptopodia that consist of a distinct ‘beads- found that Plexin B2 was cleaved by caspase 3 and 7; on-a-string’ structure (Atkin-Smith et al. 2014 Nature further, the C-terminal fragment of Plexin B2 was highly Communications). Notably, beaded apoptopodia enriched in the apoptotic bodies of THP1 monocytes. fragment through a segmentation-like event and release Excitingly, Plexin B2 now represents a novel caspase 3/7 an abundance of apoptotic bodies. To investigate the target and one of the few known markers of monocyte molecular control underpinning monocyte beaded apoptotic bodies. apoptopodia formation, we performed proteomic To determine whether Plexin B2 could also aid the analysis on isolated apoptotic bodies from human THP1 disassembly of apoptotic monocytes, we targeted the expression of Plexin B2 by a CRISPR/Cas9-based approach and monitored the disassembly of Plexin B2-deficient apoptotic cells by time-lapse microscopy. Interestingly, lack of Plexin B2 significantly impaired the formation of beaded apoptopodia and the sequential fragmentation into apoptotic bodies. Furthermore, when incubated with either professional or non-professional phagocytes, lack of Plexin B2 significantly impaired the clearance of apoptotic monocytes. Together, this study identified Plexin B2 as the first positive regulator of monocyte beaded apoptopodia and found it to be required for packaging apoptotic monocytes into apoptotic bodies for the efficient removal by phagocytes. Georgia Atkin-Smith and Ivan Poon La Trobe Institute for Molecular Science Georgia Atkin-Smith and Ivan Poon. La Trobe University
PAGE 10 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Publications with Impact
Targeting the Gut Epithelium to Manage Obesity
Dávalos-Salas M, Montgomery MK, Reehorst CM, Nightingale R, Ng I, Anderton H, Al-Obaidi S, Lesmana A, Scott CM, Ioannidis P, Kalra H, Keerthikumar S, Tögel L, Rigopoulos A, Gong SJ, Williams DS, Yoganantharaja P, Bell-Anderson K, Mathivanan S, Gibert Y, Hiebert S, Scott AM, Watt MJ*, Mariadason JM*. Deletion of intestinal Hdac3 remodels the lipidome of enterocytes and protects mice from diet-induced obesity. Nat Commun 2019;10(1):5291. *Corresponding authors: [email protected], [email protected]
The Problem repression’ of the PPAR family of transcription factors, The latest Australian Bureau of Statistics National particularly PPARa. The increased levels of lipid Health Survey (2018) revealed that two thirds of oxidation genes were associated with an increased rate Australian adults and one quarter of children aged 5–17 of lipid oxidation and, in turn, reduced levels of cellular were overweight or obese. Obesity is strongly linked lipids in the intestinal epithelium of Hdac3 knockout to the development of multiple comorbidities including mice. Importantly, this translated into lower levels of cardiovascular disease, high blood pressure, Type 2 circulating triglycerides, which we propose manifests diabetes (T2D), insulin resistance (IR) and metabolic in the leaner phenotype of these mice over time. We syndrome (1–3), which has a major impact on Australia’s were subsequently able to demonstrate that the gene economy. It is estimated that the combined (indirect expression changes induced by Hdac3 deletion could and direct) annual cost of treating obesity-related be reproduced, at least in part, using a small molecule comorbidities is now approaching AUD $10 billion (4). inhibitor of HDAC3 activity (RGFP966), unveiling a While lifestyle changes such as diet and exercise are potential new pharmacological strategy for managing clearly effective in reducing and preventing obesity, obesity. these are often difficult to maintain. New approaches for preventing and managing obesity are therefore clearly A Glimpse into the Future needed. These findings establish a central role for HDAC3 in coordinating PPAR-regulated expression of lipid A New Discovery oxidation genes in the intestinal epithelium and Our group recently discovered that ablation of the consequently the rate of lipid metabolism in this histone deacetylase 3 (HDAC3) protein, specifically in tissue, thus identifying intestinal HDAC3 as a potential the intestinal epithelium, protects mice against diet- therapeutic target for preventing obesity and related induced obesity (5). Investigation of the mechanisms diseases. Essential to this will be the development driving this effect revealed that deletion of the Hdac3 of innovative drug delivery strategies, which enable gene induced an increase in expression of lipid oxidation HDAC3 inhibitors to be locally delivered and retained in genes in intestinal epithelial cells, which was due to ‘de- the intestinal epithelium.
Proposed model of fatty acid metabolism in intestinal epithelial cells in (A) Hdac3WT and (B) Hdac3IKO mice. Dietary lipids (blue) enter intestinal epithelial cells via the apical membrane. Within the cell, fatty acids undergo multiple fates including (1) metabolism via b-oxidation in the mitochondria and peroxisomes, and (2) packaging into chylomicrons (ChM, yellow circles) for shipment to peripheral organs. In wild-type mice (A), expression of b-oxidation genes are repressed by HDAC3, and the rate of b-oxidation is low. Consequently, the majority of fatty acids are packaged into ChM for export. Comparatively, the loss of HDAC3 (B) results in constitutive expression of b-oxidation genes and increased rate of fatty acid oxidation. This in turn leads to lower levels of fatty acids being available for packaging into ChM and export. VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 11 Publications with Impact
References 1. Cani PD, Delzenne NM, Amar J, Burcelin R (2008) Pathol Biol 56(5):305–309. 2. Canfora EE, Meex RCR, Venema K, Blaak EE (2019) Nat Rev Endocrinol 15(5):261–273. 3. Reviewed in https://www.who.int/en/news-room/ fact-sheets/detail/obesity-and-overweight 4. Reviewed in PwC report: Weighing the cost of obesity: a case for action, 2015. 5. Dávalos-Salas M, et al. (2019) Nat Commun 10(1):5291. Mercedes Dávalos-Salas and John Mariadason Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine Members of John Mariadason’s group. Advanced Imaging Tips T Cell Target Recognition on its Head
Le Nours J#, Gherardin NA#, Ramarathinam SH, Awad W, Wiede F, Gully BS, Khandokar Y, Praveena T, Wubben JM, Sandow JJ, Webb AI, von Borstel A, Rice MT, Redmond SJ, Seneviratna R, Sandoval-Romero ML, Li S, Souter MNT, Eckle SBG, Corbett AJ, Reid HH, Liu L, Fairlie DP, Giles EM, Westall GP, Tothill RW, Davey MS, Berry R, Tiganis T, McCluskey J, Pellicci DG, Purcell AW, Uldrich AP, Godfrey DI*, Rossjohn J*. A class of gd T cell receptors recognize the underside of the antigen-presenting molecule MR1. Science 2019;366(6472):1522–1527. #Equal contributors *Corresponding authors: [email protected], [email protected]
T cells represent a key component of our immune and determined the crystal structure of a gd T cell system and play a critical role in protecting us receptor (TCR) in complex with the MR1 molecule, against harmful pathogens, like viruses and which completely redefined the parameters of TCR bacteria, and cancers. The more we understand recognition determinants. how they recognise, interact with and even kill During the course of evolution, the immune system of infected or cancer cells, the closer we move to vertebrates has consistently and remarkably adapted developing therapies and treatments for a range to protect itself from pathogens such as bacteria, of conditions. The research groups of Jamie yeast, viruses and parasites, to enable reproduction Rossjohn (Biomedicine Discovery Institute, Monash and ensuring the survival of the species. To achieve University) and Dale Godfrey (Peter Doherty Institute, this, the immune system of vertebrates comprises a University of Melbourne) reported the MHC-I like complex network of cells, organs, tissues, proteins and molecule, MR1, as a ligand for human gd T cells molecules that collectively constitutes the primary line of defence against various pathogens. In particular, T cells represent a key component of our immune system. They express cell surface receptors called TCRs. TCRs have the ability to recognise pathogen-derived molecules termed antigens (Ags). These encompass proteins, lipids, metabolites and carbohydrates, which are presented to the major histocompatibility complex (MHC). In collaboration with the Godfrey laboratory, our research is primarily focussed on understanding the mechanism that underpins this recognition event at the cellular and molecular level. T cells can be divided into two main groups based on the genes that encode their TCRs, namely ab and gd T cells. Over the last decades, Members of the Biomedicine Discovery Institute, studies in T cell-mediated immunity have focused on Monash University, involved in the study, from left: understanding the presentation of peptide-derived Ags Jérôme Le Nours, Benjamin Gully and Wael Awad. by the MHC, and their molecular recognition by ab
PAGE 12 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Publications with Impact
TCRs. However, ab and gd T cells can respond to other classes of Ags associated with both protective and aberrant immunity; our understanding of non-peptide- centric ab and gd T cell mediated immunity in humans is still poorly understood. In this recent study, we have identified a novel target molecule for gd T cells, known as the MHC-related 1 molecule (MR1). MR1 shares structural similarities with the classical MHC molecules, although it has evolved to accommodate a chemically distinct class of Ags, namely microbial vitamin B-derived metabolites. This first major discovery suggests that gd T cells may play a role in infection via this pathway, and reveals MR1 as a potential novel target for manipulating this poorly characterised class of T cells. Further, using X-ray crystallography, we determined the structure of the first ternary complex of a human gd TCR bound to MR1. Our structural studies led to a very intriguing result whereby the gd TCR was bound underneath the MR1- Ag binding groove for recognition, contrasting with the prevailing view that T cell receptors invariably sat atop the MHC and MHC-like molecules for recognition. This discovery has redefined what we thought we knew about T cell recognition for the past 20 years and represents a major advance in the field of T cell biology. The gd T cells represent an important population in various types of immunity, including tumor and microbial immunity. These new insights will have major implications for our understanding of gd T cell biology and should ultimately give rise to new approaches to target this broader family of cells in both infectious and non-infectious diseases. A. Crystal structure of the G7 gdTCR-MR1-5-OP-RU Jérôme Le Nours ternary complex. Biomedicine Discovery Institute B. Small angle X-ray scattering (SAXS) of the ternary Department of Biochemistry and Molecular Biology complex. Monash University
Cellular Couriers of Oncogenic Cargo
Kalra H, Gangoda L, Fonseka P, Chitti SV, Liem M, Keerthikumar S, Samuel M, Boukouris S, Al Saffar H, Collins C, Adda CG, Ang CS, Mathivanan S*. Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells. J Extracell Vesicles 2019;8:1690217. *Corresponding author: [email protected]
β-catenin is a highly conserved multifunctional Among these, mutations in β-catenin, especially in protein that has been implicated in canonical the phosphorylation sites that regulate the stability Wnt signalling pathway and cell adhesion. Wnt (S33, S37, T41, S45), can lead to the constitutive signalling is an evolutionarily conserved pathway activation of Wnt signalling pathway thereby that plays a fundamental role during embryonic resulting in increased cell proliferation. development and tissue homeostasis. However, Extracellular vesicles (EVs) are considered mediators aberrant Wnt signalling resulting from mutations of intercellular communication both at local and distant of key genes including APC and β-catenin can lead sites. EVs mediate cell-to-cell communication through to a wide variety of human diseases. It has been the horizontal transfer of cargo molecules including known for some time that approximately 93% of all proteins and nucleic acids. It is now well established colorectal cancer (CRC) have mutations in at least that EVs regulate various pathophysiological processes one gene implicated in the Wnt signalling pathway. in favour of cancer progression, including remodelling
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 13 Publications with Impact
Extracellular vesicles can mediate the intercellular transfer of oncogenic cargo including mutant β-catenin and aid in the increase of Wnt signalling, proliferation, migration and tumour burden. the tumour microenvironment, immune evasion, genetic and behavioral variations leading to intratumour coagulation, vascular leakiness, establishing pre- heterogeneity. Therefore, different clonal subpopulations metastatic niche, tropism for metastasis, transfer of bearing different mutational loads could potentially chemoresistance and metastasis. In this study, we interact with each other and with normal and stromal examined whether the oncogenic mutant β-catenin, cells via EVs. Hence, several groups around the world that is constitutively active, can be transferred to envision the targeting of cancer cell EV secretion as a neighbouring cells and be functional. To understand viable strategy to reduce tumour burden and metastasis. if mutated β-catenin can be secreted via EVs, an The results from this study suggest that circulating EVs integrative proteogenomic analysis was performed can be rapidly taken up by the target cells in the tumour using exome sequencing data of LIM1215 human CRC microenvironment and allows for the amplification of the cells and proteomics data of EVs isolated. The analysis signal in favor of tumour progression. confirmed the presence of high amounts of mutant Lahiru Gangoda and Suresh Mathivanan β-catenin in EVs. Follow-up analysis confirmed that EVs La Trobe Institute for Molecular Science carrying mutant β-catenin altered the Wnt signalling La Trobe University activity in RKO CRC cells that bear wild-type β-catenin, both in vitro and in vivo. SILAC-based quantitative proteomics analysis confirmed the intercellular transfer of mutant β-catenin via EVs to the nucleus of the RKO cells. In addition to Wnt signaling activity, incubation of EVs with the recipient cells increased the migration of RKO cells. Intravenous administration of β-catenin containing EVs activated the Wnt signalling pathway and increased the tumour burden of mice implanted with RKO cells. Although the increase in migration of RKO cells or the tumour burden upon treating with EVs should be formally attributed to the entire EV cargo and not to mutant β-catenin alone, this study emphasises that EVs could switch the phenotype of the neighbouring and distant cells in favour of cancer progression. It is well known that tumours are comprised of different subpopulations of cancer cells that exhibit salient Mathivanan group from La Trobe University.
PAGE 14 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 SIMPLE, RAPID & EFFICIENT TISSUE CLEARING
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The ASBMB Education Feature is coordinated by Nirma Samarawickrema ([email protected]) and Tracey Kuit ([email protected]). Improving Learning Outcomes from Undergraduate Research Experiences Susan Howitt, Research School of Biology, Australian National University
Undergraduate research experiences (UREs) are Students need to feel that it is OK to admit to ignorance generally agreed to be a good idea as they provide and ask ‘silly’ questions. We saw many occasions students with an introduction to authentic research. where misunderstandings between students and While they are usually a positive experience, the learning supervisors arose because everyone assumed they outcomes students achieve are more problematic. We knew what they were doing. investigated this with an OLT-funded project nearly ten years ago. Since then, we have analysed data from more 3. Design the project carefully. A good project is one than 300 students to understand what students actually with a clear and achievable goal within the limited learn and how they perceive their supervision. time available in most UREs. Although much research One thing we noticed was a mismatch between today is done by multidisciplinary teams, your student learning outcomes expected by supervisors and should have some goals for their own small part. what students reported they learnt. Fig. 1 shows a Students who just slotted into someone else’s project hierarchical description of potential learning outcomes; generally reported a poor experience. Students value most supervisors want their students to obtain the full feeling ownership of their project and that they are range. However, students’ reported learning gains are trusted to make a contribution to your research, so generally confined to the less complex outcomes in make their role clear. the lower two tiers. To address this mismatch, we have suggested three tips for good URE supervision. More extensive analysis is published elsewhere (1–3).
