Australian Biochemist
The Magazine of the Australian Society for Biochemistry and Molecular Biology Inc. December 2020, Volume 51, Number 3
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 1 ISSN 1443-0193 Table of Contents
3 Editorial Committee 4 From the President 5 ASBMB 2020 Meeting Reports 9 Publications with Impact Unravelling the Speciation, Trafficking, Autoinflammatory Potential of the Killer Protein, MLKL Fluid Coupling in the Rotary Motor of Life The Natural Function of a Multidrug Resistance Transporter Uncovering a New Way in Which Tumours Co-opt Their Microenvironments to Promote Disease Progression Mutational Landscape of Gall Bladder Cancers Structural Venomics: from Single to Double Knots and Everything in Between 19 ASBMB Education Feature Online Lessons From Our Students – 2020 ASBMB Education Symposium Ten Reasons to Crowdsource Exam Questions (and How to Do it Properly) Transitioning Case-based Biochemistry Workshops to Online During COVID-19 25 SDS Page A Beginner’s Guide to Milestone Preparation 27 Competition: Campus Visit 28 Perth Protein Group: an ASBMB Special Interest Group 29 Metabolism and Molecular Medicine: an ASBMB Special Interest Group 31 Off the Beaten Track Follow Your Dreams, Until Something Better Comes Along 32 ASBMB Member Wins Western Australian Premier’s Science Award 34 Intellectual Property Timing is Everything: When to Pull the Trigger on Patent Filing 37 News from the States 41 Great Expectations It’s Not Only What You Know, It’s Who Front Cover You Know – an Unplanned Career ASBMB President, Joel Mackay, 45 ASBMB Member Named Melburnian delivers the opening address at the 2020 of the Year ASBMB Research Symposium held online. 45 In Memoriam 47 ASBMB Annual Reports 51 Our Sustaining Members The Australian Biochemist Editor Tatiana Soares da Costa 56 ASBMB Council Editorial Officer Liana Friedman 57 Directory © 2020 Australian Society for Biochemistry and Molecular Biology Inc. All rights reserved.
PAGE 2 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 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 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 3 From the President
This piece is my swan song as ASBMB President, as One of our aims this I hand over the reins to Jacqui Matthews for the next year was to increase our two years. Jacqui will be well known to many of you involvement in science in the Australian biochemistry and molecular biology advocacy. We achieved community, particularly those of you who attend the an important first step in Lorne Conference on Protein Structure and Function. that direction – Tatiana Jacqui has just finished up her term as Chair of that Soares da Costa has meeting and was obviously looking for a new challenge! recently been elected to The last two years have seen some change at the the board of Science and ASBMB, particularly in our trialling of a new Society Technology Australia conference timetable. We decided to host an ASBMB- (STA) – the advocacy focussed meeting every two years and have ComBio group that represents only in the alternate years. We thought this might offer over 80,000 STEM members the opportunity to meet in a more intimate professionals, including venue than one of the large convention centres that we ASBMB’s members, to government – as the Biological need to use for ComBio meetings. Sciences Cluster Representative. We look forward to Our first ASBMB-only meeting was held in Perth in hearing from her about the role and about what we October 2019. Nic Taylor from the University of Western can do to further the cause of science on the political Australia put a huge effort into coordinating a team to agenda in Australia. run this meeting. The overall consensus amongst the What else have I been trying to do during my term as attendees was that it was a very enjoyable meeting with President? We have done quite a bit of ‘internal’ work, a good atmosphere and a great program. Attendance clarifying guidelines for State Representatives and at the meeting was lower than we would have hoped Special Interest Groups, providing State Representatives for, no doubt in part due to it being situated on the with a forum to connect with each other on a regular west coast, and possibly also partly due to uncertainty basis to exchange ideas, and reinvigorating the website on our part about the best way to focus the topics of (thanks to our webmaster Liana Friedman!). I would the meeting. When we were planning the meeting, we still like to survey members about the Society and to thought that highlighting a small number of topics in the consider whether we should coordinate an annual program (while still allowing talks in any subject area) meeting of Heads of Discipline in our field, as a way to might attract more attendees. With hindsight, we may share knowledge. I am hoping to organise these things have been wiser to not showcase particular subject before the end of 2020. areas, as it might have given the impression that other I’d like to finish off by giving enormous thanks to the topics would not be covered at all during the meeting. people who have contributed to ASBMB during my time We are still keen to see if we can get the ASBMB-only as President and who, without exception, have been format to work – scientifically and financially – and I think inspired, efficient, thorough and good humoured. Briony we will try to cast the net wider in future incarnations of Forbes and Dominic Ng have been stalwart Secretaries, the meeting. We will also seek feedback from members Marc Kvansakul has been a trustworthy Treasurer, to gauge their thoughts on meeting formats. Tatiana Soares da Costa, an energetic Editor (and Speaking of meetings, the online ASBMB symposia savvy social media specialist – follow @ITSASBMB on in September were a real success and it makes me Twitter), Liana Friedman, our expert Webmaster and wonder whether we could continue the momentum Editorial Officer, and Leann Tilley as Past President. with that format of having one or more short online And of course, Sally and Chris Jay have been the meetings (or even mixed live plus online, once that’s consummate professionals who have continued to hold permitted) as part of our regular offering (alongside it all together for us at the National Office – and have face-to-face conferences). I know most of us prefer the engaged with our ever-valuable Sustaining Members. face-to-face format, but there are some advantages in Jackie Wilce and Mark Hulett have allowed me to not terms of ease of organisation, low cost of attendance be concerned at all about the next ComBio, by doing and the opportunity to give more members a chance to a superb job of organising the one that will be held in present their work (particularly ECRs). The Education- Melbourne in 2022 (and locking in the 2020 Nobel Prize focussed meeting was particularly well attended, and in Chemistry Jennifer Doudna as a keynote speaker). I really would like to see us take advantage of that Leann has also strengthened our conference portfolio success to create a regular forum for presentations by leading a team to run the IUBMB Congress in and discussions in the biochemical education space. Melbourne in 2024. Having people doing great jobs like Encouraging the Society to increase its focus on this makes the role of the President infinitely easier! biochemistry education has been on my agenda, and Finally, thank you all too as members – you of course I am pleased that we have attracted an Education are the Society. See you all at the next meeting! Plenary speaker for ComBio2022. Joel Mackay President, ASBMB
PAGE 4 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 ASBMB 2020 Meeting
With the postponement of ComBio2020 until 2022, ASBMB hosted a virtual meeting in 2020. The ASBMB Council felt it was important to provide our members with opportunities to come together to maintain a sense community and celebrate our award winners. We held an Education Symposium chaired by Nirma Samarawickrema on 29 September and a Research Symposium chaired by Tatiana Soares da Costa on 30 September. Education Symposium
COVID-19 was the thunderbolt that hit our universities they experienced as a result of the sudden shift to remote in 2020 and forced educators into remote teaching. learning, the strategies they used to adapt, and their Biochemistry educators, like other educators worldwide, visions for a post-COVID learning environment. These scrambled behind the scenes, urgently transforming their presentations were timely reminders to educators of the teaching for online delivery while ensuring continuity, criticality of our ultimate audience – our students. quality and integrity. This unexpected and rapid transition to online remote learning resulted in the reinvention of much of our teaching and learning, and the adoption of a wealth of strategies and novel practices to engage students in workshops, tutorials, practical classes and assessment. The ASBMB Education Symposium – Teaching Remotely, Sharing Practice was held on 29 September 2020. The Education Symposium provided national and international participants a platform to share their insights and experiences, innovations and good practice Biochemistry students Ben Urzua and Rhianna Coscia. to transform the student learning experience as we move forward. The symposium had 250 registrants, with 131 from This event offered a mix of short and extended across Australia representing all six states and a territory presentations from educators who demonstrated how and 119 from overseas, many of whom were members of they: the Federation of Asian and Oceanian Biochemists and • Motivated students to learn online through game- Molecular Biologists (FAOBMB). based platforms, digital portfolios, Zoom case-study ASBMB President, Professor Joel Mackay, attributed workshops. the great level of participation in our event to the mutual • Transformed large face-to-face lab classes to online commitment and drive of biochemistry educators to laboratory classes without losing the interactivity enhance teaching practices and the value they place of the face-to-face classes by using a variety of on educating and inspiring our future generations of strategies including Zoom to guide a metabolomics scientists. This sentiment was echoed by Professor computer practical, PYMOL and Sketchfab to map Roger Daly (Head, Biochemistry and Molecular Biology, out and create guided tours of a protein. Monash University) in his welcome address. • Developed skills such as evaluative judgement, The symposium showcased a snapshot of the innovations research and writing skills through online implemented in remote learning. It is now up to the broader approaches. education community to reflect upon, adapt and apply this • Created authentic assessments even for large-scale learning as it is relevant to our specific student cohorts in undergraduate research experiences, and created a post-COVID world. Professor Liz Johnson (Deputy Vice- online assessments to avoid plagiarism through the Chancellor, Education, Deakin University) endorsed this development of software that could generate unique idea in her keynote address, Online is the New Normal: data sets. Teaching as We Work. “Disruption creates opportunity as Contributions from our students were a highlight of the assumptions and conventions are challenged. It is time conference. Third year student Benjamin Urzua (Monash to re-examine the value of each teaching mode and to University) and second year student Rhianna Coscia select learning and assessment activities that leverage (University of South Australia) discussed the challenges the strengths of online as well as face-to-face teaching.”
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 5 ASBMB 2020 Meeting
Keynote speaker Liz Johnson. Sophie Paquet-Fifield.
We congratulate the Education Symposium winners: We thank the ASBMB for supporting the vision of this Best abstract (sponsored by Fisher Biotec Australia) inaugural online symposium, Fisher Biotec for sponsoring Professor Gareth Denyer and Dr Alice Huang the best abstract award and Danielle Rika from the University of Sydney Department of Biochemistry and Molecular Biology, Generation of unique datasets to complement online Monash University, for her outstanding support to the practicals and build student experimental design and Education Symposium Committee and her meticulous troubleshooting skills attention to detail. As the ASBMB Education Symposium Organising Committee, we gratefully acknowledge each other and unanimously agree that we were a wonderful team! Our sincere thanks to our student participants, our presenters who shared their practice and to all who attended. The presentations highlight how educators rose to the challenge of remote teaching. Videos of the day’s presentations are available online.