1. Focus on learning, rather than research outcomes. Research is all about successful outcomes and we (often unconsciously) convey this to our students. In addition, when UREs are assessed through a lab report, which also emphasises results, students may equate getting results with a good project. However, we observed that the more complex learning outcomes were often evident when projects didn’t go well, as students then became more engaged with the process of research. Troubleshooting is an essential part of research but students might not understand this and sometimes interpret failure to get results as a personal failing. The supervisor has a critical role in normalising failure by discussing their own experiences and the importance of problem-solving skills. Students value a supportive supervisor who Fig 1. Potential learning outcomes from undergraduate helps them develop alternative approaches without research experiences. putting them under pressure to achieve positive results. These three things might seem obvious but we know from our extensive student data that they are often 2. Test your assumptions about what a student overlooked. Supervision is the single most important knows. Students may not have the background factor in determining the student experience (1,4). You knowledge to understand the scope or detail of your can support more complex learning by your student by research project. Ask them about what relevant helping them reflect on the scientific thinking behind the courses they have taken and listen to their answers. project as well as its day to day operation.
PAGE 16 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 ASBMB Education Feature
References 1. Howitt SM, Wilson AN, Wilson KF, Roberts P (2010) High Educ Res Dev 29(4):405–420. 2. Wilson A, Howitt S, Higgins D (2016) Assess Eval High Educ 41:901–916. 3. Wilson A, Howitt S, Higgins D (2016) Assess Eval Professor Susan Howitt High Educ 41:885–901. is Head of the Biology 4. Russell SH, Hancock MP, McCullough J (2007) Teaching and Learning Centre, Science 316(5824):548–549. Australian National University. [email protected]
Teaching Students to Work Effectively in a Group Nirmani Wijenayake, School of Biotechnology and Biomolecular Sciences, UNSW Sydney
The potential learning benefits of group work are towards group work? How do you demonstrate trust manifold. However, students are seldom taught how and openness towards others in your group? to work effectively in a group. Consequently, some • Establishing group-based assessments through students dislike group work and consider it stressful. The a quiz, which the students completed individually practical component of a second year Fundamentals and later finalised as a group. Working through the of Biochemistry course at UNSW is assessed in part quiz as a group enabled consolidation of knowledge through a group project. The task involves designing through peer-teaching/learning. an experimental protocol and applying it to identify a • Teaching students to benchmark their work by peer- metabolic disorder discussed in class. To encourage assessing draft reports, such that students develop students to work effectively in groups, we undertook the a dialogue between their work, others’ work and following: standards. This enabled students to recognise • Randomly allocating students into groups of four that there are multiple approaches to diagnose a to promote diversity (course of study, cultural metabolic disease and helped them learn from each background, prior experience). other. • Supporting students to connect by providing • Supporting students to communicate their findings icebreaker exercises. For example, to explore each through group oral presentations. other’s comfort with public speaking, students asked one another: Would you rather give or write the presidential speech? • Challenging students with a fun, low stake task to strengthen connections (e.g. build the tallest structure possible to support a marshmallow using 40 spaghetti sticks, scissors and cello tape – Fig. 1). Students had to brainstorm together to address this challenge. • Providing opportunities for conflict resolution within groups. Students were provided scenarios involving group work, which they had to appraise as a group to identify the issue, discuss strategies of resolution and develop a set of ground rules which they agreed to abide by. • Encouraging reflection by maintaining a weekly diary about their group experiences and thoughts about group work, which was monitored by staff. These Fig. 1. Building a structure to support a marshmallow. reflections enabled staff to better understand issues experienced, and identify strategies of support and Overall, students did extremely well in the assessment, interventions needed. As this task was assessed, with a mean score of 88%. Using a Likert scale survey, students were provided with prompts to facilitate we explored student perspectives of group work. The reflection, for example: What is your general attitude majority (88%) of students agreed or strongly agreed
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 17 ASBMB Education Feature that through the group activity they learned invaluable skills (Fig. 2) such as: • Strategies to meet deadlines • Problem solving through open discussions • Understanding some aspects of scientific research • Having the flexibility to be creative • Improving presentation skills • Seeing the real-life applications of biochemistry • Sharing the workload Student perception of group work • Using feedback to improve their work Fig. 2. (5 = strongly agree, 1 = strongly disagree). • Learning through teaching
Many students commented that the assessment task helped them to ‘make new friends’, ‘trust and rely on each other’ and ‘work effectively as a group’. As the Dr Nirmani Wijenayake is an semester progressed, students built a good rapport Education-focused Lecturer with members of their groups. Staff felt that this was and the Acting Deputy Director reflected by better engagement with group work. of Teaching in the School of Biotechnology and Biomolecular Sciences, UNSW Sydney. [email protected]
Harnessing Interdisciplinary Education in Biochemistry and Molecular Biology – an IUBMB Education Conference Janet Macaulay, Monash Biomedicine Discovery Institute, Monash University
The Education conference, Harnessing Interdisciplinary broad international representation (attendees came from Education in Biochemistry and Molecular Biology, was 22 countries) gave insights into the varied challenges run by the International Union of Biochemists and facing educators around the world. There were over 400 Molecular Biologists (IUBMB) and the Philippine Society attendees at the conference, including 20 winners of for Biochemistry and Molecular Biology (PSBMB) on IUBMB Tang Travel Bursaries. 13–15 November 2019 in Manila, the Philippines. The conference included keynote and plenary presentations and parallel sessions. The parallel sessions consisted of short talks followed by round table discussions to give attendees the opportunity to have in depth discussions with the presenters and other attendees. Jessica Gibbons, Monash University, won the Best Education Poster Award. Biochemistry and molecular biology are studied by students in programs ranging from science to health sciences, medicine and agriculture. As many of us know, when teaching in these varied programs, we can face a range of challenges as well as those issues specific to teaching students at various levels from K–12 through to postgraduate. Hence the conference was themed around program disciplines and levels and Fig. 1. Conference co-chairs Gracia Fe Yu (left; Chair also included continuing education in industry. Talks and of FAOBMB Education Committee, University of the discussions covered many interesting topics and the Philippines) and Janet Macaulay.
PAGE 18 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 ASBMB Education Feature
Researching and sharing our knowledge and understanding of education should be a core component of what we do as educators. The IUBMB journal, Biochemistry and Molecular Biology Education (BAMBEd), which aims ‘to enhance teacher preparation and student learning in Biochemistry, Molecular Biology and related sciences’ such as Biophysics and Cell Biology, facilitates the worldwide dissemination of educational material and scholarship. Hence, one of the conference parallel sessions was ‘Publishing in Education’ and included Phillip Ortiz, Editor in Fig. 2. Panel discussion speakers, from left: Philip Poronnik Chief of BAMBEd. All conference speakers were (University of Sydney), Xiaoyun Lu (Xi’an Jiaotong invited to contribute to a BAMBEd special issue, University, China), Anat Yarden (Weizmann Institute of based on conference presentations, which will be Science, Israel) and Joseph Provost (University of San published in 2020. Diego, USA). As well as gaining much from our wonderful discussions on education, we enjoyed the beautiful historic Manila Hotel conference venue and the excellent organisation and hospitality of our Filipino hosts. The conference dinner included wonderful BEAD RUPTOR ELITE food and a fascinating display of traditional culture and dance. Bead Mill Homogenizer The IUBMB is committed to supporting education Lyse up to 96 samples and training in a number of ways, including through in under 30 seconds an ongoing program of collaborative biannual education conferences in varied geographical regions. This was the second conference; the first was held in 2017 at the Weizmann Institute of Science, Israel. Plans are in progress for the 2021 conference, which will be run in conjunction with the American ASBMB. The proposed topic is ‘Big Data Science to Unify Teaching and Research’. Details of other opportunities are available on the IUBMB website and include funding for educational activities and education and research fellowships. You can also join the Friends of IUBMB to hear what’s going on. IDEAL FOR DNA/RNA Extraction, Cell and Tissue Lysis, Protein Extraction, Plant and Forensic Sample Disruption in volumes from 50 µL to 50 mL
Professor Janet Macaulay is Chair of the Committee for Education and Training, 02 9575 7512 IUBMB, and Associate www.capellascience.com.au Editor of Biochemistry and www.omni-inc.com Molecular Biology Education. [email protected]
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 19 ASBMB Education Feature
So, How Did I Do? Using Student Self-assessment to Steer Feedback Klaudia Budzyn, Department of Pharmacology, Monash University
It is well recognised that effective feedback is crucial those that they found challenging. Teaching Associates for motivating students to improve their work. Students (TAs) marked each student’s practical report on content, need to participate actively in this process, alongside assessed student performance relative to the learning their educators, in order to maximise the relevance outcomes and focussed on areas of difficulty identified of feedback to the students themselves. However, by the students. Thus, students received feedback on to achieve this, students first need to be able to their report and on the accuracy of their self-assessment. accurately assess the quality of their own work, identify In response to an end-of-semester survey, the majority and articulate areas they find challenging. This would of students indicated that they completed the check facilitate a shift from the more passive model of feedback sheet honestly and accurately. Approximately half of the as information transfer from educator to student, to students indicated that their self-assessment matched one that creates a dialogue between educator and that of their TA to some extent, with a similar proportion student (Fig. 1). We sought to determine whether finding subsequent feedback for their report useful. The providing students with a structured self-assessment most frequently chosen reason for finding this feedback template prior to submission of reports influenced their useful was that students could first nominate what they confidence in assessing their own work and modulated found challenging. This suggests that students are their perceptions of subsequent feedback. willing to reflect on their work, if given the opportunity. It is also possible that for students whose self- assessment did not match those of their TA’s, this could negatively influence how they responded to feedback. Although students need guidance in calibrating their ability to self-assess accurately, this skill needs to be developed in a supportive and sensitive manner. Students should also be given opportunities to demonstrate learning from feedback provided in future tasks. Despite this exposure to a structured form of self- assessment, nearly half the student cohort indicated that they still lacked confidence in doing this. It is therefore unsurprising that they were equally divided as to whether they were likely to change the way they approached self- assessment in the future. We have trialled this initiative with two separate student cohorts (Pharmacology and Biochemistry) at similar points in their degrees. Both cohorts share an overall lack of confidence assessing the standard of their work. This highlights the need to embed more opportunities Fig. 1. The current model of feedback (top) relies on one- for students to practice self-assessment early in their way transmission of information. However, the model university life, in order to gain confidence and recognise where students have input into feedback sets up a cycle of its importance. Only then can we realistically expect student reflection and evaluation that will inform feedback students to gain the most from feedback that will be (bottom), which can then be used by students to further valuable and relevant to them. reflect, evaluate and develop strategies for improving future tasks. Ultimately, this closes the feedback loop. We devised a check sheet for students to complete prior Dr Klaudia Budzyn is an to submitting their laboratory reports. Each check sheet Education-focussed Lecturer was incorporated into the laboratory report template in the Department and included key learning outcomes that students were of Pharmacology, expected to have achieved upon completing the class Monash University. activity. We queried students on their performance [email protected] against each learning outcome, aspects they did well and
PAGE 20 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 SDS Page: Short Discussions for Students Page
From Undergrad to Postgrad: How to Survive the First Year of your PhD Jessica Wyllie, La Trobe Institute for Molecular Science
The start of your PhD can be an exciting yet daunting you would earn at a full-time job. However, there are experience. Throughout your Bachelors study, and numerous grants out there designed to ‘top-up’ your perhaps even a Masters program, your studies and current scholarship or cover travel costs associated research are closely guided by academics, including with attending conferences. Even if you don’t think you your supervisor. Therefore, the transition to undertaking stand a chance, apply for the grants because if you PhD work can come as a shock to many, perhaps even don’t try, you will never know. Not only will these grants leading you to ask: Did I make the right decision to do help you financially, but receiving funding during your my PhD?; Can I really handle the pressure of a PhD?; PhD studies will look good on your CV when it comes Will three years be enough time to finish my project? time to apply for postdoctoral positions. It is easy to forget you’re not alone in this experience and that it is impossible to predict everything from day 4. Read, read, read one. However, there are ways to make the most of the I won’t be the first person to tell you to read widely and transition into your PhD program and to navigate the deeply, and I definitely won’t be the last. Reading papers pitfalls commonly encountered in your first year. and keeping up with the current literature in your field will be one of the most beneficial things you can do throughout 1. Look after yourself your PhD program. While you are still figuring out your A PhD program is hard, and I have yet to meet anyone project, spend some time catching up on the literature in that would say otherwise. The stress and self-imposed your field. It will assist you with your research planning long hours can take a massive toll on your health, and and experimental design, at the same time opening your not just physically. The prevalent self-doubt and anxiety mind to new ideas and technologies that can make your will be mentally draining. The frequent failures in the project stand out. And once your project eventually gets laboratory will make you question your decision to ever started, keep reading because new papers are published start a PhD in the first place. So, from day one, make sure all of the time and you never know what you’ll learn. to find a healthy work–life balance and don’t succumb to the common mistake of letting your PhD work consume 5. Last but not least, enjoy your PhD! your life. Whether it be spending time with friends and Your PhD program is going to be a huge part of your life family, going to the gym or even picking up a hobby at for the next few years. It will be tough and there will be home, finding a way to switch off when you leave the lab times when you wish you had chosen a ‘normal’ career, for the day will help you find this balance. But, if you do but don’t forget that your PhD will be a life-changing start to feel crushed by the pressure, no one will judge experience. By the end of the three or so years of you for taking a break and looking after yourself. You research, writing, giving talks and attending conferences, have three years ahead of you, so you don’t need to do the highs will far outweigh the lows. These activities also all your experiments in one month. provide essential skills development along your doctoral journey. So, celebrate the successes and learn from the 2.Don’t be afraid of your supervisor, they won’t bite failed experiments. Most importantly, have fun and enjoy Although we often forget, each of our supervisors has the moment whenever you can. been in our shoes before. They will have completed their own PhDs well before us and they all understand how the start of a PhD program can be overwhelming. Don’t be afraid to communicate with your supervisor about the struggles you are facing, both in and out of the lab. They are there to help guide you through your PhD studies, so the more open and honest you are with your supervisor, the more they can help you succeed. Jessica Wyllie is a PhD 3. Apply for grants, no matter how small candidate at the La Trobe Whilst the Australian PhD stipend is more generous Institute for Molecular Science. than in most countries, it is still a far cry from the money [email protected]
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 21 Competition:COMPETITION: Word Word Search Search Presenting the latest competition for the members of ASBMB. All correct Presenting theentries latest received competition by thefor theEditor members ([email protected]) of the ASBMB. All correct before entries May 2020received by the Editors ([email protected])will enter the draw to beforereceive XXXXXX a gift voucher. will enter With the thanksdraw to toreceive Joe Kaczmarski. a gift voucher. With thanks to Joe Kaczmarski. Complete the word search below. The unused letters along the shaded diagonal can be Completeunscrambled the word search to spellbelow. the The name unused of aletters common along type the shadedof molecule. diagonal can be unscrambled to spell the name of a common type of molecule.