ASBMB Education Symposium Organising Committee Gareth Denyer and Alice Huang. Nirma Samarawickrema, Monash University Tracey Kuit, University of Wollongong Highly Commended Abstract (sponsored by ASBMB) Amber Willems-Jones, University of Melbourne, Dr Kathryn Jones and Dr Monica Kan Matthew Clemson, University of Sydney University of Auckland, New Zealand Maurizio Costabile, University of South Australia Creating interactive online biochemistry laboratories using H5P
Kathryn Jones and Monica Kan. Best Zoom Background (sponsored by ASBMB) Dr Sophie Paquet-Fifield University of Melbourne For a background created collaboratively by her young children and students
PAGE 6 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 ASBMB 2020 Meeting Research Symposium
On 30 September, we held a Research Symposium, chaired by Tatiana Soares da Costa (ASBMB Editor and Chair of Communications) with the help of State Representatives: Benjamin Schulz, Erinna Lee, Kate Brettingham-Moore, Kate Quinlan, Melissa Pitman and Monika Murcha. We had an exciting Research Symposium program with two engaging plenary speakers. Professor Shelley Berger (University of Pennsylvania) started her talk discussing how epigenetic changes and pathways govern social behaviour in ants and ended with how chromatin enzymes modify the tumour suppressor p53. Professor National University) provided a great overview of the Glenn King (University of Queensland) gave a fascinating protein work his lab does, with a focus on the evolution talk on how a spider venom peptide can be used to treat of binding specificity in the amino acid binding proteins. ischemic injuries of the heart and brain. Eppendorf Edman ECR Award winner Professor Si Ming Man (Australian National University) discussed the role of GBPs in inflammasome activation. We also had lightening talks from ASBMB Travel Fellowship awardees, Dr Amy Baxter (La Trobe University), Dr Steffi Cheung (University of Melbourne), Dr Mengjie Hu (University of Melbourne) and Anukriti Mathur (Australian National University). The ASBMB AGM was held after lunch and with many of our members attending, we had no issues with reaching a quorum! Associate Professor Dominic Ng from the University of Queensland was elected as ASBMB National Secretary, taking over from Professor Briony Forbes, who we thanked for her many years of hard work and stewardship of the Society. The changing of the guard continued as we welcomed new State Representatives for ACT, NSW, QLD, TAS and VIC. At the conclusion of the symposium, we had a happy hour using Spatial Chat, which allowed us to ‘move around’ a crowd to join and leave conversations, replicating as much as possible the conference cocktail mixers we have sorely missed. Research Symposium attendance numbers were pleasing, with over 260 registrants from around Australia and overseas. The two-day ASBMB meeting highlighted the amazing advances our Australian biochemistry and molecular biology community is making in education and research. Thanks to the Organising Committee, the Presentations by plenary speakers Shelley Berger and award sponsors and ASBMB President, Joel Mackay, for Glenn King. their support. Videos of the day’s presentations are available online. We also heard from our 2020 ASBMB awardees. Planning continues for 2021, with an expanded East Lemberg medallist Professor Trevor Lithgow (Monash Coast Protein Meeting (more details in the coming University) described how porin loss leads to carbapenem months) and the FAOBMB Congress in Christchurch, resistance in Klebsiella. SDR Scientific Education Award New Zealand. We look forward to seeing you then – winner Dr Nirma Samarawickrema (Monash University) hopefully face-to-face! presented recommendations for education amidst COVID Tatiana Soares da Costa based on case studies. Boomerang Award winner Dr Chair, ASBMB 2020 Research Symposium Matthew Doyle (National Institutes of Health Bethesda) La Trobe Institute for Molecular Science discussed how BamA forms a translocation channel for La Trobe University secretion of bacterial autotransporter proteins. Shimadzu [email protected] Research medallist Professor Colin Jackson (Australian Twitter: @Tatiana_Biochem
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 7 PAGE 8 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 Publications with Impact
Publications with Impact profiles recent, high impact publications by ASBMB members. These short summaries showcase some of the latest research by presenting the work in a brief but accessible manner. If your work has recently been published in a high profile journal, please email [email protected]. Unravelling the Speciation, Trafficking, Autoinflammatory Potential of the Killer Protein, MLKL
Our team at the Walter and Eliza Hall Institute of Medical Research has published a trio of studies in Nature Communications that shed new light on the protein, MLKL, and how it causes an inflammatory form of cell death known as necroptosis. As outlined below, these studies use structural biology to understand evolutionary changes in MLKL, advanced microscopy to visualise when and where MLKL is activated in cells undergoing necroptosis, and genetic models to address how mutations in MLKL can trigger lethal auto-inflammatory disease.
Davies KA, Fitzgibbon C, Young SN, Garnish SE, Yeung W, Coursier D, Birkinshaw RW, Sandow JJ, Lehmann WIL, Liang LY, Lucet IS, Chalmers JD, Patrick WM, Kannan N, Petrie EJ, Czabotar PE*, Murphy JM*. Distinct pseudokinase domain conformations underlie divergent activation mechanisms among vertebrate MLKL orthologues. Nat Commun 2020;11:3060. *Corresponding authors: czabotar@wehi.edu.au, [email protected]
As a pseudokinase, MLKL is unable to catalyse phosphotransfer reactions. Instead, phosphorylation of MLKL’s activation loop by the upstream kinase, RIPK3, is thought to toggle a molecular switch, such that the killer N-terminal domain becomes exposed and can permeabilise the plasma membrane to induce cell death by necroptosis. The Crystal structures of the rat and horse MLKL pseudokinase domain, that were used to underlying mechanism better understand species compatibility. PDB: 6VBZ, 6VC0. was recently shown to differ between mouse and human necroptosis, which between MLKL orthologues where they could seldom led us to examine the extent of divergence among ‘talk’ to RIPK3 within mouse and human cells. Together, vertebrate MLKL orthologues. By studying nine MLKL our findings suggest that the MLKL:RIPK3 cassette has orthologues spanning multiple phylogenies, and solving rapidly co-evolved in different species, potentially due the structures of the rat and horse MLKL pseudokinase to varying selection pressures exerted by the pathogens domains, we identified a profound lack of compatibility that target each organism.
From left: André Samson, Joanne Hildebrand and Katherine Davies.
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 9 Publications with Impact
Samson AL*, Zhang Y, Geoghegan ND, Gavin XJ, Davies KA, Mlodzianoski MJ, Whitehead LW, Frank D, Garnish SE, Fitzgibbon C, Hempel A, Young SN, Jacobsen AV, Cawthorne W, Petrie EJ, Faux MC, Shield-Artin K, Lalaoui N, Hildebrand JM, Silke J, Rogers KL, Lessene G, Hawkins ED*, Murphy JM*. MLKL trafficking and accumulation at the plasma membrane control the kinetics and threshold for necroptosis. Nat Commun 2020;11:3151. *Corresponding authors: [email protected], [email protected], [email protected]
MLKL normally resides in the cytoplasm, but during necroptosis it translocates to membranes and kills cells by disrupting plasma membrane integrity. In this study, we used single-cell imaging to meticulously map the activation and relocation of endogenous human MLKL during necroptosis. We found that, once activated, MLKL moves to the plasma membrane via Golgi-, tubulin- and actin-dependent mechanisms, and that inhibiting these trafficking mechanisms specifically slows the onset of necroptotic cell death. Strikingly, during necroptosis, MLKL co-trafficks with tight junction proteins – proteins best known for their role in epithelial barrier formation. This co-trafficking allows MLKL to accumulate into micron-sized ‘hotpots’ at the plasma membrane during necroptosis. In this work, we identified two new rate- limiting checkpoints in necroptosis: (1) a trafficking Two cells undergoing necroptosis exemplifying the checkpoint that controls the movement of MLKL to junctional accumulation of human MLKL. the cell periphery, and (2) a junctional checkpoint that renders necroptosis ‘contagious’ and dictates the amount of MLKL needed at the plasma membrane to trigger cell death.
Hildebrand JM*, Kauppi M, Majewski IJ, Liu Z, Cox AJ, Miyake S, et al., Murphy JM, Alexander WS*, Silke J*. A missense mutation in the MLKL brace region promotes lethal neonatal inflammation and hematopoietic dysfunction. Nat Commun 2020;11:3150. *Corresponding authors: [email protected], [email protected], [email protected]
The signalling pathway that culminates in MLKL MLKL point mutant mouse strain (MlklD139V) in an ENU activation and killer activity has many entry and branch mutagenesis screen long before MLKL was implicated points, making it tough to tease apart the precise role of in necroptosis, where homozygous pups died soon after MLKL-mediated cell lysis in the aetiology of inflammation birth. Our team found that this point mutation conferred and disease. Serendipitously, our team identified a both constitutive activity to MLKL at the molecular level, but that this deadly activity was very efficiently ‘kept in check’ at the cellular level through MLKL proteolysis below a threshold. This threshold is overwhelmed only when two MlklD139V alleles are inherited, and only after birth – physiologically manifesting as inflammation in/ around the lower head and mediastinum (salivary glands, heart and thymus). We are excited to continue exploring the inflammatory role of a very closely situated cluster of human MLKL mutations which are present in An activating mutation in mouse MLKL manifests in a up to 8% of individuals globally, and enriched (in trans) deadly postnatal inflammatory syndrome. Longitudinal in a form of paediatric bone disease, CRMO. section of 2-day old mouse mediastinum.
Katherine Davies, André Samson, Joanne Hildebrand and James Murphy Walter and Eliza Hall Institute of Medical Research Department of Medical Biology, University of Melbourne
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Fluid Coupling in the Rotary Motor of Life
Sobti M, Walshe JL, Wu D, Ishmukhametov R, Zeng YC, Robinson CV, Berry RM, Stewart AG*.