ASBMB ASBMBBIOCHEMISTRY BIOCHEMISTRY CATALYSIS CATALYSIS CELL CRISPR CELL DNA CRISPR ENZYME DNA EVOLUTION ENZYME EVOLUTION GENE GENE GLUTATHIONEGLUTATHIONE GLYCOPEPTIDE GLYCOPEPTIDE KISTAMICIN KISTAMICIN LIPID LIPID METABOLISM METABOLISMNMR NMR PCR PCR PHAGE PROTEASOME PHAGE RESEARCHPROTEASOME RIBOSWITCH RESEARCH SYNBIO RIBOSWITCH SYNBIO VESICLEVESICLE VIRUS VIRUS
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PAGE 22 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 UNSCRAMBLED ANSWER: ______ASBMB Medallist and Awardee Profiles
The ASBMB Award recipients were to receive their awards, and the Lemberg Medal, Shimadzu Research Medal, SDR Scientific Education Award, Eppendorf Edman ECR Award and Boomerang Award recipients would have delivered their presentations at ComBio2020, which has now been cancelled due to the COVID-19 pandemic. Arrangements for the presentation of awards and delivery of the relevant lectures will be announced in due course. Many of the awards contain a travel component and each awardee had specified a conference or other training activity to which their award was to be applied. Since international travel and conference activities have largely been suspended, alternative arrangements will be made for these recipients to utilise their awards at a later date. The Lemberg Medal is awarded to a distinguished Australian biochemist or molecular biologist who will present the Lemberg Lecture at the annual ASBMB conference. The Medal is presented in memory of Emeritus Professor MR Lemberg, who was the Society’s first President and Honorary Member. Nominees must have been members of the Society for at least five years before the year in which the Medal nomination is to be considered. An honorarium is provided by ASBMB.
The Lemberg Medal Trevor Lithgow
Professor Trevor Lithgow graduated with a PhD in Biochemistry from La Trobe University in 1992. In 1993, he was awarded a Long-Term Fellowship from the Human Frontiers Science Program and moved to a postdoctoral position with Professor Gottfried (Jeff) Schatz at the University of Basel. In an unforgettable time in Switzerland; he worked to identify the components of the TOM complex, the key factor required in mitochondria for protein import and thereby organelle biogenesis. Ten papers were published on the discovery of the protein import receptors Tom20/Mas19 and Tom22/Mas22, including a paper in Nature reconstituting the initial steps of protein import and a review in Trends in Biochemical Sciences that set the model for how receptor cooperativity delivers protein substrates to the TOM complex, a fascinating molecular machine. In 1999, Lithgow was awarded the HFSP Tenth Anniversary Award that recognised the top ten Research Fellows in the first ten years of the Human Frontiers Science Program. A capstone to these discoveries came with recent work on the high-resolution structural analysis of the TOM complex published in three papers in Science, Molecular Cell and Nature. In 1996, Lithgow was recruited to La Trobe University to start his own laboratory, and in 1999 the lab moved to the Department of Biochemistry and Molecular Biology, University of Melbourne. In teaching, he developed three new subjects in Molecular Biology: a third year Molecular Aspects of Cell Biology unit, a multidisciplinary second year subject Integrated Biomedical Sciences I, and the Department’s first molecular cloning practical subject that used PCR, cDNA library screening and bioinformatic analysis to train approximately 150 students per year in these core techniques and the concepts for which they provide evidence. In 2008, Lithgow was awarded an ARC Federation Fellowship to build capacity for studying host–pathogen interactions at Monash University. In 2014, he took up an ARC Laureate Fellowship to develop nanoscale imaging approaches to investigate bacterial cell biology. This included developing applications of single particle cryoEM, neutron reflectrometry, atomic force microscopy and super-resolution imaging of bacterial cells. The fundamental discoveries from this work include how bacterial outer membranes are assembled and the intracellular complexity of the bacterial cytoplasm and periplasm. Lithgow also led the NHMRC Program in Cellular Microbiology that used the fundamental knowledge of bacterial cell biology to better understand mechanisms of antibiotic resistance, the mechanics driving entry of bacteriophage into bacteria and the mechanisms by which phages control host cell biology. In 2010, he was elected as a Fellow of the Australian Academy of Science. In 2020, Professor Lithgow was appointed as Director of the Centre to Impact AMR, in order to find sustainable solutions to the growing and global problem of antimicrobial resistance.
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 23 ASBMB Medallist and Awardee Profiles
The Shimadzu Research Medal is awarded to an outstanding Australian biochemist or molecular biologist with less than 15 years postdoctoral experience. The successful candidate will present the Shimadzu Medal Lecture at the ASBMB annual conference. Nominees must have been members of the Society for at least two years before the year in which the Medal nomination is to be considered. An honorarium is provided through the courtesy of Shimadzu.
The Shimadzu Research Medal Colin Jackson
Professor Colin Jackson heads the Chemical and Structural Biology Laboratory at the Research School of Chemistry (RSC), Australian National University. He is also the Associate Director of Research of the RSC. Colin’s graduate studies with Professor David Ollis defined the mechanistic basis for phosphate ester hydrolysis in a number of enzymes and was the beginning of an interest in the link between protein structural dynamics and function (Proceedings of the National Academy of Sciences USA, 2009). His PhD was awarded in 2007. He subsequently accepted a team leader position at the CSIRO after a short postdoctoral fellowship, where he worked with Dr John Oakeshott on the evolution of enzymes involved in insecticide resistance (Proceedings of the National Academy of Sciences USA, 2013). After being awarded a Marie Curie Fellowship, Colin then trained with Professor Martin Weik, an expert in kinetic crystallography, at the Institut de Biologie Structurale in Grenoble, France, and Professor Dan Tawfik, a pioneer in the field of protein evolution, at the Weizmann Institute of Science in Israel. Colin returned to Australia and was appointed an RSC lab head in 2011. Colin’s laboratory investigates the molecular and dynamic basis for protein function, protein evolution and protein engineering. Research highlights include: (1) mapping the changes in protein conformational landscapes during the evolution of new function (Nature Chemical Biology, 2016); (2) the engineering of a novel glycine sensor to follow neurotransmitter release in real-time (Nature Chemical Biology, 2018); (3) using ancestral protein reconstruction to recapitulate the emergence of enzymatic activity from a non- catalytic scaffold (Nature Chemical Biology, 2018); (4) revealing that the suboptimal activity of a designed enzyme originates from frequent sampling of non-catalytic states (Nature Communications, 2018); and (5) overcoming insecticide resistance through the development of a new class of inhibitors (Proceedings of the National Academy of Sciences USA, 2019). These compounds are currently under a commercialisation agreement. Colin has published over 100 articles in top journals such as Nature Chemical Biology, Nature Immunology, Nature Communications, eLife and Proceedings of the National Academy of Sciences USA. He is the recipient of a 2011 Discovery Early Career Researcher Award, 2012 HFSP Young Investigator Award, 2014 ARC Future Fellowship, 2014 Tall Poppy and Act Tall Poppy of the Year, 2015 ACT Scientist of the Year and 2015 RACI Rennie Memorial Medal.
PAGE 24 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 ASBMB Medallist and Awardee Profiles
The SDR Scientific Education Award rewards outstanding achievement in education in biochemistry or molecular biology, especially innovation and creativity in education, with a view to fostering leadership in this important area of the Society’s objectives. The Award will enable the recipient to participate in an international conference with a significant focus on education, or to spend a period of time at another institution (in Australia or overseas) for the purposes of undertaking developments in education in biochemistry and molecular biology. The recipient will present a lecture within the Education Symposium at the ASBMB annual conference. Applicants must have been members of the Society for at least two years before the year in which the Award application is to be considered. The contribution to travel expenses is provided through the courtesy of SDR Scientific.
SDR Scientific Education Award Nirma Samarawickrema
The educator I am today is because of my students. I love my teaching and enjoy my research and each enriches the other, adding value to both. Involving my students and peers, and integrating learning into this mix is what fires me as an educator! My learning followed a traditional path of completing my BSc and MSc at the Australian National University and PhD in Molecular Parasitology/Biochemistry at the University of Queensland. I began my teaching career as a demonstrator at Kelaniya University, Sri Lanka. My students were school leavers from diverse socioeconomic backgrounds, many undertaking urban relocation and experiencing study in English (a second language) for the first time. As a new academic, my approach was to convey content knowledge and dictate the learning process. However, I soon learnt that my students found Biochemistry ‘difficult’ and irrelevant to their medical careers. This feedback meant I had to find ways of actively engaging students and embedding career-connections in their learning so that they were scaffolded to succeed and become empowered to persist beyond first year. As a senior lecturer at Monash University, Australia, I continue to teach first year subjects. I coordinate units and teach Biochemistry to multiple student cohorts (medical, biomedical, nutrition and science) across the medical and science faculties. My classes are large (>700), where students come from diverse backgrounds, capabilities, expectations, with many transitioning to university from other types of work. Mindful of this diversity in my classes, I have focused my teaching to facilitate lifelong learning in students through partnerships. My first-year students are lively, eager to learn and keen to enjoy university life. I have discovered that their voice is a rich resource in the classroom – they each have a unique perspective to offer. This learning has transformed my teaching as I have increasingly grown to consider my students as my partners in teaching and learning. In the last ten years as I transitioned to be an education-focused academic, I broadened my research focus to include the scholarship of teaching and learning (SoTL), while retaining some aspect of my disciplinary research. I have drawn on my disciplinary research on human papillomavirus and cervical cancer to develop learning activities now integrated into the curricula and utilised it to initiate my research interests in teaching and learning. My SoTL research focus is broadly on partnerships (students, teaching associates and academics) and on building assessment literacy that enhance teaching and learning. In recognition of demonstrating sustained leadership and innovation in education, I was elected a Fellow of the Monash Education Academy and Fellow of the Higher Education Research and Development Society of Australasia. I love teaching Biochemistry to young students. As rewarding as it is, I feel deeply accountable as I foster the biochemists of future generations.
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 25 ASBMB Medallist and Awardee Profiles
The Eppendorf Edman ECR Award is awarded to an ASBMB member with no more than seven years postdoctoral experience (or equivalent taking any career disruption into account), in recognition of their outstanding research work. The Award provides funds to assist the recipient to attend an overseas conference in a field associated with biochemistry or molecular biology or to visit briefly a research laboratory in Australia or elsewhere to access specialised equipment or to learn new research techniques. The recipient will present a lecture within a symposium at the ASBMB annual conference. Applicants must have been members of the Society for at least two years before the year in which the application is to be considered, or must have taken out a three year membership in the year of the application. The contribution to travel expenses is provided through the courtesy of Eppendorf South Pacific.
Eppendorf Edman ECR Award Si Ming Man
Si Ming completed a Bachelor of Medical Science (Hons I, University Medal) at UNSW Sydney. During his Honours year, Si Ming investigated the role of mucus-associated bacteria in children with inflammatory bowel diseases. His interests in host–pathogen interaction inspired his move to the UK, where he completed his PhD at the University of Cambridge in 2013 under the supervision of Professor Clare Bryant. During his PhD, he studied macrophage responses to the foodborne pathogen Salmonella spp. and generated two first-author publications in Proceedings of the National Academy of Sciences USA and a first-author publication in the Journal of Immunology. With the support of an NHMRC RG Menzies Early Career Fellowship, Si Ming moved to Memphis, Tennessee, USA, where he completed his postdoctoral training at St Jude Children’s Research Hospital under the mentorship of Dr Thirumala- Devi Kanneganti. During this time, Si Ming and his colleagues identified (1) a role for disease-fighting proteins in liberating microbial ligands to drive activation of innate immunity (Cell, 2016; Nature Immunology, 2015); (2) the activation mechanisms of immune receptors in cancer (Cell, 2015; Nature, 2016). Si Ming returned to Australia to establish his lab at the Australian National University in 2017. He is now a Professor and NHMRC RD Wright Biomedical Fellow. His laboratory focuses on understanding the role of innate immunity in the host defense against infectious diseases and the development of cancer (Nature Microbiology 2019, Nature Communications, 2020). Si Ming was a recipient of the Pfizer-Showell Award (2019) and the Thermo Fisher Trainee Achievement Award (2016) from the American Association of Immunologists, the Milstein Young Investigator Award from the International Cytokine and Interferon Society (2016), the Jim Pittard Early Career Award from the Australian Society for Microbiology (2017), the Royal Society of NSW Edgeworth David Medal (2019), an NHMRC Research Excellence Award for the highest-ranked Early Career Fellowship (2015) and an NHMRC Research Excellence Award for the highest-ranked Career Development Fellowship Biomedical Level 1 (2019). He also received the 2019 Commonwealth Health Minister’s Medal for Excellence in Health and Medical Research.
PAGE 26 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 ASBMB Medallist and Awardee Profiles
The Boomerang Award is offered to an outstanding expatriate Australian biochemist or molecular biologist to provide an opportunity to return to Australia to present their work in a Symposium at the annual ASBMB conference and to give seminars at universities or research institutes in at least one other Australian city. The Award is intended to provide the awardee with exposure in Australia and to facilitate interactions with local researchers. Applicants must have been a member of a recognised Australian scientific society for at least two years, or must have taken out a three year membership in the year of the application, and awarded their PhD not more than ten years prior to the closing date (or equivalent taking any career disruption into account). The contribution to travel expenses is provided by ASBMB.
Boomerang Award Matthew Doyle
After completing his BSc (Biotechnology) in 2011 at the University of Adelaide, Dr Matt Doyle was fast-tracked into postgraduate research through the award of a ‘No Honours’ scholarship. Working with Associate Professor Renato Morona at the Research Centre for Infectious Diseases, Matt developed methods to investigate how outer membrane proteins (OMPs) of Gram-negative bacteria are transported to, and/or translocated across, the bacterial cell surface. For this work he used a model OMP called IcsA, which is an essential virulence factor for Shigella species to cause bleeding diarrhoea in humans. He identified motifs within IcsA that drive correct membrane localisation andare conserved in thousands of OMPs across many Gram-negative pathogens. Matt’s PhD studies contributed towards six research articles and attracted multiple awards including the 2014 Adelaide Protein Group Speaker Award and the University Doctoral Research Medal. After completing his PhD in 2015, Matt was awarded a National Institutes of Health (NIH) Visiting Fellowship to conduct postdoctoral training in the laboratory of Dr Harris Bernstein in the USA. At the NIH, Matt has designed the first experimental system that can controllably trap new OMPs in the final stages of membrane integration and folding in cells. By combining in vivo protein–protein disulphide crosslinking approaches, he mapped the interactions of a new OMP with the folding machinery known as the BAM complex. BAM contains protein subunits conserved in all Gram-negative bacteria as well as organelles such as mitochondria and chloroplasts. This work resulted in a new model for OMP membrane integration and was published in 2019 in Nature Communications. Apart from his research at the NIH, Matt has also been recognised for his mentoring through a 2018 NIH Research Mentor Award, which provided mentoring training as well as salary for a summer intern from a socioeconomically disadvantaged background. Matt remains captivated by the study of OMP biogenesis and argues that the information is critical for the design of new antibiotics, a better understanding of how bacteria cause disease and the improvement of bioprocessing technologies. He attributes his past successes to a multidisciplinary approach to experiment design (e.g. biochemistry, structural biology, and microbiology). Matt wishes to eventually return to Australia to continue his research and pursue an academic career. Matt thanks the ASBMB for this amazing opportunity to share new findings at an ASBMB meeting and to visit laboratories in Australian cities including Canberra (Dr Denisse Leyton, Australian National University) and Melbourne (Professor Trevor Lithgow, Monash University).
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 27 ASBMB Fellowship Profiles
The ASBMB Fellowships are awarded annually to biochemists or molecular biologists, in their early career and normally resident in Australia, in recognition of their outstanding work in an area of biochemistry and molecular biology. The Fellowships provide funds to assist the recipient to attend an overseas conference in a field associated with biochemistry or molecular biology or to briefly visit a research laboratory in Australia or elsewhere to access specialised equipment or to learn new research techniques. Applicants must be at least in the second year of PhD training and not more than two years subsequent to the award of the PhD degree. Applicants must have been members of the Society for least one year immediately prior to application.
Amy Baxter – recipient of the Fred Collins award for the most outstanding ASBMB Fellowship applicant Dr Amy Baxter completed a Bachelor of Human Nutrition in 2009 at La Trobe University in Bundoora, Victoria. She continued on at La Trobe, completing her Honours year in 2010 and PhD from 2012–2017 (including maternity leave periods for each of her two children, now aged four and seven) in the Department of Biochemistry and Genetics under Professor Mark Hulett. During this time, Amy investigated the molecular basis of tumour cell membrane disruption by plant defensins, discovering that defensins can bind membrane phosphoinositides in target cells and form oligomeric structures to mediate cell lysis. Her research made a significant impact in the innate immunity field, reflected in the ten papers published during her PhD, including in eLife and Cell Death and Differentiation, generating over 300 citations. In 2018, Amy was awarded an NHMRC Peter Doherty Early Career Fellowship to examine the mechanism and functions of extracellular vesicles formation during cell death, which she is currently undertaking under the supervision of Associate Professor Ivan Poon at the La Trobe Institute for Molecular Science (LIMS). She is currently investigating the roles of apoptotic cell disassembly and clearance in the context of vascular inflammation. Amy’s achievements, both during her PhD and since, have been recognised through her nomination for several research awards including the La Trobe University Nancy Millis Medal for Outstanding Theses (2017), Victorian Premier’s Award for Health and Medical Research (2019 Finalist, Basic Science category) and La Trobe University ECR Research Excellence Award (2019). Amy was scheduled to present her recent findings at the Gordon Cell Death Conference in Ventura, California, in June 2020.
Steffi Cheung Dr Steffi Cheung completed her Bachelor in Science (Honours) at the University of Melbourne in 2014. She was awarded the MIRS and MIFRS scholarships by the University of Melbourne to undertake her PhD studies at the St Vincent’s Institute of Medical Research/Department of Biochemistry and Molecular Biology at the University of Melbourne under the mentorship of Professor Michael Parker in 2015. Her doctoral studies focussed on studying the signalling mechanism of the beta common family of cytokines, where she employed various biophysical techniques to complement her structural biology studies. She was awarded her doctoral degree in 2019, resulting in four publications. Her performance was also recognised by several awards, including the 2018 Sawyer Medal recognising her exceptional scientific contribution during her doctoral studies in the Department of Biochemistry and Molecular Biology at the University of Melbourne and the 2017 International Union of Crystallography Young Scientist Award, amongst others. She presents her work at local and international conferences, being invited to present her doctoral work at the CRYSTAL32/AsCA2018 conference and being awarded the 42nd International Lorne Protein Structure and Function Poster Prize. Steffi is now a postdoctoral researcher in the Structural Biology and Computational Design laboratory at the Bio21 Institute. The ASBMB Fellowship was to give Steffi the opportunity to attend the 25th Congress of the IUCr assembly, Prague, Czech Republic, to help diversify her structural biology skills.
PAGE 28 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 ASBMB Fellowship Profiles
Anukriti Mathur Anukriti is a third year PhD student at the Australian National University under the supervision of Professor Si Ming Man. Her PhD project focuses on understanding the molecular mechanism of bacterial toxins in inducing cell death and inflammation. Her research identified two multicomponent bacterial toxins assembled in a specific and linear order on the mammalian cell membrane to form a lytic pore, to activate the immune sensor. These findings have been published in Nature Microbiology and Nature Communications, with Anukriti as a first/co-first author. She has published two review articles inMicrobiology and Molecular Biology Reviews and Journal of Leukocyte Biology. Anukriti completed her Bachelor of Technology in Biotechnology at Amity University, India, in 2010. She received a Master of Engineering in Biotechnology from the Birla Institute of Technology & Science, Pilani Campus, India, in 2016. In 2015, she was awarded a Khorana fellowship by the Government of India which allowed her to conduct a research project at the Harvard Medical School, USA. Anukriti’s doctoral work has been recognised by a Gretel and Gordon Bootes Medical Research Foundation grant award, an American Association of Immunologists trainee poster award, an International Cytokine and Interferon Society Sidney & Joan Pestka Graduate Award, an Australian Society for Microbiology Nancy Millis student award and an International Association of Inflammation Societies Young Investigator Award. This ASBMB Fellowship was to give Anukriti an opportunity to present her research findings at the American Association of Immunologists annual meeting in Honolulu, USA, and meet potential employers and collaborators.
Mengjie Hu Dr Mengjie Hu completed her Bachelor of Science at the University of Melbourne, followed by a Masters degree in Biomedical Science in 2012, where she investigated mitochondrial biochemistry with Associate Professor Marie Bogoyevitch at the Bio21 Institute, leading to a first author publication in Biochemical Journal. Mengjie subsequently worked as a Research Scientist and Project Team Leader in a multinational pharmaceutical company. In 2014, she commenced her PhD at the University of Melbourne with the support of Melbourne International Research and International Fee Remission Scholarships in the labs of Associate Professor Marie Bogoyevitch and Professor David Jans (Monash University). There, she investigated how infection by respiratory syncytial virus (RSV) impacts mitochondrial morphology and function, and conversely how manipulation of mitochondrial function can impact RSV infection. Her work developed a new therapeutic approach to combating RSV infection, culminating in first author publications inBiochemical and Biophysical Research Communications, eLife, Cells, and a comprehensive review in Physiological Reviews, as well as several awards in 3 Minute Thesis Competitions. Mengjie was awarded her PhD in 2019 along with the Sawyer Medal from the Department of Biochemistry and Molecular Biology at the University of Melbourne in recognition of her outstanding research achievements. Since then, Mengjie has worked on a number of projects involving other infectious viruses including Dengue and Zika, and has recently embarked on a new journey in clinical research. This ASBMB Fellowship was to give Mengjie an opportunity to present her findings at the 16th World Congress on Virology, Emerging Diseases & Vaccines in Italy, and then visit several eminent laboratories at Imperial College in London.
Editor’s note: What a fitting conference and location in light of the current COVID-19 pandemic. There will certainly be lots of new data to discuss when this conference is rescheduled.
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 29 Science meets Parliament 2019
Matthew Johnson and Vanessa Vongsouthi report on SmP2019
‘You could be the best violinist in the world, but if you’re Wood gave an inspirational speech of her experience of in a soundproof room, it is a waste.’ Winthrop Professor translational research and how it can be used to improve Fiona Wood’s opening address resonated with a room the treatment of burns victims. Professor Wood’s story full of STEM experts from across the nation, kicking off exemplified how basic research can be translated Science meets Parliament 2019. The annual Science and into real health outcomes with determination and Technology event celebrated its 20th anniversary last perseverance. Australia’s Chief Scientist, Professor Alan year, gathering STEM professionals for a two-day event Finkel, and New Zealand’s former Chief Science Advisor, with the Australian Parliament. The event is designed to Professor Gary Evans, spoke about their experience educate STEM researchers about policy and governance, advocating for science and technology in Parliament. and connect researchers with parliamentarians to Professor Finkel talked specifically about the role that talk about science and its role in Australia’s health, Australia might play in the production of clean hydrogen environment, wealth and wellbeing. The ASBMB, an fuel for industry both in Australia and abroad, as opposed affiliate of Science Technology Australia, sponsored us to the fossil fuel exports that the Australian government (Vanessa Vongsouthi, ANU PhD candidate and ASBMB currently supports. Discussion was centred on the role of member, and Dr Matthew Johnson, ASBMB’s ACT State science in advising public policy, in the face of a growing Representative) to attend the event and communicate presence of an anti-science culture in Australian politics. our experience. Science meets Parliament offers two tracks, one geared for first time attendees, another for returning veterans. As this was our first time, we attended track one, which started with the ‘New to Canberra’ panel discussion featuring Paul Osborne (Bureau Chief and Journalist), Dr Sarah Pearson (Chief Scientist for Department of Foreign Affairs) and Sarah Cullens (Principle Consultant for Nexus Public Affairs). The session detailed how the media, lobby groups, public service, and advocacy groups influence government. Each panellist gave a detailed account of how their profession impacts government policy, and advice on how representatives from STEM can do the same. How a message is portrayed is as important as the message itself; scientists are often guilty of communicating with too much jargon, for too long and being too abstract. For members of Parliament, who primarily deal in votes, making your ideas real and relevant to them and their electorate is important to getting From left: Trent Zimmerman MP, Alexandra Thomson, your message across. Fortunately, we had ample help Kristine McGrath and Matthew Johnson. and time to prepare our pitches. In the session ‘Practicing As per previous Science meets Parliament events, your Pitch’, Dr Will Grant and Dr Rod Lamberts gave us day one was aimed to educate attendees about the the tools to ditch the jargon and simplify our science. inner workings of Parliament, and prepare everyone In one exercise, we iteratively distilled our pitch down for their meetings with parliamentarians using a range from several minutes to as little as ten seconds. It was of eminent speakers and workshops. Science meets amazing to see how creative people in STEM can be with Parliament is all about communicating and networking their pitches when time was restricted. The session was and while sitting at round tables with delegates from a fantastic experience for communication that geared us across STEM, we had to concisely introduce ourselves up for the networking events that followed. and say what we do, all within one minute. The diversity Our first chance to meet Senators and Parliamentarians of attendees was immediately apparent – museum was at the ANSTO sponsored Gala Dinner held in the curators, representatives from public policy think tanks, Great Hall. Our evening, hosted by SCOPE TV presenter, science commentators and biotech researchers, to Lee Constable, provided a great opportunity to practice name a few. For many researchers, who are accustomed our networking skills. Unfortunately, the parliamentarians to networking at subject specific conferences, this expected to sit at our particular tables were unable to environment was already a welcome step outside our attend. However, it was fascinating to meet people who comfort zones. In her opening address, Professor work in different STEM-related jobs, many of which we
PAGE 30 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Science meets Parliament 2019 didn’t realise existed. During dinner, we heard from The for North Sydney who supports same-sex marriage and Hon Karen Andrews MP (Minster for Industry, Science recently the full legalisation of e-cigarettes. Despite a and Technology) and The Hon Brendan O’Connor MP busy schedule, Mr Zimmerman met with myself and two (Shadow Minister for Employment and Industry, Science, other STEM representatives. Mr Zimmerman was very Small and Family Business) about their visions for STEM engaging and interested in our various areas of research, in Australia. and we had a short discussion regarding my research Day two of Science meets Parliament was largely about on resistance to antibiotics and the development of the personal meetings with an assigned parliamentarian. novel treatments. Unfortunately, the bells rang and We were assigned to meet Trent Zimmerman MP and parliamentary business cut our meeting short. Mr Perrett Graham Perrett MP (Shadow Assistant Minister for is a Labor MP for Moreton, teacher, lawyer and author. Education and Training). Mr Zimmerman is a Liberal MP He met with Vanessa and four other delegates, taking the time out of his day to have an exciting discussion about STEM teaching in Australia, graphene water-filtering technology, and Vanessa’s research on plastic-degrading enzymes. Science meets Parliament concluded with a panel discussion with Ministers from both sides of politics answering questions from the STEM community. The lack of science in policy making was a prominent topic. The blame was placed on the STEM community for not communicating to politicians and the wider community clearly enough. On the topic of climate change, we were reassured that climate change denial is not prevalent in Australian politics and that the discussion has moved on to what we need to do about it. However, considering this panel discussion and the recent push by parliamentarians for a science watchdog, it seems that communication between STEM, the public and Parliament is more important than ever. From left: Tim Rawling, Vanessa Vongsouthi, [email protected] Erika Duan, Leanne Cameron, Timothy [email protected] van der Laan and Graham Perrett MP.