Cryo-EM structures provide insight into how E. coli F1Fo ATP synthase accommodates symmetry mismatch. Nat Commun 2020;11:2615. *Corresponding author: [email protected]
F1Fo ATP synthase is a complex macromolecular machine consisting of two coupled rotary motors: the soluble F1 ATPase and the transmembrane
Fo motor. The F1 ATPase is a chemical motor that synthesises adenosine triphosphate (ATP), whereas the Fo motor is an electric motor powered by proton flow. Together these motors make a major contribution to the generation of cellular chemical energy by converting the proton motive force (pmf) into ATP, the universal cellular energy currency. By imaging the intact enzyme from Escherichia coli using cryo-electron microscopy (cryo-EM), the Stewart lab and their collaborators were able to generate detailed atomic-level information on how energy is transferred elastically between the two The Stewart laboratory, from left: James Walshe, Yi Zeng, motors. Alastair Stewart and Meghna Sobti. Recent improvements in cryo-EM have produced new insight on F1Fo ATP synthase, providing detailed resides in the membrane and is comprised of a ring of information about how this enzyme functions at the c-subunits (the c-ring) that can rotate relative to a stator, atomic level. Bacterial F1Fo ATP synthase has been the a-subunit. The motor is driven by the pmf, generated studied for many decades and has been used as a model by oxidative phosphorylation or photophosphorylation, system to understand ATP synthase function. The F1 and acts like a horizontal water wheel, with protons ATPase is comprised of a hexameric ring of alternating sequentially binding to the c-ring from the periplasm a- and b-subunits, with a single g subunit bound and rotating through it before being released into the asymmetrically in the ring centre. As this central ‘rotor’ cytoplasm. The rotation of the c-ring is transferred to the g-subunit rotates, it generates conformational changes central rotor (g subunit), thereby coupling the rotation of a b in the - and - subunits. The F1 ATPase enzyme one motor to the other. An interesting feature of almost operates with a binding-change mechanism, whereby all ATP synthases is a symmetry mismatch between the rotation of the central rotor induces sequential binding F1 and Fo motors because the F1 ATPase has threefold b of ADP and inorganic phosphate in the -subunits, rotational symmetry, whereas the Fo motor has tenfold which are then combined to make ATP. The Fo motor symmetry (in E. coli). This mismatch causes a non- The cryo-EM structure of
E. coli F1Fo ATP synthase. a. Sorting of the particles using 3D classification resulted in nine discrete sub-states. b. The sub-states show rotational ‘sub-stepping’
in the Fo motor, which is mediated by a flexible peripheral stalk. c. Local resolution of
the F1 ATPase and composition of the catalytic sites. d. Lipids (wheat density) bridge protein subunits
in the Fo motor.
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 11 Publications with Impact integral H+/ATP ratio and consequently, the motors need store elastic energy in the ‘peripheral’ stalk to overcome to be coupled elastically to operate efficiently. the symmetry mismatch between the two motors (b).
High resolution cryo-EM maps of the intact E. coli F1Fo High resolution information in the catalytic domain also
ATP synthase were generated by imaging the detergent- gave insight into how the F1 ATPase is inhibited from solubilised complex in the presence of MgADP. These operating in reverse (c), and maps focussing on just the maps highlighted nine different sub-states that described Fo motor showed a novel lipid interaction that can bridge the molecular motion of the complex, nucleotide binding a subunit within the c-ring with the stator a subunit (d), occupancy, and lipid-mediated interactions (see figure). thereby increasing the interaction surface which may Of greatest interest was the ‘sub-stepping’ observed in aid fluid coupling. the Fo motor, which showed how the transmembrane Alastair Stewart motor can rotate independently of the F1 ATPase and Victor Chang Cardiac Research Institute
The Natural Function of a Multidrug Resistance Transporter
Shafik SH, Cobbold SA, Barkat K, Richards SN, Lancaster NS, Llinás M, Hogg SJ, Summers RL, McConville MJ, Martin RE*. The natural function of the malaria parasite’s chloroquine resistance transporter. Nat Commun 2020;11:3922. *Corresponding author: [email protected]
“What is the natural function of the Plasmodium as a drug target. In this study, the Martin lab and falciparum chloroquine resistance transporter collaborators at the University of Melbourne and (PfCRT)?” has been a major unanswered question the Pennsylvania State University provide the long- in malaria parasite biology for two decades. awaited elucidation of PfCRT’s native substrates Mutations in PfCRT were originally identified as and normal physiological role. PfCRT functions the main cause of chloroquine resistance in P. to export host-derived peptides containing four to falciparum, but are now known to play a key role eleven residues from the digestive vacuole to the in multidrug resistance. The transporter resides at cytosol, thereby providing a source of amino acids the membrane of the parasite’s digestive vacuole for parasite metabolism and preventing the osmotic – a lysosomal-type organelle in which many stress of this organelle. antimalarial drugs accumulate, act, and/or are The malaria parasite consumes vast quantities of host activated. Mutant isoforms of PfCRT contribute proteins (mainly haemoglobin) to provide the space and to multidrug resistance primarily by transporting amino acids it requires for proliferation within the host drugs out the vacuole. PfCRT is also essential erythrocyte, and also to maintain the osmotic balance for parasite survival and has itself been identified of the parasitised cell. This process occurs within the
Wildtype (wt) PfCRT exports peptides from the digestive vacuole into the parasite cytosol. The diminished capacity of the drug resistance conferring isoform (mut) for peptide transport causes a build-up of peptides and amino acids, thereby raising the vacuole’s osmotic pressure and reducing the rate of digestion.
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eleven residues, varying in both charge and composition, are substrates of PfCRT in vitro and in situ. Furthermore, we showed that the protein does not transport other metabolites and/or organic or inorganic ions. The transport of peptides and peptide mimics via PfCRT is saturable, can be blocked by known PfCRT inhibitors Sarah (e.g. verapamil), and is dependent on protons as well as Shafik on a second solute that remains to be identified, but which (left) and is naturally present in the Xenopus oocyte. Relative to Rowena wildtype PfCRT, the drug resistance conferring isoforms Martin. exhibit reduced rates of peptide transport and accept a narrower range of peptides and peptide mimics. The acidic environment of the parasite’s digestive vacuole. reduced capacity of mutant PfCRT to efflux peptides Importantly, alterations to PfCRT can affect the normal out of the vacuole accounts for the accumulation of physiology of this organelle as well as the growth of the these substrate peptides in the drug resistant lines, and parasite. For example, downregulation of PfCRT causes explains the impaired fitness of parasites expressing the vacuole to swell and impairs parasite growth, and mutant isoforms of the transporter. The physiological potent inhibition of mutant PfCRT results in parasite relevance of this correlation was further substantiated death. Moreover, the mutant isoforms that confer drug when we used the peptidomic datasets to correctly resistance typically impose a fitness cost upon the predict host-derived peptides as being substrates or parasite, the severity of which is dependent upon the non-substrates of PfCRT. Our work indicates that the number and nature of the mutations. PfCRT-mediated transport of peptides from the vacuole Attempts to use heterologous expression systems to to the cytosol serves to (1) provide a source of amino identify the native substrates of PfCRT in vitro have acids to support the parasite’s high growth rate, and (2) produced wildly different ‘natural functions’ for the reduce peptide levels within the vacuole and thereby protein, with there being no convincing support for prevent the osmotic stress, swelling, and dysfunction one claim over the others. We employed the Xenopus of this organelle. The resolution of PfCRT’s native oocyte expression system, as well as measurements substrate-specificity and physiological role provides a of solute transport, drug activity, and metabolite levels foundation for the development of drugs that target both in isogenic parasite lines expressing different pfcrt its normal and drug resistance conferring functions. isoforms, to identify, and independently validate, the Rowena Martin natural substrates of PfCRT. Research School of Biology Our work revealed that host-derived peptides of four to Australian National University
Uncovering a New Way in Which Tumours Co-opt Their Microenvironments to Promote Disease Progression
Boyle ST, Poltavets V, Kular J, Pyne NT, Sandow JJ, Lewis AC, Murphy KJ, Kolesnikoff N, Moretti PAB, Tea MN, Tergaonkar V, Timpson P, Pitson SM, Webb AI, Whitfield RJ, Lopez AF, Kochetkova M*, Samuel MS*. ROCK-mediated selective activation of PERK signalling causes fibroblast reprogramming and tumour progression through a CRELD2-dependent mechanism. Nat Cell Biol 2020 22(7):882–895. *Corresponding authors: [email protected], [email protected]
Cancer-associated fibroblasts (CAFs) have been Rho-ROCK pathway with the tumour secretome reported to exhibit context-dependent tumour- while revealing a novel tumour-promoting role for promoting or tumour-suppressing capacities. PERK signalling and the enigmatic EGF domain- However, the mechanisms underpinning these containing protein CRELD2. contexts are not precisely defined. In collaboration Cancer cells need to modify and remodel the with other researchers at the Centre for Cancer environments within which they arise in order to facilitate Biology, the Walter and Eliza Hall Institute of Medical their survival, and to enhance their growth and spread. Research, the Garvan Institute of Medical Research This is because the normal tissue microenvironment and the A*STAR Institute of Molecular Cell Biology, is hostile to the survival and persistence of abnormal the Samuel lab at the Centre for Cancer Biology cells. To establish a permissive environment, cancer has defined a novel signalling axis connecting the cells therefore need to influence the behaviour of their
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 13 Publications with Impact
Exposure to Creld2 enhances the capacity of cancer- associated fibroblasts to promote tumour progression when they are orthotopically co-engrafted with primary mammary tumour cells into immune-competent hosts. Creld2 is secreted by tumour cells in which ROCK is activated, via a novel mechanism by which the PERK-regulated arm of the unfolded protein response is specifically engaged in the absence of ER-stress. genetically normal microenvironment. Herein lies a key ECM, the bulk of the tumour ECM is secreted by cells vulnerability. Since cancer cells need to persistently populating the microenvironment, such as fibroblasts maintain their influence over normal cells, interfering and some immune cells. with the signals passing between cancer cells and the To test the hypothesis that cancer cells influence microenvironment may provide us with opportunities to the behaviour of fibroblasts via secreted factors, we normalise the microenvironment such that it is no longer exposed primary mammary tumour fibroblasts from the a permissive one. MMTV-PyMT model of mammary cancer to medium We had previously demonstrated that the Rho-ROCK conditioned either by primary mammary tumour cells signalling pathway, which is frequently activated in in which the ROCK pathway was activated via the epithelial cancers, lies upstream of key changes expression of a construct encoding conditionally active within the microenvironment. In particular, tumours in ROCK, or control cells containing a version of the same which this pathway was activated had high levels of construct encoding kinase-dead ROCK. Fibroblasts collagen and other extracellular matrix (ECM) proteins, exposed to medium conditioned by tumour cells in enhancing their mechanical stiffness. Elevated tissue which ROCK had been activated exhibited induction of stiffness is strongly associated with disease progression, genes encoding ECM proteins and markers associated perpetuated by mechano-transduction signalling in with tumour-promoting CAFs. These fibroblasts were tumour cells that are located within stiff tissues. These also more motile than control fibroblasts and cell- signalling pathways, including signalling via YAP/ derived matrix prepared from them elicited collective TAZ, beta-catenin and FAK, regulate key processes and organised migration in tumour cells. Fibroblasts that that facilitate tumour cell survival, proliferation and had been exposed to medium conditioned by primary migration. However, a key question raised by these mammary tumour cells, in which ROCK was activated, observations was how Rho-ROCK signalling within enhanced the growth of tumours when co-engrafted with tumour cells resulted in the production of large amounts primary PyMT tumour cells into the mammary fat pads of ECM proteins. While tumour cells do indeed produce of wildtype, immune-competent FVB/n female mice.
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To identify the secreted factors that may be responsible (ER)-stress. Surprisingly but satisfyingly, recombinant for inducing the tumour-promoting characteristics in Creld2 was able to recapitulate the effect of ROCK- mammary tumour fibroblasts, we conducted proteomic conditioned medium on mammary tumour fibroblasts, analysis of the secretome of primary PyMT mammary rendering them tumour-promoting. tumour cells in which ROCK had been activated, and Analysis of signalling downstream of ROCK revealed compared this with the secretome of primary PyMT that cells in which ROCK was activated exhibited mammary tumour cells expressing kinase-dead ROCK. phosphorylation and activation of Perk, a key sensor Among the differentially secreted proteins was Creld2, of ER-stress in one arm of the unfolded protein a relatively obscure protein that was known to be response, and indeed that signalling downstream of secreted by cells subjected to endoplasmic reticulum Perk was engaged in these cells. Signalling through Perk increased the levels and nuclear translocation of the transcription factor Atf4, which we demonstrated to transcriptionally regulate the gene encoding Creld2. This explained the increased production of Creld2 by cells in which ROCK was activated. Inducing ER-stress in cancers to precipitate UPR- mediated immunogenic cell death is an approach that is currently the focus of translational research as a cancer therapy. Our work therefore serves as a timely warning that this approach may yield the unintended consequence of enhancing tumour progression via the generation of tumour-promoting CAFs. Sarah Boyle, Marina Kochetkova and Michael Samuel, Centre for Cancer Biology SA Pathology and University of South Australia Sarah Boyle, Marina Kochetkova and Michael Samuel.
Mutational Landscape of Gall Bladder Cancers
Pandey A*#, Stawiski EW*#, Durinck S#, Gowda H#, Goldstein LD, Barbhuiya MA, Schroder M, Sreenivasamurthy SK, Kim S, Phalke S, Suryamohan K, Lee K, Chakraborty P, Kode V, Shi X, Chatterjee A, Datta K, Khan AA, Subbannayya T, Wang J, Chaudhuri S, Gupta S, Srivastav BR, Jaiswal BS, Poojary SS, Bhunia S, Garcia P, Bizama C, Rosa L, Kwon W, Kim H, Han Y, Yadav TD, Ramprasad VL, Chaudhuri A, Modrusan Z, Roa JC, Tiwari PK, Jang J-Y*, Seshagiri S*. Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate. Nat Commun 2020;11:4225. *Corresponding authors: [email protected], [email protected], [email protected], [email protected]
Gall bladder cancer (GBC) is an aggressive characterise genomic alterations associated with gastrointestinal malignancy with a poor prognosis. GBC. A total of 167 GBC samples and 39 gall bladder GBC incidence rates are particularly high in specific non-neoplastic lesions with corresponding matched geographic regions of the world including Chile, normal tissue were sequenced. This enabled us to Bolivia, Peru, Korea, Japan and India. Reasons for identify genomic alterations frequently observed in higher incidence rates in these regions remains GBC and determine if there were differences among unclear. Women are two to six times more at risk of tumors from different geographic regions. GBC than men. The median survival of patients with We identified several significantly mutated genes GBC is generally less than a year. This is mainly that were not previously linked to GBC. This included because GBC patients are diagnosed at an advanced ELF3, a frequently mutated gene in GBC with genomic stage of the disease. Cholelithiasis and cholecystitis alterations in 21% of tumors. We integrated somatic are some of the well-known risk factors of GBC. mutation, copy number variation and gene fusion data to We established an international collaboration identify affected pathways in GBC. TP53/RB1 pathway between researchers from India, USA, South Korea was most commonly altered in GBC. We also observed and Chile, and performed whole genome, exome WNT pathway and KEAP1/NFE2L2 pathway activation and transcriptome sequencing to identify and in GBC. Activating mutations in CTNNB1 and RSPO3
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 15 Publications with Impact fusion were primary drivers of WNT pathway activation. We found inactivating mutations in SWI/SNF pathway genes including SMARCA4, ARID1A and ARID2. We also identified therapeutically actionable mutations in RAS/PI3K pathway involving frequent alterations in ERBB2, ERBB3, BRAF and PIK3CA. About 20% of all tumors sequenced in our study had actionable mutations based on approved therapies catalogued in OncoKB. Immunotherapy has revolutionised cancer treatment. Significant survival benefits have been observed in various cancers including melanoma and lung cancer. For the first time, we report GBC patients with mismatch repair defects who have characteristic high mutation burden and are candidates for check-point immunotherapy. To further determine the presence of cancer neoantigens that can be used either alone or in Significantly mutated genes in gall bladder cancer. combination with check-point inhibitors, we evaluated non-synonymous somatic mutations as candidate the potential to use cancer immunotherapy for treating neoantigens. Our analysis identified an average of 15 GBC. Beside serving as a resource for further studying neoantigens/tumor that were predicted to have high- GBC and developing therapies, our dataset identified affinity for MHC class I. Most predicted neoantigens many actionable GBC alterations that can be treated were derived from frequently mutated genes such as using approved therapies. TP53, ELF3, CTNNB1, ERBB2, ARID1A and CDKN2A. Harsha Gowda Using peripheral blood mononuclear cells from HLA- QIMR Berghofer Medical Research Institute matched healthy donors, we determined the ability of mutant peptides to activate T-cells. Mutant peptides from ELF3, ERBB2 and TP53 were found to activate T-cells Left: suggesting that these peptides are potential cancer Harsha vaccine candidates. Some of the ELF3 neoantigens can Gowda. be used as a common cancer vaccine candidate as they are recurrent mutations in GBC and other cancers such Right: as colon cancer and ampullary carcinomas. Somasekar Our comprehensive study identifies for the first time Seshagiri. Structural Venomics: from Single to Double Knots and Everything in Between
Pineda SS#*, Chin YKY#, Undheim EAB, Senff S, Mobli M, Dauly C, Escoubas P, Nicholson GM, Kass Q, Guo S, Herzig V, Mattick JS, King GF*. Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene. Proc Natl Acad Sci USA 2020;117(21):11399–11408. #Equal first authors *Corresponding authors: [email protected], [email protected]
Spiders and other venomous animals depend on underpinnings of venom complexity. We found that the production of complex venoms for defence, the venom of the Australian funnel-web spiders prey capture and competitor deterrence. Most evolved primarily by duplication and structural spider venoms are dominated by disulfide-rich elaboration a single ancestral knottin gene. peptides with molecular masses of 3–8 kDa. Spiders evolved from an arachnid ancestor around However, the mechanisms employed by spiders to 450 million years ago (1). Currently, there are more than generate such chemically and pharmacologically 100,000 extant species of spiders, making them one diverse venom cocktails is not well understood. of the most successful animal lineages on the planet. To address this question, we combined omics and Like other venomous invertebrates, spiders rely on their structural biology techniques, a new approach that venom to capture prey and defend themselves against we coined ‘structural venomics’, to investigate the predators. The ongoing battle between venomous
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Structural innovations in spider venoms knottins. Overview of toxin and protein superfamilies highlighting the main mechanisms by which toxins have been duplicated, conjugated and elaborated upon to form the diversity of knottin scaffolds found in venom of the Australian funnel-web spider H. infensa. In all structures, disulfide bonds are shown as red tubes, b-sheets and a-helices are highlighted in blue and green, respectively. Insert: Structural alignment of the core knottin regions of DRPs from superfamilies 1 (green), 6 (purple), 17 (pink), 22 (yellow) and 23 (orange), highlighting conservation of the knottin motif (disulfide-directed b-hairpin in the case of 22) and irrespective of the elaborations outside the core region. animals and their prey and predators places a constant selection pressure on venom efficacy, and over millions of years this has resulted in complex arsenals of venom compounds that vary in size and pharmacological activity. Spider venoms are dominated by ‘short’ (2–5 kDa) and ‘long’ (6–9 kDa) disulfide-rich peptides (DRPs). Most spider-venom DRP structures solved to date correspond to ‘short’ peptides that contain a knottin motif in which three disulfide bonds are arranged in a pseudo-knot configuration. The venom of the Australian funnel-web spider Hadronyche infensa is one of the most complex chemical arsenals in the natural world, comprising >3000 peptide toxins. We used a combined proteomic, transcriptomic and structural biology approach to explore the mechanism by which these spiders evolved such complex toxin repertoires. We showed that H. infensa produces 33 superfamilies of venom peptides From left: Sandy Pineda, Yanni Chin and Glenn King. and proteins, and that 26 these superfamilies are DRPs. Moreover, 15 of these DRPs contribute to >90% of the venom proteome. Structure elucidation using Sandy Pineda NMR spectroscopy revealed that most of the DRPs Institute for Molecular Bioscience are structurally related but present a range of structural University of Queensland innovations. The structural diversity ranged from DRPs Current affilitation: with a simple knottin motif to highly elaborated knottin Brain and Mind Centre domains and double-knot domains. Remarkably, this University of Sydney work enabled us to conclude that the incredible diversity Reference of DRPs in the venom of Australian funnel-web spiders 1. Lozano-Fernadez J, et al. (2016) Philos Trans R Soc is largely derived from a single ancestral knottin gene. Lond B Biol Sci 371:20150133.
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 17 AFFORDABLE FAST EASY-TO-USE CONTACT US FOR A DEMO
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The ASBMB Education Feature is coordinated by Nirma Samarawickrema ([email protected]) and Tracey Kuit ([email protected]).