Call for Expressions of Intent – AAS Boden Conference Award
The Australian Academy of Science established the Boden Conference Award to fund small specialist conferences in the biological sciences with the generous support of the late Dr Alex Boden AO FAA. These conferences, which usually run for about two days, bring together researchers working in rapidly advancing fields to discuss current advances and problems. A sum of up to $10,000 is provided, and organisers are encouraged to seek additional funding from other sources. One conference is funded annually. Applications close: 9:00am 1 June 2020 Further information: Boden Conferences page on AAS website Contact: [email protected] or (02) 6201 9407
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 31 Sydney Protein Group: an ASBMB Special Interest Group
(Macquarie University) presented her work on the pre- dominance of paucimannosylation in human cancers, and its potential use as a cancer biomarker. Yicheng Jessica Zhong (University of Sydney) detailed her single molecule work probing the mechanism by which CHD4 enables nucleosomes to slide during chromatin The Sydney Protein Group (SPG) is comprised of remodelling. The penultimate speaker, Yi Zeng (VCCRI), scientists and students from academia, hospitals and showcased his cryo-EM structures of archeal TF55 industry who are interested in all aspects of protein science chaperonin from Sulfolobus solfataricus, suggesting that research. Founded in the 1980s, the SPG promotes the protein may form filaments to regulate chaperone protein science, and supports students and early- and activity. Lastly, Ngee Kiat Jake Chua (UNSW) described mid-career researchers (EMCRs) in the field. With the his PhD project looking at the regulation of squalene help of funding from the ASBMB and trade partners, monooxygenase – an important player in cholesterol SPG organises a number of events throughout the year, homeostasis. with an emphasis on providing opportunities for students The symposium guest speakers, international NMR and EMCRs to present their research and enhance their spectroscopists Ad Bax, Rasmus Linser and Kevin network at high quality scientific conferences. Gardner, were judges for the event. Jessica Zhong was Over the past year, the SPG has organised a number announced as winner of the 2019 Thompson Prize. of local and national events. One of the initiatives of the Conference travel awards were also given to three ASBMB is to provide a SIG-sponsored presentation at students, in recognition of their research achievements ComBio/ASBMB conferences for a promising early- so far. The ATA Scientific, ANSTO and Greg Ralston career researcher. This year, James Walshe from the Memorial Prize travel awards were awarded to Charlotte Victor Chang Cardiac Research Institute was awarded Franck (University of Sydney), Serene El-Kamand the scholarship and presented his cryo-EM research (Western Sydney University) and Teegan Lawson into E. coli ATP synthase at ASBMB 2019 in Fremantle. (Western Sydney University), respectively, to attend the At this meeting, the SPG also hosted a SIG session to Lorne Proteins or Proteomics Meetings. showcase the research being conducted by protein scientists from across New South Wales, which was sponsored by the ASBMB. The session saw recent highlights from Chandrika Deshpande (Centenary Institute) on the role of calcium for metal efflux by ferroportin transporters; Karishma Patel (University of Sydney) on the structural diversity of high-affinity cyclic peptides that inhibit bromodomains; Bishnu Paudel (University of Wollongong) on the activity of human telomerase on G-quadruplexes at single-molecule resolution; and Emma Sierecki (UNSW) on the different Jessica Zhong interactions of the Mediator complex. (left) receives the One of the most anticipated nights on the SPG calendar 2019 Thompson Prize is the annual Thompson Prize, named in honour of the from SPG President, eminent local protein scientist, E.O.P. (Ted) Thompson. Liza Cubbedu. Students are encouraged to submit abstracts to secure a speaking spot, and the best oral presentation of the The SPG Annual General Meeting was held immediately night is awarded the prestigious Thompson Prize. The after the Thompson Prize ceremony and, after almost 28th Annual Thompson Prize was held in conjunction ten years of leading the SPG community, Liza Cubbedu with a half-day symposium on 22 November 2019 at the (President) and Roland Gamsjaeger (Committee University of Sydney, hosted by Joel Mackay and Jason Member/Webmaster) stepped down from the leadership Low. The evening showcased some of the high calibre team. We cannot thank Liza and Roland enough for their research being conducted by students from all around tireless work in supporting SPG members and promoting the greater Sydney area, and was well attended by the local protein science over the years. The quality of SPG community. speakers at the Thompson Prize event is a testament to Harry Rathbone (UNSW) described his work on their hard work and the reputation of the SPG initiative. phycobiliproteins and how the cryptophyte Hemiselmis Tara Christie (University of Sydney) and Alastair Stewart andersenii have adapted these proteins to capture (VCCRI) were then elected as President and Committee various wavelengths of light. Next, Sayantani Chatterjee Member/Webmaster, respectively. They are committed
PAGE 32 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Sydney Protein Group: an ASBMB Special Interest Group to growing a collaborative and productive network of AXT Pty Ltd for supporting this event, which enabled protein scientists. SPG to put together such an impressive and stimulating To kick off 2020, a mini-symposium was held in program for the local protein community. The SPG looks February at the University of Sydney. The afternoon forward to another great year of hosting protein science featured talks from distinguished researchers Antoine events and supporting the fantastic research being van Oijen (University of Wollongong), Marc Wilkins conducted by local protein scientists. (UNSW), Margie Sunde (University of Sydney) and Andrei Lupas (Max Planck Institute for Developmental Tara Christie (President) and Jason Low (Secretary) Biology, Germany). This event was well received by the Sydney Protein Group community, as evidenced by the large turnout and lively https://www.asbmb.org.au/ discussions following the talks. We thank ASBMB and special-interest-groups/sydney-protein-group/
Election of Council 2021
Nominations are called for the following positions on the Council of the Australian Society for Biochemistry and Molecular Biology Inc for 2021: Secretary, Treasurer, Editor, Secretary for Sustaining Members and State Representatives.
The ASBMB Council President J Mackay # Eligible for for the period President Elect J Matthews re-election 1 January 2020 to Secretary B Forbes § § Position open 31 December 2020 Treasurer M Kvansakul # is composed of the Editor T Soares da Costa # following members: Education Representative N Samarawickrema # Secretary for Sustaining Members S Jay #
Representatives for: ACT M Johnson § NSW K Quinlan § Vic E Lee § Qld B Schulz § SA M Pittman # Tas K Brettingham-Moore § WA M Murcha §
Nomination forms are available on the ASBMB website. Nominations for all vacant positions must be signed and seconded by members of the Society. The nominations must be signed by the nominee to indicate his/ her willingness to stand. If more than one nomination is received for any position, a ballot will be held at the Annual General Meeting. All members will be notified of any elections and members not attending the Annual General Meeting may submit a proxy form available from the Secretary.
NOMINATIONS MUST REACH THE SECRETARY BY AGM IN SEPTEMBER/OCTOBER 2020 (DETAILS TO BE ADVISED).
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 33 Biochemistry on Stage
Systematic Absences Terry Mulhern, Department of Biochemistry and Molecular Biology, University of Melbourne
In October 2019, deep underground in the bowels of the the result is complex and beautiful. Geometric patterns University of Melbourne’s Bio21 Institute, a dozen VIPs form composed of lines of spots of varying intensity are clustered around a scientific instrument resembling with occasional gaps – so called ‘systematic absences’. a large squat refrigerator. These aren’t overseas In days gone by, these images were captured on scientists, entrepreneurs or politicians. They are actors. photographic film. Photograph 51 was the understated This is the cast of the Melbourne Theatre Company’s name given in 1952 by the trailblazing female scientist production of Anna Ziegler’s play, Photograph 51. Rosalind Franklin, to the most famous X-ray diffraction image ever captured. In a dank basement at King’s College in post-second world war London, Rosalind Franklin used a much more rudimentary diffractometer to record photograph 51. Time and time again, she and PhD student Raymond Gosling painstakingly aligned semicrystalline fibres of DNA in the X-ray beam and recorded photographs. By controlling the humidity inside the diffractometer, Franklin was able to tease apart the contributions from the A and B forms of DNA. Photograph 51 was recorded under higher humidity, which favours the more hydrated and elongated B form that more closely resembles the state of DNA in living cells. Photograph 51 subsequently fell into the hands of a brash young American working at Cambridge University, Nadine Garner as Rosalind Franklin and James D Watson. It contained the key information that Gig Clarke as Ray Gosling. Photo: Pia Johnson. allowed Watson and his older English colleague Francis Crick to propose their famous double helix structure of Since 2010, Photograph 51 has been performed to DNA. Their model for DNA was elegant in its simplicity packed houses from New York to Stockholm. In 2015, and earth shattering in its significance. This great leap it played in London’s West End with Nicole Kidman forward paved the way for the genomics revolution in the leading role. Pamela Rabe is to direct its run that we are immersed in today. In recognition of this at the Fairfax Theatre in the Melbourne Arts Centre discovery, Watson, Crick and Franklin’s male colleague, (1 November–14 December 2019). The cast, including Maurice Wilkins, received the 1962 Nobel Prize for Nadine Garner (The Doctor Blake Mysteries), are here Medicine. But not Rosalind Franklin. She died of ovarian to school themselves in the dark arts of X-ray diffraction cancer in 1958. Ironically, Franklin’s premature death and to hear the perspectives of real scientists on the averted a controversy that was brewing. Watson and motivations, rivalries and sexual politics at the heart of Crick’s place in history was assured, but either Franklin the story they will portray. or Wilkins would have had to miss out. Nobel Prizes can The group listen intently, as crystallographer Megan be shared by no more than three individuals. Maher explains the operation of the X-ray diffractometer. The intellectual and emotional conflict of the fraught The bottom half, containing the X-ray generator, is relationships still fascinates us, more than 70 years completely enclosed by metal shielding, but a window in the top half reveals an assembly of gleaming metal devices. Several probe-like appendages converge to a single point. Here, a narrow powerful beam of X-rays is focussed onto a tiny crystal of biological material. The X-rays impinge on the crystal and are then scattered in all directions by the ordered crystalline lattice of molecules. The emergent waves of energy interfere with each other constructively and destructively. In some directions, they add together to become more Photograph intense but in other directions they annihilate each other 51. and vanish. When the diffracted beams hit the detector, PAGE 34 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Biochemistry on Stage
Karen Day, molecular biologist Heather Verkade and structural biologists Megan Maher and I momentarily pause and then, unanimously agree: ‘No’. What they did was wrong. And it is not a matter of different standards for different times. It was wrong then and it is still wrong now. In Cambridge, Max Perutz improperly gave a report on Franklin’s work to Lawrence Bragg, which then found its way into the hands of Watson and Crick. Although argument has ensued for decades, it is doubtful that Watson and Crick should ever have been allowed to see it. At King’s College, Wilkins then overstepped his authority by handing Watson photograph 51 without consulting Franklin. Imagine how you would feel if your grant application containing unpublish data was ‘shared’ Rosalind Franklin on vacation in Tuscany, spring 1950. with your competitors; and then to top it off, a senior Photo: US National Library of Medicine. colleague gifts them your raw data behind your back? on. The way Watson and Crick learned the details of Franklin’s experiments and how Watson obtained her diffraction pattern speak volumes about the attitudes towards women in science and society of the time. Back upstairs in the Bio21 boardroom, we show the cast 3D animations of DNA molecules and talk about the meaning of different geometric features of photograph 51. We explain how the X shape indicates helical structure and that the layer lines define repeating distances. The systematic absence of the fourth layer Acknowledgements section from line indicates that the two twisted DNA strands are Rosalind Franklin’s April 1953 Nature paper (3). offset by 3/8 of a turn. This asymmetry gives rise to the major groove and minor groove in the structure where The acknowledgements section of a thesis or paper (as we now know) protein machines can nuzzle into the can be fascinating and revealing. Like diffraction structure and read its blueprint. patterns, there is information in what is both present and We are bombarded with questions, both technical missing. Three papers, authored by Photograph 51’s key and about what it is like being a scientist. The most protagonists, appeared back-to-back in the April 1953 telling was, ‘Do you think what Watson and Crick did issue of Nature. Watson and Crick acknowledge having was right?’ The four scientists in the room, geneticist been ‘stimulated by a knowledge of the general nature of the unpublished experimental results and ideas’ of Wilkins and Franklin (1). In his paper, Wilkins thanks Watson and Crick for ‘stimulation’ and Franklin for ‘discussion’ (2). Tellingly, Rosalind Franklin is ‘grateful’ to just Wilkins and Crick (3). James D. Watson’s name is a systematic absence.
References 1. Watson JD, Crick FH (1953) Nature 171:737–738. 2. Wilkins MHF, Stokes AR, Wilson HR (1953) Nature 171:738–740. 3. Franklin RE, Gosling RG (1953) Nature 171:740–741.
Associate Professor Terry Mulhern is the Director of Teaching and Nobel Prize winners at the ceremony in Stockholm, Learning for Biochemistry and Sweden, 1962. From left: biophysicist Francis Crick, Molecular Biology in the School biophysicist Maurice Wilkins, writer John Steinbeck, of Biomedical Sciences at the geneticist James Watson, biochemist Max Perutz University of Melbourne. and biochemist John Kendrew. Photo: Granger. [email protected]
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Unexpected Journeys Through Different Research Lands and Scientific Families Paul Gleeson is the former Head of the Department of Biochemistry at the University of Melbourne. He is passionate cell biologist and advocate for basic science. His career has spanned over 35 years.