Online Lessons from Our Students – 2020 ASBMB Education Symposium Tracey Kuit (University of Wollongong) and Amber Willems-Jones • UNMATCHED ACCURACY 1% Coefficient of Variation (University of Melbourne) interview undergraduate • LARGEST COUNTING VOLUME Biochemistry students Benjamin Urzua and Rhianna Coscia 5 µL (10 times that of conventional cell counters) At the recent 2020 ASBMB Education Symposium, connected and up-to-date was an important adaptation, • MULTI-SLIDE FOR MAXIMUM THROUGHPUT a student panel was held with two undergraduate as was talking to my friends for encouragement. This students: Benjamin Urzua, a third year Bachelor of helped to put everything in perspective and helped me Disposable slide (1,2,3,8 channels) Science/Bachelor of Arts student at Monash University to persevere. • OPTIMISED FOR BIOPROCESS & 21 CFR Part 11 and Rhianna Coscia, a second year Bachelor of Medical Rhianna – Generally, I adapted well to the transition Science student at the University of South Australia. online. A strategy I utilised was to stick to my timetable Built-in quality control & precision validation Rhianna and Ben shared their experiences learning as if teaching were on campus. This allowed me to keep biochemistry online in 2020. Responses to questions up-to-date with lectures and have tutorial answers ready have been paraphrased and condensed with permission. to go for the tutorial Zoom session. The early release Dual Fluorescence and Brightfield cell counting with Auto-focus of lecture recordings was really valuable as I could get ahead in my study, allowing ample time for content revision at the end of semester.
What helped you keep engaged online? Ben – Online Q&A Zoom sessions after a set of lectures Biochemistry were very useful to clarify understanding. Having students Ben small group online breakout rooms during the tutorial Urzua (left) and sessions, then coming back to the main large group to Rhianna Coscia. share our answers. Fresh lectures, rather than the use of pre-recorded lectures from previous years, were more engaging. Online laboratories remained one of the most What were the challenges or difficulties with the engaging aspects of online learning. rapid move to online learning in 2020? Rhianna – I appreciated the recording of classes Ben – My main difficulties were keeping to a schedule, delivered online. Whilst I joined classes live, recordings Reliable, High Speed Results Across a Wide Concentration Range maintaining a sense of reality and having a sense of allowed access at any time, and assisted revision. accomplishment. It was challenging not having the Though, seeing my tutors or lecturers’ faces whilst chance to interact with other students, though small they conveyed the information on Zoom really assisted TM LUNA-FL TM group breakout rooms online were the most useful tool in keeping me engaged, as seeing hand gestures and DUAL FLUORESCENCE LIVE/DEAD CELL COUNT IN 7SEC LUNA CELL COUNTER MANUAL to overcome this problem of reduced student interaction. models provided a human element to what was a very CELL COUNTER ADVANCED DECLUSTERING Rhianna – Challenges included ensuring my home was technologically driven environment. suitably set up for a home study environment, quiet and USER-FRIENDLY INTERFACE with reliable internet. An unexpected challenge was the What were the unexpected benefits of online difficulty of taking a break from online studies. With all practical classes? SIMPLE RECORDKEEPING events cancelled, I found myself spending extended Ben – Unexpectedly, the practical classes were the LOWEST COST, HIGHEST ACCURACY periods of time on university work without a break. As favourite part of my units. They encouraged me to become online learning continued, I overcame this by taking a more active learner in the process and to understand the regular breaks throughout my day. I felt more focussed protocols, why each reagent was important and to simply after incorporating this. be more curious. An online quiz prior to the start of the FREE COUNTING SLIDES OFFER — LIMITED TIME ONLY lab ensured we understood the different techniques we With every purchase of LUNA and LUNA-FL cell counter. How did you adapt to learning online? were going ‘to do’. During the lab, we would go through Valid to 31st December 2020. Ben – I adapted quite well, though it wasn’t until the each protocol step while we were asked questions. At last period of the first semester that I felt that what I had the end of each session, we had a quiz to complete. This CONTACT US FOR MORE INFORMATION accomplished so far was due to my own merit. Staying unexpected benefit in deeper learning may have been ATA Scientific Pty Ltd | [email protected] | www.atascientific.com.au | +61 29541 3500 VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 19 ASBMB Education Feature because we had more time to focus on what we were Zoom sessions/forums to allow the social interaction and doing as opposed to rushing to finish everything during a networking of students, separate to direct class work, traditional laboratory session. may also assist the online university experience. Rhianna – Moving practical classes online was naturally very disappointing, because undertaking a science What are your recommendations for educators? degree, the practical, hands on skills are very transferable Ben – Combining an educational format of self-taught/ to the workplace. However, the transition of practical self-paced online activities with face-to-face or online classes to the online environment was successful. We discussions, where students are encouraged to had a range of online materials and interactive activities come prepared with the lecture content and have the which substituted the face-to-face practicals. This opportunity to go beyond it. Secondly, having activities included practical videos which allowed us to visualise in which students depend on the participation of other what we would have been doing in the practical session, students, e.g. there could be some group activities where but also provided greater understanding to how supplied each student needs to contribute something by having sample results were obtained from recipe-like steps in a completed a task prior to the lecture/tutorial. This could lab book. help students to become more active learners and to collaborate. What were your frustrations with online learning? Rhianna – Continuing to offer online interactive activities Ben – I understand that collusion can be an issue and to supplement face-to-face learning, as it provides that having your notes by your side is an impediment instantaneous feedback about content understanding, to reliably measure how students are able to apply the and allows access at time of need. Secondly, consider unit’s content. However, sometimes test time constraints communication between teaching staff and students a meant we didn’t have enough time to show our true key importance when delivering learning online. There potential. Additionally, it was frustrating not being able to have been occasions in some classes where we have draw reaction mechanisms or biochemical pathways. not been contacted by educators, leaving students in Rhianna – Rather than a frustration as such, the limbo about what to do, what time to log on etc., causing reliability of the online assessment platform was anxiety undue stress. Thirdly, adhere to the timetable, utilising inducing. For example, in one particular test, my internet visual elements and interactive activities (e.g. Kahoot) to connection dropped out due to the number of students maintain the focus of students who are at home. logging on simultaneously. This caused additional anxiety in a test setting. There are technological aspects of online learning (i.e. countdown time limits, file compatibility, etc.) that can occasionally be unreliable. Tracey Kuit is an Education- Focused Associate Professor What things would you change? in the School of Chemistry Ben – Having more instances for students to engage and Molecular Bioscience, with one another. For example, providing online readings University of Wollongong. or short videos related to lectures and giving students [email protected] a chance to discuss with the lecturer and develop their critical thinking skills. I would be cautious, however, not to expect too much from students, because sometimes it felt that because students were at home, academics assumed they had more time and therefore gave an Dr Amber Willems-Jones increased workload as a result. is a Senior Lecturer in the Rhianna – As someone that likes to be organised and get Department of Biochemistry ahead in my studies, I value the upload of content early and Molecular Biology, to have efficient revision time at the end of semester. University of Melbourne. Online discussion forums also permit students to interact [email protected] with one another about content-related questions. Some
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Ten Reasons to Crowdsource Exam Questions (and How to Do it Properly) Alice Huang, Gareth Denyer, Matthew Clemson and Giselle Yeo, School of Life and Environmental Sciences, University of Sydney
For any academic who has ever been daunted 4. Questions thoroughly cover, and are well-aligned by the challenge of designing unique, relevant and to, course learning outcomes effective exam questions semester after semester – we It is easier for the cohort to collectively cover all learning propose a solution. PeerWise is an online repository of outcomes than it is for a single person. Assigning a student-authored questions used globally in over 1500 learning outcome to each student focuses their efforts institutions. For the last six years, we have integrated and ensures that their questions directly align with your PeerWise into our biochemistry courses at the University course. Questions pitched at a suitable granularity can of Sydney to promote discussion and collaboration only be created by participants intimately familiar with amongst students. With moderate organisation, the the course, which deters contract cheating. student cohort collectively generates a pool of thousands of questions, which can be modified to be exam-quality. 5. Questions spotlight student insights or While time and effort need to be invested to properly misconceptions scaffold these activities, including training students to No one identifies with student thinking or write questions and to critique their peers’ questions, we misconceptions better than the students themselves. think that the output is well worth the investment. Here Allocating students into groups provides them with a are ten reasons why. sounding board to test comprehension and exchange insights. Student-revealed misconceptions give 1. Large question pools address the increasing valuable intelligence for writing questions with strong demand for new exam questions distractors. Students become more effective learners The transition to online assessments marks the end of by reflecting on their own understanding, and we gain confidential exams, necessitating new exams every time insight into their learning processes to become more the course is offered. Additionally, students also often effective teachers. ask for practice questions, but with limited question banks, this is impractical. By leveraging the crowd, we 6. Questions are peer reviewed during development can very easily meet these demands (see Fig. 1). and before deployment Students reviewing their peers’ draft questions can be awarded marks to encourage thoughtful critique Fig. 1. A pool of and actionable feedback, and discourage platitudes 457 crowdsourced or unhelpful comments. Similarly, authors can be questions that awarded marks to edit their questions in response was used for to peer feedback. All of these activities promote early revision in 2019. and persistent engagement with course content, and develops students’ critical judgment and articulation 2. Individualised exams mitigate academic integrity skills. concerns The move to online exams has raised concerns about 7. Questions can be revised based on performance academic integrity, but with a large question bank, we metrics can more easily produce individualised exams to prevent Peer-reviewed, topic-specific questions that target collusion. A large, verified, crowdsourced question pool misconceptions sound great on paper, but quality is best can be categorised based on learning outcomes and judged by actual performance when deployed to the difficulty (see point 7). wider student cohort. We can use these performance metrics to take a targeted approach to fix any detected 3. Questions test understanding and are issues. One important caveat is that all questions must non-Googleable still be reviewed by an academic. For example, questions By introducing our students to Bloom’s Taxonomy, with no correct options can appear to be performing well they are encouraged to write questions that require if students gravitate towards the least incorrect answer. higher order thinking. This means that answers to their questions cannot be found online and rely on the students’ understanding and application of concepts.
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8. Student-authored questions are often original Reference and creative 1. Hancock D, Hare N, Denny P, Denyer G (2018) Students harness their own distinct perspectives Biochem Mol Biol Educ 46(4): 306–317. to design questions with fresh angles. The creative incorporation of analogies or references to pop culture Dr Alice Huang is a Casual Academic in the not only makes questions more fun to answer, but also School of Life and Environmental Sciences improves the resonance of often abstract concepts with (SOLES) at the University of Sydney. students. Even if some questions ultimately cannot be [email protected] used, the ideas can inspire new directions for us when developing our own questions. Professor Gareth Denyer is Professor of Biochemical Education in SOLES at the University of Sydney. 9. Students are empowered to shape their own [email protected] learning Asking students to write exam questions flips their Dr Matthew Clemson is a Lecturer in conventional role as passive recipients of information to Biochemistry, Cellular and Molecular Biology active interrogators. They are empowered to assess the in SOLES at the University of Sydney. relative importance of hierarchical levels of information, [email protected] from sweeping concepts to specific mechanistic details. The ultimate vindication of this opportunity to define Dr Giselle Yeo is an Academic Fellow their own learning, is manifested in the inclusion of their in SOLES at the University of Sydney. contributions in formal exams. [email protected]
10. Teamwork builds a dynamic resource that is greater than the sum of its parts The literature tells us that student engagement with PeerWise translates to a quantifiable improvement in exam performance (1). Individual lecturers in the course can take on different but complementary roles to facilitate a cohesive, consolidated resource for all course content. This platform informs how the course is received and interpreted in real time, allowing teachers to reflect and modify strategies to effectively support student learning.
Clockwise from top left: Giselle Yeo, Gareth Denyer, Matthew Clemson and Alice Huang.
Transitioning Case-based Biochemistry Workshops to Online During COVID-19 Melissa Sweeney1, Kathy Fernandez2 and Nirma Samarawickrema1 1Department of Biochemistry and Molecular Biology, Monash University 2School of Chemistry, Monash University
Teaching in 2020 has provided many unique Nutrition students undertaking a biochemistry unit, opportunities for educators to innovate and learn, following an interrupted case-study design (1) where particularly in the online learning space. We have spent students worked through a series of questions in small two years studying the implementation of biochemistry groups and then participated in larger class discussions case-based workshops, and teaching in the era of to consolidate the answers (Fig. 1). COVID-19 has allowed us to put our conclusions to the We developed a survey using the work from Harman test during synchronous, online workshops. et al. (2) as a guide and surveyed students on their In 2019, we facilitated workshops for second-year perceptions of the learning benefits of these classes.
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Students identified the structure of these workshops (including the interrupted case-study design with small and class group discussions and scaffolded worksheets), the real-world application of cases, support of the teaching staff and the peer-learning opportunities as the four major contributors to their learning (Fig. 2). We found it particularly striking that students found their peer-learning was enhanced in a teacher-led environment, and it seems that the scaffolding and tutor support allowed them to have meaningful, intellectual conversations with their peers, which greatly enhanced their understanding and retention of the biochemical concepts and the bigger picture context. Fig. 1. Structure of case-based workshops. When developing these workshops as online, synchronous classes in 2020, we aimed to deliver the same benefits. To adapt these, we used Zoom with the breakout room functionality to replicate small groups, while we maintained the worksheets, interrupted case- Melissa Sweeney is a study design and teaching staff who visited breakout PhD student and Teaching rooms and facilitated whole group discussions in the Associate in the Department main room. While we teach these classes in 2020, we of Biochemistry and Molecular are pleased to observe high levels of attendance and Biology, Monash University. participation, with students even staying back at the end [email protected] of class to continue the conversation. However, as most educators have found this year, the peer interaction aspect within the breakout rooms is a concern. As we begin to compile and analyse preliminary data from the 2020 cohort, we see that they still identify the structure of worksheets and small and large group discussions Katherine Fernandez is a and tutor support as benefiting their learningFig. ( 2). PhD student in the School of This tells us that our workshops can be effectively and Chemistry, Monash University. efficiently moved to an online, synchronous format in katherine.fernandez@ the era of COVID-19 and beyond, with one area for monash.edu improvement being student engagement. Our students have suggested that use of Zoom polls or Kahoots, and the ability to choose their own small group members would improve this. Facing the challenge of Dr Nirma Samarawickrema student engagement in the online learning environment is a Senior Lecturer in the will involve hearing the voices of our students (3), which Department of Biochemistry highlights the importance of these surveys. We hope and Molecular Biology, to use the results of our ongoing survey to make an Monash University. intentionally designed online learning experience for nirma.samarawickrema@ future students. monash.edu
References 1. Kulak V, Newton G (2014) Biochem Mol Biol Educ 42(6):457– 473. 2. Harman T, Fig. 2. Student identified learning benefits from 2019 face-to-face (F2F) (green) and 2020 online Bertrand B, synchronous (purple) case-based workshops. Order of rows reflect ranking. Greer A, et al. (2015) J Acad Nutr Diet 115(3):378–388. 3. Bovill C, Cook-Sather A, Felten P (2011) Int J Acad Dev 16(2):133–145.
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SDS Page: Short Discussions for Students Page
A Beginner’s Guide to Milestone Preparation Taylah Gaynor, Baker Heart and Diabetes Institute and Department of Physiology, Anatomy and Microbiology, La Trobe University
As the eventful year of 2020 continues, so do our Set a timeline and book meetings Masters/PhD timelines and the milestones they come Firstly, compare your own calendar and that of your with. The realisation of an approaching milestone can supervisor and find some dates that allow realistic cause a vast array of emotions, but a common feeling timeframes to achieve each goal. Book all meetings/ is nervousness, which often sets into panic as the date deadlines at the start of your preparations as this will approaches quickly. One moment you have six months give you a clear outline of how long you have for each until the milestone arrives, the next minute it is a month stage. By creating this timeline, you also ensure that away and it feels as though it has only been a week. your supervisor will be free when needed. By booking We begin searching frantically for ways to prepare for meetings in advance, it also keeps your supervisor on the milestones, asking colleagues for advice as we begin same page as you in terms of your expected outcomes to piece together a coherent story (particularly if it is and milestones. If you are unsure of how long you need your first milestone). Yet, what if there was a simple and between each stage, discuss this with your colleagues C effective way to plan and prepare for a milestone that or supervisor before booking. Be sure to book your M reduces stress and streamlines the process. Research Progress Panel Meeting for a time after you
Y With my confirmation fast approaching, I reached out complete your presentation. to my mentors and a few colleagues and asked for their CM recommendations on milestone preparation. I was able Create a skeleton and primary supervisor(s) review MY to gather a bundle of information that helped me piece Although this may seem like an obvious step to some, CY together an attack plan that enabled me to smash my it is a very clever way of setting expectations and saving
CMY milestone confidently and easily. time. By creating a very brief skeleton (first draft) of the presentation to bring to the first meeting with your primary K supervisor, you will be able to discuss how you imagine your project ‘story’ to flow. This meeting is not so much a rehearsal or practice but more of a chance to chat about the structure. This approach is far more effective, as it prevents you spending hours and hours on fine details only for the slides to be deleted later. Use this meeting to set clear expectations and intentions for the presentation so you can confidently get to work afterwards.
Lab presentation By now you should have a working second draft of your presentation that both you and your supervisor are, hopefully, happy with. It is now time to present to a larger group of people to gain some helpful and varied feedback. This will most likely be the first time you present your slides to a group, so take this time to write detailed notes on items that need to be added or things that require more practice, adjustment or removal. Be sure to follow the advice and feedback you agree with before the next meeting, so you don’t waste time readdressing items that were brought up in the past.
Supervisor and co-supervisors review Inviting co-supervisors to attend a rehearsal of your presentation can happen at an earlier point in preparation – this is up to personal preference. However,
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 25 SDS Page: Short Discussions for Students Page in this meeting, a polished third draft should ideally be progress paperwork has been submitted before any presented to bring your supervision panel up to speed. It deadlines. After following the above steps, you will is important to make sure all supervisors are happy with hopefully be feeling confident and well prepared for your your presentation so there are no surprises on the day. final presentation. Good luck! Additionally, it is helpful to have your progress report and other related paperwork prepared before this meeting.
Lab presentation A final presentation with the lab that is less about Taylah Gaynor is a PhD revision but more for practice. You can also organise candidate at the Baker Heart other practice presentations with friends and colleagues and Diabetes Institute and outside of your field of research to ensure your project is La Trobe University. clear. During this practice phase, make sure all required [email protected]
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PAGE 26 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 Competition: Campus Visit
Presenting the latest competition for the members of ASBMB. All correct entries received by the Editor ([email protected]) by 15 January 2021 will enter the draw to receive a voucher. With thanks to Joe Kaczmarski.
It has been a while since we’ve been able to visit each other in person at our amazing Australian research institutes and universities – can you recognise these buildings and campuses?
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Josh Ramsay (Curtin University), Tanima Dutta (Notre Dame University), Grishma Vadlamani (UWA) and Tara Richman (Harry Perkins Institute). A few months later, the day after the ASBMB 2019 meeting in Perth, the newly-formed PPG hosted Professor Sir Tom Blundell, Department of Biochemistry, University of Cambridge, who delivered an engaging and inspiring talk ‘Reflections on a Life in Science: Research, Travel, Entrepreneuring, Politics and Music; or on Being a Permanent Gap-Year Student’. Tom enjoyed a drink during a sundowner with the PPG members afterwards. PPG members flew the PPG banner interstate for the first time in February 2020, when about a dozen WA scientists attended the 45th Lorne Proteins conference, with Brady Johnston and Samuel Nonis taking student poster prizes home. PPG secretary Mark Agostino delivered a lightning talk entitled ‘Biophysical characterisation of Class F G protein-coupled receptor activation’. The Perth Protein Group (PPG) is one of ASBMB’s newest Special Interest Groups. The PPG was officially ratified by the ASBMB Executive on Monday 22 July 2019, days before our official launch on Friday 26 July 2019. The launch at the University of Western Australia (UWA) Watersports Complex was attended by 55 protein scientists from UWA, Curtin University, Murdoch University, Edith Cowan University and Notre Dame University, as well as from Harry Perkins Institute and Telethon Kids Institute biomedical institutes. The PPG Executive Committee consists of Josh Mylne (Chairperson and Webmaster), Abi Ghifari (Treasurer), Mark Agostino (Secretary), Nicolas Taylor (ASBMB Liaison), Brady Johnston (Media Officer) and three Events Officers, Jeffreena Miranda, Loreleï Masselot-- Joubert and Farley Kwok van der Giezen. We also have institute representatives: Pauline PPG social mixer held in Perth’s CBD. Zaenker (Edith Cowan University), Evan Ingley (Murdoch University), Clara Andradas (Telethon Kids Institute), In preparation for our AGM in 2020, we arranged a couple of great social mixers to get people talking. Our first social mixer was Friday 26 June at the Curtin Tavern. It was followed by a second on Friday 14 August at The Public House in the heart of Perth’s CBD. The first date set for our inaugural AGM was delayed due the global pandemic (how many times have we heard that phrase?), and eventually took place in scenic Albany on 4–6 September 2020 at the UWA Albany Centre, about a 5-hour drive south-west of Perth. We had 62 delegates make the trip ‘douth’. We adopted a similar format to the long-running successful East Coast Protein Meeting by starting late on the Friday afternoon and finishing around noon on the Sunday. The meeting was opened with a keynote by Associate Professor Archa Fox titled ‘Why I like paraspeckle Inspiring speaker Professor Sir Tom Blundell with PPG proteins’ on the first evening and Sunday’s proceedings Events Officers Jeffreena Miranda (left), Farley Kwok were opened by Professor Nigel Laing of the Harry van der Giezen and Loreleï Masselot--Joubert (right). Perkins Institute talking on ‘Why I like muscle proteins’.