In this reflection, I will highlight some of my experiences genetic analysis. The conceptual puzzle of immunology which may be helpful for early career scientists to ensure was fun but at that stage cellular immunology was like you enjoy what you are doing and give yourself the best a house of cards. The doors of research were opened chance of success. The issues that have been striking by a summer vacation studentship at CSIRO Division for me have been the opportunity to work across a of Protein Chemistry with Lindsay Sparrow and Colin number of different disciplines and to interact with many Ward. I found that purifying proteins could be fun. people both locally and from different parts of the globe. I was an Honours student with Nancy Millis in the Collaborations are the key to an enjoyable research Microbiology Department at the University of Melbourne, career and optimising outcomes and opportunities. researching an industrial microbiology problem. Nancy was a notable pioneer in biotechnology in Australia and Early days one of the first women to be appointed to Professor. The people and environment were inspiring but I came to I grew up in the conservative Melbourne environment realise that I was more interested in molecules. Then, of the 50s and early 60s. International travel was via the connection as summer student, I was employed uncommon. My parents, who hadn’t travelled extensively, at CSIRO for two years as a research assistant with had the opportunity through my father’s work in the Michael Jermyn, an eclectic scientist and polymath. Mike paper manufacturing industry, to go overseas for eight introduced me to sugars and lectins. And by a stroke of months when I was seven years old. The six of us kids luck, Mike had a collaboration at Melbourne University were farmed out to various relatives and friends around with Adrienne Clarke and Bruce Knox in the School of Victoria for this period and I tracked the movements of Botany. I then joined their lab as a PhD student defining my parents across Europe and North America. It was all the structure and function of polysaccharides involved a mystery, but travel became implanted in my psyche as in fertilisation of flowering plants. The ecologists in the a must for my future. Botany School were alarmed that a PhD student in their I had excellent maths teachers at school, but other department did not have a major in botany! areas of science teaching were less inspiring. Although I It was the early days of Adrienne’s Clarke’s lab; she had no exposure to biology at school (it was not deemed went on to become a world leader in the field of self- a subject for an all boys’ school!), I found life sciences incompatibility in flowering plants and the chemistry fascinating. Basic genetics made a deep impression. of complex carbohydrates, as well as founding a I read The Double Helix by James Watson (1969) and significant biotechnology company. Adrienne cultivated found the creative drive and world of discovery thrilling. a strong team approach by nurturing interactions The idea of a life chasing intellectual pursuits, akin to the and collaborations, with minimal hierarchy. I worked ethereal Glass Bead Game by Herman Hesse (1946), alongside protein biochemists, optical and electron involving an abstract game of a synthesis of arts and microscopists and geneticists. Adrienne often reminded science, which I read several times, was very appealing. us of the central scientific questions being investigated and, if expert advice was needed beyond our sphere, Finding my way into research we were encouraged to venture out of our comfort zone. I studied Science at the University of Melbourne This multidisciplinary approach had a lasting influence without a clear grasp on what I wanted to do. for me on how science ought to be done. Biochemistry and Microbiology (with Immunology There was close association with the marine biologists integrated in those days) were my majors. Class sizes in the department and I was very fortunate to hitch a were small and practical classes were numerous. The memorable ride to Heron Island research station on their logic of biochemistry was satisfying; the architecture of field trips on two separate occasions. When opportunity organisms and mechanisms for survival and adaption knocks, take it! I learnt to scuba dive and we collected captivated me. The seeds for a future molecular cell Tridacna maxima clams from the reef (with permits!). biologist as I now reflect. Also, microbial genetics was Back in the lab, we purified a lectin from the Tridacna just beginning, and William Hayes’s book Genetics of haemolymph that was then used for a one-step affinity Bacteria and their Viruses (1969) described the fantastic purification of an arabinogalactan polysaccharide. So, power of bacteriophages and conjugation systems in my trip to Heron saved me about a year’s work purifying
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techniques. From Toronto, I then went to the National Institute of Medical Research at Mill Hill in London on a Beit Fellowship to work in Colin’s lab. Here, I expanded my work on carbohydrates and obtained experience in mammalian cell systems, generating lectin mutants, tracking toxins into intracellular endosomes, and characterising the total pool of N-glycans in mutant CHO cells with Jim Feeney using their newly installed 500 MHz NMR. The environment at Mill Hill was very conducive to meeting others; there was a bar in the institute where we would gather at the end of the day, and a squash court on site! I met many from outside the biochemistry division including developmental biologists, immunologists and parasitologists. I did not realise at the time but these networks had a strong impact on broadening my horizons. In 1984, I returned to Bruce Stone and Geoff Fincher’s Paul on Heron Island with marine biologists in 1977. labs at La Trobe to learn recombinant DNA techniques and a difficult polysaccharide. We closely collaborated with integrate back into the local science community. When I Bruce Stone’s lab at La Trobe University. Fellow students left Australia there were relatively few opportunities for between the two labs included Tony Bacic and Malcolm a research career. Four years later it was buzzing, with McConville; we became lifelong friends and years new research institutes being established. New early later we would find ourselves either supervising or be career fellowship schemes were appearing. This is an supervised by each other in leadership roles. At the time, important message in the cycles of research activity; it is never in my wildest imagination! hard to predict what the future holds in research funding and opportunities. The recent bushfires and coronavirus Postdoctoral experiences pandemic have raised the importance of science and scientists, in the general community. Following completion of my PhD in 1980, I became interested in synthesis of glycoproteins and wanted to move to a lab working on animal systems. Through Immunology comes into focus connections with Adrienne and Bruce Stone, I was My next piece of luck (in 1986) was an offer for a offered a postdoc from Harry Schachter in Toronto. three-year lectureship in the Department of Pathology Considering that I had not met Harry nor visited his and Immunology, Monash, at The Alfred hospital site, lab, it worked out amazingly well. However, I certainly by the incoming head, Jim Goding. This unexpected would encourage any graduate student to go and visit appointment came from a chance presentation of my their potential future labs and mentors. Harry was very work from Mill Hill at a local meeting organised by Jim. generous and he knew everyone in the field. It was He was keen to bring to his department people across an exciting time in the glycoprotein synthesis field and a range of disciplines. It was a great environment to my work resulted in the discovery of a Golgi-localised set up an independent lab as there were several young GlcNAc transferase involved in N-glycan synthesis of academic staff. I quickly realised that I would become branched complex N-glycans, using mass spectrometry isolated if I exclusively followed my previous research and NMR to characterise the products and enzyme interests and my best option was to collaborate with specificity. As with my PhD work, I put in long hours at others around the department. I become interested in the the lab but also used the opportunity to travel with my biochemical characterisation of autoantigens (gastric) partner Christine: we explored Canada from east to west. with Ban-Hock Toh. Via Harry’s connections and generosity in supporting his My lectures to students were initially focused on the ‘team’ members, I subsequently became the Australian biochemistry of immune molecules; staff also gave representative for the International Glycoconjugate weekly tutorials to third year immunology students. This Organization (IGO) and then organised GLYCO-19 was a crash course for me in updating my immunology meeting in Cairns in 2007. Relationships evolve and I spent considerable effort in learning the field. It was opportunities. the classic case of the blind leading the blind, but the I was keen to also experience the science culture in focus gave me great insight into challenges for students UK and Europe. Colin Hughes at the time was one of to learn the complexity, uncertainty and sometimes the foremost glycobiologists in the UK and his work contradictions in the immunology field. It demonstrated on the function of N-glycans, by generating and using the incredible value of teaching alongside research. lectin resistant mammalian cells, was attractive to me Teaching extended my interests into cellular as I would gain experience in emerging cell biology immunology of autoimmune diseases and, together with
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the newly arrived Ian van Driel and Frank Carbone in the the incoming students and postdocs and ensuring social department, we delved into the world of autoreactive T events are maintained. cells and CD25+ regulatory T cells, which were new kids on the immune block. Studying autoimmunity provided a The move to the University of Melbourne great challenge to all the underlying concepts in the field I think moving environments is a good idea as it of immunology. The partnership with Ian was particularly refreshes. After many good years at Monash Pathology important as we formed a joint team of an autoimmunity/ and Immunology, the administration ran into problems gastric biology program that would go on to produce a which permeated throughout the department. Suffice it series of papers and successful grants over more than to say that universities are not particularly good at fixing two decades. Also, I was able to keep up my specific things up when they go wrong; it is largely up to the interests in the Golgi apparatus, where I exploited the people at the coalface. Ironically, it was an experience environment and capitalised on screening and identifying that provided me with exceptional training for the future autoantibodies from patients with systemic autoimmune in what matters in helping to run a department. Later, I diseases to map new Golgi components that ultimately attended many leadership courses, but none matched led to defining trafficking pathways into and from the the on-the-ground experience dealing with problems. Golgi. Exposure to new fields enriches your research Luckily for us, the Department of Biochemistry at the ideas in very unexpected ways. University of Melbourne was looking to recruit two new staff. So, Ian and I applied as a joint team in 2001 and were successful, under the new departmental headship of Mary-Jane Gething. Little did we know at the time that two future heads of departments had just been appointed. The attraction was that the department was undergoing a generational change and that the future move into the soon to be constructed Bio21 Institute, driven by the outgoing Head, Dick Wettenhall. Bio21 would provide multidisciplinary opportunities, break down barriers and be in close proximity to industry. Our decision was about predicting where that environment would lead to in the longer term. There were major challenges in the move to bring many lines of mice into the facility and try to keep the needs of the individuals in the lab moving along. The challenges were greatly softened by having both of us working to sort out the problems, with the great support Artist’s rendition of the Golgi apparatus. from the departmental animal technician, Max Walker. By Chloe Gleeson, Paul’s daughter. We moved into Bio21 in 2004 and the research with Ian on autoreactive T cells continued for another two grant Students and postdocs: choose wisely cycles. Both of us were attracted into administrative I have been exceptionally fortunate with the quality of positions around the university and we gradually PhD students and postdocs in my lab. All have been developed different research areas provided within the very talented and terrific people to work with. There is a new environment. Research interests naturally evolve. temptation early on in your career to try to rapidly build up My own interest in membrane trafficking moved from the group. Don’t! Choose wisely. Academic performance model systems to Alzheimer’s disease with help from is just one measure. The individuals need to fit into the individuals in my immediate environment, especially culture of your team and be able to interact well together. through Andy Hill’s intellectual input, reagents and One misplaced individual will consume hours of your contacts and later with Danny Hatters. In Search of time to sort out the problems. I always include my lab Memory by Eric Kandel (2006) provided a wonderful team in the selection process by providing them the entree into the history of neuroscience. In addition, opportunity to meet the individuals (if not in person, by opportunities arose with industry within Bio21, and I Skype) and taking on board their feedback. I am proud have been fortunate in successfully obtaining a series of that all my PhD students have completed successfully. In ARC Linkage grants with CSL on the cell biology and addition to research, they have also gone off in a variety trafficking of the neonatal FcR receptor and the capacity of different careers (for example, genetic counselling, IT, to extend the half-life of novel therapeutic proteins. The epidemiology, teaching). The stability of my group has Golgi apparatus also remains a close friend and we are been dramatically enhanced by a long-term research exploring a number of new functions of this organelle assistant, Fiona Houghton. Fiona has stuck by the lab for that shows its ability to act as a cell sensor, akin to other more than 20 years and has provided support for all in intracellular organelles.
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Holidays I have always considered holidays to be important and I made sure that I took some. Research is intense often involving evening and weekend work. Holidays that take you to a different mindset and place are the best, and even a few days can make a difference, such as bush walking in the wilds of Tasmania. Find ways of doing this. When our kids were small, we took long service leave and travelled around Australia with our young children for ten weeks. From Heidelberg at EMBL we drove to a conference in Milan then onwards to southern France. During the period at the Curie we spent six weeks as a family in a small apartment in the Latin Quarter exploring Paris on foot. More recently, I have discovered a hotel specialising in cycling trips on the Adriatic coast of Italy. The Gleeson lab group in 2020. FAOBMB Head of Department An opportunity arose when the then ASBMB President, I agreed, initially reluctantly, to take over as head of Leann Tilley, invited me to consider the position of department in 2006 when Mary Jane Gething retired. ASBMB delegate for the FAOBMB. Australia has been My period as head for ten years was very busy and a very active participant in this Asian and Oceanian very rewarding. It is worth noting for younger scientists federation from its foundation nearly 50 years ago. This that in all our recruitment processes, the department has unexpectedly taken me into a new world. Delegates actively sought people who had demonstrated that they from 21 national societies in our region work together to are willing and able to collaborate with their peers from organise meetings, conferences and congresses, and day one. It was particularly rewarding to build up the encourage young scientists by various programs and research strength in the department by recruiting and awards. I am now Fellowship Chair of the FAOBMB and mentoring young/early career lab heads and to witness work closely with a wonderful group of people who are their well-deserved success with grants and fellowship generous with their time. My involvement has provided applications. It was also very satisfying to recruit and opportunities to visit regional countries, including Japan, support the teaching specialists in the department who Philippines, South Korea, China and Pakistan. This year now have the same opportunities to advance their would have been Sri Lanka, if not for COVID-19. It is very careers as the researchers. From the considerable impressive to meet young dedicated scientists working in support I received from other staff members, I was able very challenging environments. The funding for programs to keep my research group going during this period. I also via the FAOBMB makes a big difference to their career maintained a full undergraduate teaching load, as I think development and networking. There is probably more it essential to be engaged in this core university activity. I could add, especially to encourage involvement in Teaching enriches and generates research ideas. conference organising – maybe for another time. Sabbaticals Mini-sabbatical made a lasting impression on me. The standouts are six months at EMBL, Heidelberg, and three months at the Curie Institute, Paris. EMBL is like a big family and, as the majority of researchers are early career scientists from all over Europe, the network established blossoms for many years. My connection with the Curie also opened up an opportunity to become a member of the Human Program Science Program Fellowship committee, which I served on for four years. My strong advice is to visit places based not only on the specific lab, but also the broader environment and culture. FAOBMB Executive at the FAOBMB Conference held in Kuala Lumpur, Malaysia, in 2019.
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 39 ASBMB Boomerang Award Report
Australian Beer is CRISPR Spend enough time away from home and you start to miss the simplest of things
After completing my PhD with Professor Charles Bond and Associate Professor Archa Fox at the University of Western Australia in 2016, I relocated to the United States where I have been working as a postdoctoral fellow with Professor Jennifer Doudna at the University of California, Berkeley. By early 2019, I was searching for a conference that would take me back to Australia where I could present my recent work, catch up with family, and get my hands on a good lager! Originally from ASBMB Western Australia, I was excited to see that the ASBMB President 2019 meeting was going to be in Perth, and in Fremantle Joel Mackay no less (go the Dockers!). After registering and applying congratulates through the ASBMB, I was thrilled when I received the Gavin at email saying I had been awarded the 2019 ASBMB ASBMB 2019. Boomerang Award. What a great opportunity! With the generous support offered from the ASBMB, I was able to to sit down, beer in hand and watch the game with my plan a whirlwind trip across Australia, eager to pack in as family. After a few days of catching up, it was time for the much as I could while I was home. ASBMB 2019 meeting in Fremantle. In mid-September I flew across the Pacific to Melbourne My postdoctoral research has been focused on the where in rapid succession I presented my work at molecular evolution of CRISPR-Cas systems, a constant Monash University, St Vincent’s Institute and La Trobe evolutionary back and forth that has generated a plethora University. It was an absolute privilege to have the of biotechnologically applicable tools. To my delight, opportunity to present at each institute. Australia is home the first day of the ASBMB 2019 meeting featured to an incredible diversity of scientists and it was great to applications of CRISPR-Cas in cancer, gene discovery, network with colleagues who offered both great questions and even drug discovery in fungi! The ASBMB 2019 and critical feedback. After what was an incredible four meeting showcased the mechanistic elegance at the days in Melbourne (featuring a solid reintroduction to heart of biology but also the raw talent of both Australian Australian coffee, food and beer), I skipped across to and international scientists. It was an incredible honour Sydney where I presented my work at the Victor Chang to present my work amongst such a stellar array of Cardiac Research Institute. Come AFL Grand Final day, speakers and I cannot thank the ASBMB enough for their I jumped onto a plane bound for Perth, right on time support. Beyond the intellectually engaging science, it was a great opportunity to network with colleagues and revisit some old haunts from the PhD days. Before I knew it, the conference was over, everyone was headed back to work and I made my way back across Australia to San Francisco. It was an amazing trip back home: one that saw a healthy exposure to remarkable science, good times spent with friends and family, and perhaps an unhealthy exposure to the comforts of familiar food and beer. I cannot thank the ASBMB enough for the opportunity and their continued support. I eagerly look forward to my next trip back to Australia! Gavin Knott is a Research Fellow at Monash University, currently based at the University of California, Berkeley. Gavin enjoys dinner in Fremantle with ASBMB 2019 attendees.
PAGE 40 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Artificial Intelligence in Medicine – What is Patentable?