PAGE 28 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 Perth Protein Group: an ASBMB Special Interest Group
Four winners were each awarded $150 a prize: • Best Student Talk – Aleshanee Paxman • Best EMCR Talk – Andrew Marshall • Proteomics International Poster Prize – Bence Olasz • ASBMB Poster Prize – Fraser Windsor Registration was a super-low $40 for the early birds and all reports so far indicate that everyone is looking forward to PPG 2021, which we might hold at Curtin University’s Margaret River campus. Our mission statement is to enable interaction and collaboration between protein research groups in Perth, create awareness of research strengths and key research equipment within Perth, raise awareness and extend membership of the ASBMB, create a forum for Attendees at the inaugural PPG AGM. students and ECRs to present their work in an informal atmosphere, help disseminate technical and practical Apart from our two keynote speakers, all other 23 talks aspects of protein science, and bring scientists from were by students and EMCRs with topics ranging from interstate or overseas to present their findings. structural biology, cell biology, proteomics, biochemistry and even some protein-centric bioinformatics. We also Josh Mylne, PPG Chairperson had a poster session with 19 presenters. In total, 62 Email [email protected] delegates registered for the meeting and PPG AGM Web perthproteins.org registration was accompanied by a rush on ASBMB Twitter @PerthProteins membership as we restricted speaker invitations to those with current ASBMB membership.
Metabolism and Molecular Medicine: an ASBMB Special Interest Group
The Metabolism and Molecular Medicine Special Interest and the topics covered included immuno-metabolism Group (MMM-SIG) is one of the largest in the ASBMB, and cancer, metabolic disease, lifestyle interventions and with more than 140 members. The goal of this group is to cancer, novel metabolic pathways in cancer, and cancer support activities that showcase the best research in this metabolism and therapeutics. Professor Grant McArthur field from Australia and abroad and provide opportunities from the Peter MacCallum Cancer Centre provided the for engagement for researchers who are members of the opening address for the meeting and the plenary lecture MMM-SIG. This has included organisation of symposia was delivered by one of the superstars of the cancer on topical areas of interest at ComBio meetings, as well metabolism field, Professor Ralph Deberardinis from UT as financial support for other conferences of relevance Southwestern Medical Center, who discussed his latest for members of the MMM-SIG. research on metabolic adaptations in lung cancer. In 2017, the MMM-SIG provided funding support for the MMM-SIG also supported the 6th AussieMit Meeting, second iteration of the Australian Cancer and Metabolism which was held at the Bio21 Institute in November 2018. Meeting, which was held at the Victorian Comprehensive This biennial meeting brings together a diverse group of Cancer Centre. This meeting brings together scientists researchers who study the role of mitochondria in health with expertise in nutrient metabolism, metabolic signalling and disease, and in addition to the primary scientific and cancer biology, with a goal to discuss the latest program, the meeting also had a dedicated ECR developments and advances in this rapidly expanding session and a patient day centred around mitochondrial field. There was excellent interaction between the more disease. The meeting was headlined by five international than 100 basic scientists and clinicians in attendance researchers: Professor Anu Suomalainen (Finland), Dr
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 29 Metabolism and Molecular Medicine: an ASBMB Special Interest Group
Cristina Ugalde (Spain), Professor Sir Doug Turnbull (UK), Professor Jared Rutter (USA) and Professor Peter Rehling (Germany), along with a number of eminent national speakers. The breadth of topics covered the role of mitochondria in metabolism, signalling, cell death and macromolecule biosynthesis, along with detailed investigations on processes that regulate mitochondrial function (protein import, respiratory complex assembly, etc) and a focus on mitochondrial disease. There were numerous highlights from the meeting including the superb opening plenary lecture by Professor Mike Ryan Above and left: (Monash University) on his elegant work dissecting Posters at mitochondrial respiratory Complex I assembly and the AussieMit 2018. opportunity to hear about the pioneering work of Professor Sir Doug Turnbull and his team on mitochondrial donation, an assisted reproductive technique that can prevent the transmission of specific forms of mitochondrial disease. Most recently, the MMM-SIG provided financial support for the Asia Pacific Diabetes and Obesity (APDO) meeting that was held as part of the broader Australasian Diabetes Congress in Sydney in 2019. The APDO group was founded in 2004 and the annual meeting of this group provides a forum that brings together a vibrant group of scientists in the Asia Pacific region who have a shared interest in diabetes and obesity. The 2019 meeting was the first time that the APDO group had convened a meeting in Australia and speakers were welcomed from Australia, China, Hong Kong, Korea, New Zealand, Singapore, Taiwan and Japan. The fantastic program included talks that spanned the spectrum from cutting edge fundamental science to clinical studies and there was lively discussions and interactions. The two plenary speakers were Professor Jake Lusis from UCLA and Professor Rob Yang from the University of NSW, with Jake providing a fascinating talk on the use of diverse inbred mouse strains to discover novel sex-specific differences in mitochondrial regulation, while Rob described his substantial body of work on lipid droplet biology and Above: Professor molecular regulation of adipogenesis. Overall, the 2019 Sir Doug Turnbull APDO meeting was a fantastic opportunity for Australian speaking at scientists to engage with our close neighbours, and the AussieMit 2018. success of this meeting will no doubt provide the impetus for the APDO group to hold future meetings in Australia. Given the ever-expanding recognition of the importance of metabolism in health and disease, the MMM-SIG is committed to supporting relevant activities in this field. With our limited resources, this support may not always be financial, however we can assist you to enhance the quality of your meeting by connecting you with the Right: Barefoot network of enthusiastic scientists within the MMM-SIG. bowls night at Please feel free to contact us if you have proposals AussieMit 2018. for future symposia at ASBMB meetings, or if we can support your research endeavours in some other way. Nigel Turner (Chair) and Sean McGee (Treasurer) Metabolism and Molecular Medicine SIG
PAGE 30 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 Off the Beaten Track
Written by former researchers who have now established careers outside of research, Off the Beaten Track is intended to give the readers insights into the range of alternative careers available to them. Authors describe the paths they have taken to arrive at their present career and provide a detailed description of exactly what the job entails on a day-to-day basis. Follow Your Dreams, Until Something Better Comes Along Mark Bleackley, Chief Scientific Officer, Incannex Ltd
and commercial research. Marilyn mentored me in how to manage multiple research interests and prioritise projects. I had feet in both camps throughout my time at La Trobe. I co-supervised Honours and PhD students with Marilyn and also worked with the Hexima team generating data for patents and dossiers for regulatory agencies. My focused shifted away from academia in my last 18 months at La Trobe. I had four unsuccessful applications for fellowships, three failed applications as co-investigator Mark for ARC and NHMRC grants and at least six unsuccessful Bleackley. applications for small grants. I was publishing, contributing to conferences/seminar series and supervising students, Until ten months ago, working in labs was the only real all the things you are supposed to do for a career in job I’d ever had. I started after my first year of undergrad academia, but for one reason or another my career doing endless plasmid preps and isolating proteins progression had stagnated. Fortunately, Hexima offered from animal organs, did a PhD using yeast genetics to me a role as project manager, which gave me the change understand how cells maintain metal homeostasis and a I needed to reinvigorate my career. In this role, I gained postdoc on antifungal peptides and fungal EVs. I did part- valuable experience on what it takes to get a drug ready time stints in fast food and pubs, but lab work was always for a clinical trial and the trial preparation itself. It was my main earner. My focus was pursuing an academic more complicated than I ever could have imagined, but career, the dream was always to run a lab of my own. I we learned as a team. was fortunate that during my time working in university- In October last year, I was contacted about a position based labs I was exposed to clinical and commercial as program manager at a new medicinal cannabis research, which prepared me for a career in industry. company, Incannex. I was interviewed and offered the Professor Ross MacGillivray, my PhD supervisor, had job in November. It was a hard decision to leave Hexima an excellent collaborative network with a group of clinical and the academic setting I had worked in for 20 years, haematologists. This opened my eyes to the different but it was an opportunity I could not pass up. I must have way studies are designed and implemented between impressed the management team at Incannex with my clinical and basic research. When I started with Ross, my research acumen as I was promoted to CSO shortly after direct supervisor was a PhD student named Mike Page. joining the company in January. Mike was always looking for new and different ways to Incannex’s focus is cannabinoid-based combination approach research questions and was always coming products to address unmet medical needs. We identified up with creative experimental designs. From Mike, I four therapeutic areas, obstructive sleep apnoea, learned about the benefits of taking time to understand traumatic brain injury, acute respiratory distress an experiment before you actually got the pipettes out. syndrome and temporomandibular joint disfunction. This is a habit that has been beneficial throughout my These were selected because of preclinical and/or research career. observational evidence that cannabinoids will have a I worked as a postdoc with Professor Marilyn Anderson therapeutic benefit. Our strategy is to identify other drugs at La Trobe University for eight years. Marilyn’s lab with history of safe use that will work in combination with was co-located with the biotech company Hexima Ltd, cannabinoids to create an effective treatment. We then where Marilyn is also a Chief Scientific Officer (CSO). assess the therapeutic efficacy of the drug combinations Working with Marilyn and Hexima allowed me to gain a in preclinical studies and placebo controlled randomised better understanding of the interface between academic clinical trials. One advantage of using combinations of
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 31 Off the Beaten Track previously registered drugs is that we are eligible for When I look back on how I developed the skills that I the FDA505(b)2 approval pathway that allows for some use as CSO at Incannex, there is no specific course or of the safety and stability data for the listed drugs to event that was pivotal. The most important skill I learned be used in regulatory applications. This is why I enjoy was how to ask the right questions. Examining student working at Incannex. We come up with creative solutions theses at an Honours, Masters and PhD level helped me to unmet medical needs and find the most efficient ways to develop this skill. to develop them to approved drugs. It is a fast-paced Working in academic departments exposed me to research environment, but it means progress is rapid. a variety to of research areas through departmental The work rate is intense at times, but it is worth it when seminar series and symposia that provided a plethora of we start to see results. knowledge seeds. There is so much information available Incannex is a very different working environment than at the click of a mouse these days, knowing where to start the universities I was used to. We are a small company, is half the battle. Countless times, an experiment I heard with four team members on the drug development side, about in a seminar on a topic completely unrelated to my a highly involved board of directors and supporting research made a valuable contribution to formulating a medical advisory board. There aren’t any lab benches, research plan. This is also what I miss the most about PCR machines or centrifuges. All of our preclinical work academic research. I’m no longer based in a building with is done by contract research organisations. This means hundreds of other scientists, many working on projects that we have to be very precise and sure about the way that are not related to what I do. This means I don’t get we design our experiments. Gone are the days when I to hear about the discoveries that are happening in an can ask a grad student to run some “suck it and see” academic environment. experiments to see if an idea has legs. All study designs When I was asked to write this article, one of the items are ratified based on the available literature and reviewed I was asked to cover was why I left research. I never did. by the research team. I just changed the type of research that I do. Early in my Clinical trial design is a major focus of our current career, we’d sit around at the pub on a Tuesday evening company activities. Each team member brings different and end up talking about how we’d run things when it experience and points of view to the table and our was our lab. It’s not where I ended up, but that’s because combined efforts lead to creative trial designs that something better came along. efficiently and effectively address our research questions. [email protected]