Continuing our series of more so than in the field of medicine. articles on intellectual ‘Deep’ networks (that perform ‘deep learning’) are property, Anthony Selleck, one of the key technical breakthroughs underlying Patent Attorney, FPA Patent modern artificial neural networks. In contrast to the flat Attorneys, discusses topology of earlier approaches, deep learning networks how advances in artificial are arranged in layers, each of which contains several intelligence in the medical thousand neurons. The first layer is fed with a large input field can be protected. dataset that contains examples of the phenomenon that the network is to model. In the medical domain, the input dataset could be any form of biomedical data, such as medical images with particular features, symptoms and associated diagnoses, candidate drug compounds and/ While the use of artificial intelligence (AI) in medicine or genomic data. has a long history, the last few years have seen an The system connects the neurons in the layers to perform explosion in interest and investment in this field of a structured sequence of computations that define a model technology. AI, and in particular, ‘machine learning’, is that can be used to make predictions from input data. The being applied to develop new products and processes robustness of the model is tested by running the input for use in both medical research and clinical practice. dataset through the neural network and determining how Patents are the classic species of intellectual property well it performed its task. Any deficiencies in the model rights used to protect medical innovations such as new are used to rearrange the connection patterns between pharmaceuticals, genetic technologies and medical the neurons and thereby improve the model’s accuracy. devices. However, when it comes to protecting AI-related Once the model converges to a desired level of accuracy innovation through the patent system, certain challenges (which may involve many iterations), the artificial neural remain. This article will examine the latest applications network is evaluated by processing a new dataset of of AI in medicine and provide guidance for identifying unseen values. This provides an indication of how the aspects of AI projects that may be protectable by patents. model might perform in the real world when processing data on which it has not been trained. AI and machine learning The term ‘artificial intelligence’ was coined in 1956 to Protecting AI innovations refer to computer programming techniques that seek to With the increase in the availability of medical imaging, mimic human intelligence. During the 1960s and 1970s, biomedical, genomic and epidemiological datasets, deep AI progressed into the development of ‘expert systems’, learning techniques are being harnessed to develop where computers were programmed to simulate the solutions across a range of medical domains. decision-making processes of human experts. Such Radiology is a natural application, where artificial neural systems were the first to apply AI to the realm of medicine networks can be readily trained with medical imaging by designing computer programs that would assist in the datasets to be able to recognise and essentially diagnose process of medical diagnosis. diseases captured in an image. In this regard, machine The 1980s and 1990s saw the development of a new learning algorithms are increasingly being integrated into approach known as ‘artificial neural networks’. These the workflow of radiology software to assist clinicians. are a network of computing units that are connected and More ambitiously, AI is being used in the task of drug controlled in a manner that (supposedly) resembles the discovery. In this application, the artificial neural network neurons in the human brain. Each neuron performs a is trained with suitable biomedical data in order to: small computational task (typically matrix multiplication) • Identify previously unknown disease mechanisms and communicates its results to other neurons. In and/or pathways; contrast to earlier approaches, the logical rules are not • Identify potential treatments on the basis of the ‘manually’ coded into the system. Instead, the artificial determined mechanisms; neural network derives the rules itself (and thus ‘learns’) • Generate more predictive hypotheses based on from a large dataset that is input to the system. patient-driven biology and genetic profiles. After a surge of interest, artificial neural networks fell However, these new approaches beg the question about out of favour by the end of the 1990s. However, starting what aspects of an AI project are potentially protectable in the early-2010s with some well-publicised advances through the patent system. In this regard, it is a cardinal in artificial neural network-assisted language translation, requirement before a patent will be granted that there is strong interest in the technology returned. The interest a new and non-obvious invention. Inventions involving and investment remains very much in place today, no new algorithms and computer software also tend to be
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 41 Artificial Intelligence in Medicine – What is Patentable? carefully scrutinised for compliance with the requirement AI as an inventor of ‘patentable subject matter’. In common with patents A recent issue that has arisen is whether an AI can make for certain classes of diagnostic method, AI patents are inventions itself, and thus should be named as such on sometimes rejected as being directed to a scientific a patent application. Attempts have already been made discovery rather than to a human-made invention. to file patent applications in the name of an AI inventor, While merely training an artificial neural network on a however these have been rejected by the UK and US new dataset is in itself unlikely to constitute a patentable patent offices. The UK Intellectual Property Office has invention, there is still broad scope for securing protection also now issued updated guidance to the effect that any over other aspects of an AI project. patent application which names an AI as the inventor will For example, changes made to the mathematical not be accepted, as the inventor must be ‘a person’. underpinnings of an artificial neural network – such The European Patent Office has also weighed into the as to improve its performance with particular types of issue by releasing guidance observing that AI systems biomedical data – are potentially patentable. Indeed, it ‘at present’ have no rights, and that ‘no … law has [yet] was the development of new underlying algorithms (and been determined which would recognise… an AI… as an especially in the field of back-propagation) that drove the inventor’. However, the EPO did not go so far as to say breakthroughs in deep learning technologies in the early that it would be impossible for any AI to be recognised as 2010s. an inventor in the future. Another area of potentially patentable technology is the development of artificial neural networks that generate the initial training datasets that are used by other neural Conclusions networks. This can be particularly important in the In light of the substantial investment involved in building investigation of rarer diseases and disease pathways for and deploying AI in a research or clinical context, careful which definitive datasets may not be available. consideration should be given to protecting as much of Techniques for ‘conditioning’ biomedical data to make it the underlying technology as possible. This requires a more amenable to serving as training data for an artificial sharp focus on the innovative aspects of the technology – neural network are also potentially patentable. In this either in the AI itself or in its integration with other systems regard, mathematical techniques to automatically classify and equipment – to ensure that commercially valuable and label digital images, videos, audio or speech signals patent rights are sought. In addition, if the technology based on low level features, could form the subject of a encompasses new algorithms, to head off an objection patentable invention. that the application is not directed to patentable subject Finally, there is broad scope for patentable invention to matter, it is important to include extensive disclosure of arise when AI systems are interfaced with other medical the practical applications for the new algorithms. equipment and devices. For example, use of a neural network in a heart-monitoring apparatus, or to drive digital [email protected] imaging systems, has the potential to be patentable.
Australian Society for Biochemistry and Molecular Biology Inc PUBLICATION SCHEDULE FOR AUSTRALIAN BIOCHEMIST, volume 51, 2020
Issue ASBMB Content Copy Deadline Issue Date
April 2020 51(1) Profiles of medal, award and fellowship winners Monday 10 February Monday 6 April Nominations for Executive/Council
August 2020 51(2) Nominations for medals, awards and fellowships Monday 8 June Monday 3 August Notice of AGM/proposed constitutional changes
December 2020 51(3) Annual reports/finances Monday 5 October Monday 30 November
PAGE 42 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Science Teachers’ Association of Victoria – Science Talent Search
The Victorian branch of the ASBMB continued its Gold Sponsorship of the annual Science Talent Search in October 2019. It was once again held at La Trobe University. This is a much cherished event on the school calendar for budding scientists. Founded in 1952, the event, organised by the Science Teachers’ Association of Victoria, is aimed at: • Encouraging students to consider the serious study of Sciences by encouraging independent project work amongst science students, providing students the opportunity to communicate their achievements to a wider audience and to enjoy recognition for their efforts and achievements. • Promoting the direct involvement of students in science and its communication. • Enabling public recognition of the quality of the work achieved in Science by Victorian students. The theme for 2019 was ‘Destination Moon: More Missions, More Science’. Students enrolled in Prep through to Year 12 were invited to submit projects in 10 categories: Computer Programs, Games, Science An award-winning student project Photography, Posters and Scientific Wall Charts, that depicts how the pancreas works. Working Models, Inventions, Experimental Research, Creative Writing, Video Productions and Class pesticide off kale?’ and ‘Maximising the amount of protein Experimental Research Project. The 3,271 young in yoghurt using different milk samples’. Perhaps some scientists who entered 2,327 submissions from 165 of us can tap into these young minds for inspiration for schools attest to the popularity of the event. our next round of NHMRC Ideas grants submissions? The Victorian Branch of the ASBMB supported the One of the most satisfying aspects serving as Victorian 2019 Science Talent Search with a $1,000 donation, State Representative is receiving hand-written and in the form of major and minor bursaries awarded to sometimes typed letters of appreciation from our young ten students from primary and high schools in Victoria. award recipients. Many express a desire to pursue a These schools included: Camberwell Girls Grammar future career in science and research. Their sincerity School, Genazzano FCJ College, Glen Eira College, and sense of appreciation in their meaningful messages Glendal Primary School, Paynesville Primary School, proves that our support of such events should be Presbyterian Ladies’ College, Sirius College and continued for many years to come. Strathcona Baptist Girls Grammar School. Project titles Erinna Lee included ‘Battle against the bacteria’, ‘The effect of ASBMB Victorian State Representative storage time on protein contents of Australian chicken www.sciencevictoria.com.au/sts eggs’, ‘What is the most effective method of removing
Assembly of our future scientists at the 2019 Science Teachers’ Association of Victoria Science Talent Search.
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 43 Australia Day Honour for ASBMB Member
Emeritus Professor Mitchell Guss was made an protein provided the first use of multi-wavelength Officer of the Order of Australia (AO) for distinguished anomalous diffraction (MAD) phasing to solve ade novo service to education and scientific research in the field of structure. molecular bioscience, and to professional organisations. On Hans’ formal retirement in 1994, Guss moved Professor Guss’ research is based on the determination the laboratory from the School of Chemistry to the of molecular structure, principally by the technique of Department of Biochemistry. Subsequent collaborations X-ray diffraction, and the relationship of the structures both within the University of Sydney, elsewhere in to chemical or biochemical function. Australia and internationally, resulted in many new It was his first Chemistry lecture as an undergraduate structures mostly of metallo-enzymes, including at the University of Sydney that drew Mitchell into the sulfatase, amine oxidase and proline aminopeptidase. world of protein structure, long before it was possible Professor Guss has been an Editor of Acta to apply the technique of crystallography to proteins in Crystallographica and the Journal of Molecular Australia. In that lecture, Professor Hans Freeman, later Biology. He has served as President of the Society of Guss’s Honours and PhD supervisor, drew attention to Crystallographers in Australia and New Zealand and the Nobel Prizes that had been awarded a few months of the Asian Crystallographic Association. He was a earlier to Perutz and Kendrew for protein structure and member of the International Union of Crystallography to Watson, Crick and Wilkins for the structure of DNA. executive for six years. His pioneering use of After five years as a postdoctoral fellow in the UK and synchrotron radiation sources led to appointments the USA, he returned to Australia to rejoin Freeman’s on scientific advisory committees for the NIH and the group, then attempting the first protein crystal structure Australian Synchrotron. in Australia. With Peter Colman and others, this effort He notes with thanks that his publications include more eventually resulted in the structure of plastocyanin, a than 200 co-authors who as students and collaborators ‘blue’ copper protein, providing an explanation for the have made the major contributions to the science that extraordinary spectroscopic and redox properties of this have enabled his award. family of proteins. Later work on another ‘blue’ copper
PAGE 44 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 In Memoriam
Robert Gerard (Gerry) Wake FAA 1933–2020 Gerry Wake made basic remainder of his career. On his way back to Australia, research the top priority Gerry spent six months in Oxford investigating the during his career (1953- reactivity of disulphide bonds in proteins with Rupert 2000). Research-led teaching Cecil. He and Aileen enjoyed Oxford so much that Gerry meant that undergraduate returned for a sabbatical in 1978 with Professor Joel students could be taught right Mandelstam. up to the cutting edge of the Gerry arrived back at the University of Sydney in late discipline. 1961. He continued with research on the biological When I arrived as a activity of κ-casein. Gerry and Buzz Baldwin had Lecturer in the Department of developed a procedure for the analysis of the mixture Biochemistry at the University of caseins present in milk micelles by starch–urea gel Gerry Wake. of Sydney in 1986, Gerry and electrophoresis, revealing a series of discrete bands Philip Kuchel were alternating and one enigmatic smear representing κ-casein. Heads of Department on a 2-year cycle. It was clear to Interestingly, κ-casein was behaving as an extremely me that they were the ‘dynamic duo’ in research and complex mixture of species defying conventional led from the front, gaining excellent research students analysis. Gerry had the insight to treat the κ-casein and substantial research grants. I was amongst the complex with disulphide bond-cleaving reagents to first of a new wave of academic staff that revitalised greatly simplify the electrophoretic pattern, revealing the Department; we were selected with research as the a finite number of protein species, which in different top priority under this dynamic leadership. The result combinations were giving rise to the great complexity was that over the period 1986–2010, our Department of the original pattern (upper image on next page). developed many powerful research programs. In more The purification of the individual κ-casein components recent times, much of this research talent has been provided the basis of the project for his first PhD student taken up by the Charles Perkins Centre. Tony Mackinlay. Further characterisation by his second Gerry undertook his BSc studies at the University PhD student, Ron Hill, including amino acid analysis of of Sydney, completing his Honours project in 1953 different regions of κ-casein molecules, provided one of on protein denaturation under the supervision of Dr the first recognitions of partitioning of polar and non-polar Hugh McKenzie of the CSIRO. Gerry continued to his amino acids within a protein. κ-Casein was functioning MSc then PhD in protein chemistry, under McKenzie’s as an amphiphile: analytical ultracentrifugation supervision, working on the caseins of milk and the showed that the hydrophobic N-terminal region of the stabilisation of casein micelles. McKenzie imparted molecule could interact with the other caseins whilst the the discipline characteristic of the physical sciences hydrophilic end (with one residue in three either Ser or and had a superbly equipped laboratory that included Thr), does not but rather provides a solvated water coat. an analytical ultracentrifuge. Gerry completed his PhD Rennin splits κ-casein once between the hydrophobic in 1958 and moved to the University of Wisconsin at and hydrophilic regions destabilising casein micelles Madison to work with Robert L (Buzz) Baldwin. leading to curds and whey. Buzz was only five years older than Gerry and already well known for his studies on ultracentrifugation. He was influential in developing Gerry’s approach to research and they remained lifelong friends. When Gerry and his wife Aileen arrived in Madison, the weather was extremely cold. Buzz was not there but had left a coat and scarf, one of many kindnesses extended to them during their two and a half years in the USA. After 6 months, Gerry moved with Buzz to Stanford University. Wake and Baldwin published papers together both on caseins and DNA replication. At Stanford, Arthur Kornberg had just published his pioneering work on the DNA polymerase from Escherichia coli for which he later received the Nobel Prize. The central aim at Stanford was always to understand biological systems at a molecular level, Gerry shared this priority and always advocated basic research. During the two years at Stanford, Gerry took up work on DNA replication that Gerry and Buzz Baldwin. became the field of research in which he excelled for the Photo: Ross Inman, Stanford University, 1961.
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 45 In Memoriam
Gerry’s subsequent research was focused on DNA synthesis in the bacterium, Bacillus subtilis, the movement of replication forks on the circular chromosomal DNA, and their arrest at completion of a cycle of DNA replication. In 1971, Gerry made a major discovery about replication of DNA in bacteria. Using a microscope and the technique of autoradiography, he determined the topology of DNA within a replicating multi-forked bacterial chromosome. He found that DNA synthesis occurred in both directions from a unique origin, rather than in one direction, as had been generally accepted (lower image, opposite). For this The enigmatic continuum of molecular species and other major contributions, Gerry was elected as a presented by κ-casein on starch-urea gel Fellow of the Australian Academy of Science in 1985. electrophoresis. His subsequent research focused on his dual fascination a. Analysis of κ-casein into a finite series of with the termination of chromosome replication and bands following reduction of disulphide bonds by cell division in B. subtilis. Tony Weiss, who was a PhD mercaptoethanol and alkylation under denaturing student in Gerry’s lab and is now the McCaughey Chair conditions employing b. 3 M guanidine hydrochloride in Biochemistry at Sydney University (formerly Gerry’s or c. 8 M urea. chair) fondly recalls the joy of being supervised by Reproduced from Hill RJ (1965) Studies on the action Gerry, and the excitement of identifying the replication of rennin on κ-casein. MSc thesis. University of Sydney. terminus terC on the bacterial chromosome. Gerry continued to lead this new field by characterising the roles and structure of the protein RTP (replication termination protein) that bound to terC. His 1995 review with long-term friend and colleague Jeff Errington FRS entitled ‘Chromosome partitioning in bacteria’ illuminated our fundamental understanding of the field. Gerry’s pioneering research aided the construction of the genetic and restriction site maps of B. subtilis which, in turn, guided the complete sequencing (by others) of the genome of B. subtilis, a forerunner to thousands of sequenced bacterial genomes. It has also contributed to our analysis of DNA replication in humans.
Gerry’s influential autoradiograph of symmetrically reinitiated chromosomes demonstrates bidirectional replication. Only the replicated DNA strands are radioactively labelled (unbroken lines in the scheme) Gerry receives the 25-year long service medal from Sir allowing only the replicated double-helical chromosomal Hermann Black, Chancellor, University of Sydney, 1984. regions to be visible in the autoradiograph. Reproduced with permission from Elsevier: Wake RG (1972) J Mol Biol 68:501–509.
PAGE 46 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 In Memoriam
One of Gerry’s greatest academic legacies lives on through the graduate students he trained in the art of scientific research. On arrival in his laboratory each student had some very general notions of the nature of research. Gerry taught by example that behind his beautiful and outstandingly elegant research there lay a concealed art: organisation, planning and an uncanny ability to look at complex phenomena to see underlying simpler mechanisms upon which one could focus investigations. The approaches he imparted led his students on to highly successful careers in research and teaching, many at professorial level and including directorships of research institutes. One year before Gerry’s retirement in 2000, while I was Head of School, I commissioned Judy Cassab (twice an Archibald Prize winner) to paint Gerry’s portrait. Gerry may have been initially a little doubtful, but the portrait was completed with six sittings at Judy’s house and was a wonderful experience for Gerry. They became good friends and the portrait displays many of Gerry’s attributes, a keen mind with penetrating eyes, long fingers useful for lab work, and the microscope with which he made his major discovery relating to bidirectional DNA replication. Gerry’s portrait hangs prominently in the Molecular Bioscience Building at the University of Sydney. Gerry gave his time generously to the Australian Gerry with the microscope he used to demonstrate scientific community. He served on Council of the bidirectional replication of the Bacilis subtilis Australian Academy of Science (1990–1993) and as chromosome. Portrait by Judy Cassab, 1999. Vice-President (1991–1992), as well as on the National Committee for Biochemistry and the Boden Research After his retirement, Gerry continued to play tennis Conferences selection committee. He was well known in regularly at Sydney University with a notable group of ARC grant circles in the 1980s for his travel to different scientific colleagues. In later years Gerry developed cities to interview applicants face to face. Gerry was Parkinson’s Disease, which he faced with great courage. Treasurer of the Australian Biochemical Society (1970– He was a very fine man, a loving husband to Aileen, a 1973) and served as President (1984–1986). devoted father to Rachel and Simon, father-in-law and grandfather. The extraordinary collection of scientists at Gerry’s funeral and the long list of former students and colleagues who provided condolences by email attest to his inspirational legacy. He was father and grandfather of a large scientific community. His human and scientific legacies will live on.
Richard Christopherson with the assistance of Ron Hill, Tony Weiss and Philip Kuchel
Three generations of the Wake family, 2017.
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 47 22–25 NOVEMBER 2021
We are excited to welcome you to Christchurch, New Zealand for the 16th Congress of the Federation of Asian and Oceanian Biochemists and Molecular Biologists.
This will also be ASBMB’s annual meeting in 2021.
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For further information visit FAOBMB2021.ORG PAGE 48 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Our Sustaining Members
ASBMB welcomes the following Disclaimer new Sustaining Member: The Australian Biochemist is Laboratories Credit Union (LCU) published by the Australian Society for Biochemistry and Molecular Biology Inc. The opinions expressed in this magazine do not necessarily represent the views of the Australian Society for Biochemistry and Molecular Biology Inc. The LI-6800 Portable Photosynthesis Unique Cell Biology Platform System represents a new era for More Physiologically in photosynthesis learning and Relevant In Vitro Studies discovery. The sensor head provides Alveole develop innovative tools for complete, automated control over the accelerating cell biology that enable environmental conditions your leaf is you to convert your existing microscope subjected to. Adjust temperature, CO 2 into an automated bioengineering concentration, humidity, light and flow system. Their technology allows rate for unprecedented plant physiology you to generate more reliable and LCU: Serving the Science insights. reproducible cell models that result in Improved plumbing in the sensor more physiologically relevant results. Community for Over 65 Years head, along with tighter tolerances on PRIMO was developed to enable you Laboratories Credit Union (LCU) was the gas analyzers and the CO2 mixer, founded in 1954 by a group of CSIRO TM to engineer custom microenvironments are all part of the Rapid Sensing for precise and controlled cellular employees who formed the credit union 22–25 Technology. These advancements studies. Their unique micropatterning with the aim of helping staff to gain unlock new research possibilities for device allows you to you to control access to finance. Back in those days you, including: the cellular environment in vitro with the loans were generally of small value NOVEMBER and were for things like the purchase of Fast Survey Measurements a wide range of applications including cell proliferation, migration and 3D white goods. Over the years the credit The LI-6800 achieves stability in as 2021 structural analysis. The Primo can union has grown and has been offering little as 45 seconds, for the fastest even be used for precise positioning home loans since the late 1980s and survey measurements of any portable of cells on TEM grids for consistent, now provides a full range of banking photosynthesis system – without reliable cryo-EM investigations. products to all members. We are excited to welcome you to sacrificing data accuracy or precision. Designed to be integrated onto most The main principle behind a credit Christchurch, New Zealand for the Small Plant Chamber inverted light microscopes and extend union is that every customer is an equal shareholder in the business, and The small plant chamber enables their capabilities the PRIMO integrates 16th Congress of the Federation of the profits go back to providing quality measurement of whole Arabidopsis with your existing imaging modalities products, better rates, fewer fees, thaliana plants, other small rosettes, for a total solution. Alternatively, AXT Asian and Oceanian Biochemists fantastic service as well as community or short canopies, such as turf. It is can supply it as a complete turnkey engagement projects. Every member and Molecular Biologists. compatible with the Large Light Source, solution with an imaging platform of can have a say in the governance of which lets you take measurements your choice. the organisation through the election of under controlled lighting using any This will also be ASBMB’s annual The Alveole system adds to AXT’s the board of directors. Plus they also combination of red, green, blue, and existing cell biology product portfolio come under the same legislation and white light. meeting in 2021. that includes standalone systems like regulators (APRA, ASIC, AUSTRAC, Integrated Gas Exchange and the Nanolive 3D holotomographic etc) as banks across Australia. Fluorescence microscope and the Phi Optics SLIM and GLIM quantitative phase imaging While LCU’s heritage is firmly linked The LI-6800 can make simultaneous add-ons that also provide analytical to CSIRO and their family and friends, Peak gas exchange and chlorophyll they are open to membership from Bodies capabilities for inverted microscopes. fluorescence measurements over the anyone living in the northern Sydney same leaf area. This allows you to AXT – Life Science Solutions suburbs or people who work for STEM study the role of alternative electron 02 9450 1359 organisations. sinks and to more accurately estimate [email protected] Hosts For more information contact: mesophyll conductance. www.lcu.com.au Learn more at www.licor.com/6800 [email protected] 02 9859 0550 For further information visit FAOBMB2021.ORG VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 49 Our Sustaining Members
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PAGE 50 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Our Sustaining Members
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VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 51 ASBMB Council 2020
PRESIDENT PRESIDENT ELECT Professor Joel Mackay Professor Jacqui Matthews School of Life and Environmental School of Life and Environmental Sciences Sciences University of Sydney University of Sydney SYDNEY NSW 2006 SYDNEY NSW 2006 Ph (02) 9351 3906 Ph (02) 9351 6025 Email: [email protected] Email: jacqueline.matthews@ sydney.edu.au
TREASURER SECRETARY Professor Marc Kvansakul Professor Briony Forbes Department of Biochemistry and Medicinal Biochemistry Genetics Flinders University La Trobe Institute for Molecular BEDFORD PARK SA 5042 Science Ph (08) 8204 4221 La Trobe University Email: [email protected] BUNDOORA VIC 3086 Ph (03) 9479 2263 Email: [email protected]
EDITOR and EDUCATION REPRESENTATIVE CHAIR OF COMMUNICATIONS Dr Nirma Samarawickrema Dr Tatiana Soares da Costa Department of Biochemistry and Department of Biochemistry and Molecular Biology Genetics Monash University La Trobe Institute for Molecular CLAYTON VIC 3800 Science Ph (03) 9902 0295 La Trobe University Email: nirma.samarawickrema@ BUNDOORA VIC 3086 monash.edu Ph (03) 9479 2227 Email: [email protected]
FAOBMB REPRESENTATIVE SECRETARY FOR Associate Professor Terrence SUSTAINING MEMBERS Piva Sally Jay School of Medical Sciences c/- ASBMB National Office RMIT University, PO Box 71 PO Box 2331 BUNDOORA VIC 3083 KENT TOWN SA 5071 Ph (03) 9925 6503 Ph (08) 8362 0009 Email: [email protected] Email: [email protected]
www.asbmb.org.au www.asbmb.org.au/combio2022
@ITSASBMB @ComBio2022 ComBio
PAGE 52 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020 Directory
COUNCIL FOR STATE SPECIAL INTEREST 2020 REPRESENTATIVES GROUPS PRESIDENT AUSTRALIAN CAPITAL TERRITORY ADELAIDE PROTEIN GROUP Professor Joel Mackay Dr Matthew Johnson Chair: Erin Brazel School of Life and Environmental Sciences Research School of Biology University of Adelaide University of Sydney Australian National University ADELAIDE SA 5005 SYDNEY NSW 2006 ACTON ACT 2601 Ph (08) 8313 8259 Ph (02) 9351 3906 Ph (02) 6127 0049 Email: [email protected] Email: [email protected] Email: [email protected] AUSTRALIAN YEAST GROUP PRESIDENT ELECT NEW SOUTH WALES Chair: Dr Alan Munn Professor Jacqui Matthews Dr Kate Quinlan Griffith University Gold Coast School of Life and Environmental Sciences School of Biotechnology and Biomolecular SOUTHPORT QLD 4222 University of Sydney Sciences Ph (07) 5552 9307 SYDNEY NSW 2006 University of New South Wales Email: [email protected] Ph (02) 9351 6025 SYDNEY 2052 NSW Email: [email protected] Ph (02) 9385 8586 BIOCHEMICAL EDUCATION Email: [email protected] Chair: Dr Nirma Samarawickrema TREASURER Monash University Professor Marc Kvansakul QUEENSLAND CLAYTON VIC 3800 Department of Biochemistry and Genetics Dr Benjamin Schulz Ph (03) 9902 0295 La Trobe Institute for Molecular Science School of Chemistry & Molecular Biosciences Email: [email protected] La Trobe University University of Queensland BUNDOORA VIC 3086 ST LUCIA QLD 4072 CELL ARCHITECTURE Ph (03) 9479 2263 Ph (07) 3365 4875 Chair: Associate Professor Thomas Fath Email: [email protected] Email: [email protected] Dementia Research Centre Macquarie University SECRETARY SOUTH AUSTRALIA NORTH RYDE NSW 2109 Professor Briony Forbes Dr Melissa Pitman Email: [email protected] Medicinal Biochemistry Centre for Cancer Biology Flinders University SA Pathology & University of South Australia MELBOURNE PROTEIN GROUP BEDFORD PARK SA 5042 ADELAIDE SA 5001 President: Dr Michael Griffin Ph (08) 8204 4221 Ph (08) 8302 7892 Biochemistry and Molecular Biology Email: [email protected] Email: [email protected] Bio21 Institute, University of Melbourne PARKVILLE VIC 3010 EDITOR and TASMANIA Ph (03) 9035 4233 CHAIR OF COMMUNICATIONS Dr Kate Brettingham-Moore Email: [email protected] Dr Tatiana Soares da Costa School of Medicine Department of Biochemistry and Genetics University of Tasmania METABOLISM AND MOLECULAR La Trobe Institute for Molecular Science HOBART TAS 7008 MEDICINE GROUP La Trobe University Ph (03) 6226 4609 Chair: Dr Nigel Turner BUNDOORA VIC 3086 Email: [email protected] UNSW Sydney Ph (03) 9479 2227 KENSINGTON NSW 2052 Email: [email protected] VICTORIA Ph (02) 9385 2548 Dr Erinna Lee Email: [email protected] EDUCATION REPRESENTATIVE Olivia Newton-John Cancer Research Institute Dr Nirma Samarawickrema 145 Studley Rd PERTH PROTEIN GROUP Department of Biochemistry and Molecular HEIDELBERG VIC 3084 Chair: Associate Professor Joshua Mylne Biology Ph (03) 9496 5726 University of Western Australia Monash University Email: [email protected] PERTH WA 6009 CLAYTON VIC 3800 Ph (08) 6488 4415 Ph (03) 9902 0295 WESTERN AUSTRALIA Email: [email protected] Email: [email protected] Dr Monika Murcha ARC Centre of Excellence in Plant Energy QUEENSLAND PROTEIN GROUP FAOBMB REPRESENTATIVE Biology Chair: Dr Brett Collins Associate Professor Terrence Piva University of Western Australia Institute for Molecular Bioscience, UQ School of Medical Sciences CRAWLEY WA 6009 ST LUCIA QLD 4072 RMIT University, PO Box 71 Ph (08) 6488 1749 Ph (07) 3346 2043 BUNDOORA VIC 3083 Email: [email protected] Email: [email protected] Ph (03) 9925 6503 Email: [email protected] ASBMB NATIONAL OFFICE RNA NETWORK AUSTRALASIA PO Box 2331 Chair: Dr Archa Fox SECRETARY FOR KENT TOWN SA 5071 Harry Perkins Institute of Medical Research SUSTAINING MEMBERS Ph (08) 8362 0009 NEDLANDS WA 6009 Sally Jay Fax (08) 8362 0009 Ph (08) 6151 0762 c/- ASBMB National Office Email: [email protected] Email: [email protected] PO Box 2331 http://www.asbmb.org.au KENT TOWN SA 5071 SYDNEY PROTEIN GROUP Ph (08) 8362 0009 President: Dr Tara Christie Email: [email protected] COPY DEADLINE FOR School of Life and Environmental Sciences NEXT ISSUE: University of Sydney SYDNEY NSW 2006 Monday 8 June 2020 Ph (02) 9685 9926 Email: [email protected]
VOL 51 NO 1 APRIL 2020 AUSTRALIAN BIOCHEMIST PAGE 53 PAGE 54 AUSTRALIAN BIOCHEMIST VOL 51 NO 1 APRIL 2020