ASBMB Member Wins Western Australian Premier’s Science Award
ASBMB member Professor Ryan Lister from the University of Western Australia has received of the highest honour at the 2020 WA Premier’s Science Awards. Professor Lister was jointly named Scientist of the Year with astronomy researcher Professor Steven Tingay from Curtin University. Professor Lister is a genome biologist who has made major advances in our understanding of the epigenome, the molecular code superimposed upon the genome that can regulate the readout of the underlying genetic information. Through landmark technology developments and biological investigations, Professor Lister’s discoveries have provided new insights into the composition and function of the epigenome in diverse systems including plants, animals, human stem cells, embryo development, and the brain. His work is focused upon understanding how epigenome patterns are established and changed, how they affect the readout of the underlying information within the DNA sequence, their involvement in development and disease, and developing molecular tools to precisely edit the epigenome. Through this, his work is driving advances that will provide benefits to agriculture, human health and medicine. Professor Lister has also spearheaded the formation of Genomics WA, a new cutting-edge genomics research facility to serve scientists across Western Australia.
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VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 33 Timing is Everything: When to Pull the Trigger on Patent Filing
A series of regular articles How much data is enough? on intellectual property. In The development of a new therapeutic product is a long this issue, Sarah Hennebry, and complex journey. That journey typically begins with Patent Attorney, FPA Patent many years of basic research and hopefully culminates Attorneys, discusses the in the identification of a new molecule that is effective in timing of filing a patent. the treatment (or prevention) of a disease. While it is not always a requirement that a patent application have data, it is often the case that preliminary experiments contained in a patent application (whether in vitro or in vivo pre-clinical experiments), provide “plausibility” for patent claims which seek to carve out a broader monopoly. It would be an understatement to say that 2020 has For example, you may recall from an earlier article been a difficult year for researchers. However, time that I discussed “plausibility” in the context of a decision away from the lab bench has provided an opportunity for of the UK courts in relation to patent claims directed many to take a step back and think more broadly about to the use of the drug pregabalin to treat pain. The approaches for funding and collaboration. application contained data relating to use of pregabalin Unsurprisingly, the temporary separation from the in the treatment of inflammatory pain. This was deemed bench has seen many researchers reach out to sufficient to render it plausible that pregabalin could treat commercialisation teams at their universities/institutes to peripheral neuropathic pain, but not central neuropathic ask the question: do I have something that is patentable? pain. As such, the claims directed to treatment of any kind For many, the response is likely to be: probably… but not of neuropathic pain were deemed not to be supported by yet. This leads us to the question: when is the best time the specification. to pull the trigger on filing a patent application for your The amount of data contained in the patent application invention(s)? may be enough to get you some form of commercial protection – but it might not be enough to get you the Minimum requirements kind of broad claims that you have in mind. There can be many reasons for filing a patent application: to simply put a boundary around “background Be realistic – and plan IP” to facilitate discussions with a potential commercial When considering that first patent filing, it is important partner; to generate an asset that you can leverage to be realistic about the breadth of claim scope you can during negotiations with a potential licensee; building achieve with the data you have at that time. It is also upon an existing patent portfolio (which may be attractive important have in mind what experiments are planned to potential investors); and the more obvious reason: to for the coming months and years. Ultimately, what is be able to stop someone else from using your invention. required is a strategy that ensures that your earlier patent Whatever the reasons for filing a patent application, it is applications do not affect the validity of any applications generally desirable that the document can facilitate grant you may want to file in the future. This means that having of commercially useful claims defining a patent monopoly. narrowly-defined disclosures may be more appropriate In other words, there are only a few circumstances in than overly speculative disclosures. which a patent application would knowingly be filed at a For example, there may be value in confining the time and with information that is unlikely to lead to grant information in a first patent application to a more narrow of commercially useful claims. position, i.e. don’t overreach at this point and potentially In order for a patent to be granted, the claims need to damage the opportunity for subsequent or improvement define something (a product or a process) that is new, inventions which you may develop in due course. non-obvious (i.e., “inventive”) and has some sort of use. While your patent application might discuss certain Among other requirements, the patent application must variations to your lead compound, or alternative uses, if also contain sufficient information to enable someone of you don’t have the right data at the time of filing, you skill in the field to make or reproduce the invention. This might not be able to gain allowance of a patent claim that is usually where patent applicants run into trouble if a broadly covers the variation or broad uses. You might be patent application is filed too early. As such, the answer limited only to the specific example you have developed to the question as to when to file a patent application up to that point but in the meantime, have precluded often gets answered with another question: how much later opportunities for patent protection when you do data or experimental information do you have? eventually produce the variation.
PAGE 34 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 Timing is Everything: When to Pull the Trigger on Patent Filing
Imagine you have developed a new protein therapeutic Staggering applications and believe that this could be the first of a broader “class” A “staggered” patent filing strategy can be one approach of related proteins. You might define the class by a that enables you to keep your powder dry on downstream consensus sequence, but at this time you only have data uses/applications of your invention until you have the showing that one particular molecule is effective in cell data to support those uses. culture experiments. The impact of the earlier-filed applications can be Here, it will be important to consider whether your mitigated to some extent by timing the filing appropriately: commercial strategy is best served by withholding the first application will publish 18 months after filing, and information on the broader class of related proteins if you provided you or a third party have not made any other know you aren’t going to get data for any other examples publications in the intervening period since filing, the in the class in the next 12 months. It could be lethal to impact of the first filing can be minimised by ensuring that future prospects of obtaining claims to other members the second application is filed prior to that 18 month date. of this class if you put all that “speculative” information Of course, turning around the second or even further in your first patent filing, when you may only realistically applications within that time frame may not always be be able to obtain claims for the one protein you have possible. In that case, it would be necessary to point to exemplified. data or other evidence which indicate that even in the Of course, it is often the case that minor sequence knowledge of the information contained in your first variations to protein sequences are permitted in patent application, it would not be obvious to arrive at the later claims, but typically it helps if you have data showing invention. Such information can also include technical that the protein retains its activity (or would plausibly be reasons as to why the particular advantages or benefits considered to retain its activity) when minor variations/ of follow-on applications would not have been evident at modifications are made to the molecule. the time of the first filing. You may ultimately decide to wait to file the patent application until you can gather a bit more data which can be used to support “broader” claims to define the So what now? class of molecule. However, there may be competing There is rarely a situation when it is “too soon” to seek pressures to file a patent so you are able to publish the the advice of your patent attorney or commercialisation work you have now. This may mean that if you are ever team as to whether you have something that is going to seek patent protection, now is the time to file patentable. Remember to keep an open dialogue with something. As with many decision junctures in the world these partners and this will ensure that an appropriate of IP protection, often there will be a need to achieve a patent filing strategy can be developed early in the balance. Sometimes pulling the trigger early is the best pipeline, maximising your prospects of obtaining both option – but it is important to also be careful about the broad and narrow patent protection for your innovations. nature of the information included in that first filing.
Australian Society for Biochemistry and Molecular Biology Inc PUBLICATION SCHEDULE FOR AUSTRALIAN BIOCHEMIST, volume 52, 2021
Issue ASBMB Content Copy Deadline Issue Date
April 2021 52(1) Profiles of medal, award and fellowship winners Monday 8 February Monday 5 April Nominations for Executive/Council
August 2021 52(2) Nominations for medals, awards and fellowships Monday 7 June Monday 2 August Notice of AGM/proposed constitutional changes
December 2021 52(3) Annual reports Monday 4 October Monday 6 December FAOBMB/ASBMB conference report
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 35 NEW: Move It® adjustable tip spacing multichannel pipettes
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Compiled by Erinna Lee
Australian Capital Territory New South Wales Contributed by Matthew Johnson and Christina Spry Contributed by Kate Quinlan In December 2019, the International Nodes of Protein I am very happy to be able to report on the valuable Engineering Centre (INPEC) and Australasian Protein activities that NSW ASBMB has been able to support Engineering Meeting (APEM) Proteins Conference was in the last year. We helped to reward excellence in our held at the Australian National University. The ASBMB undergraduate biochemists and molecular biologists sponsored three student poster prizes at the meeting. at NSW universities. We funded the ASBMB Prize The winners were Jing Zhang (Leyton Laboratory, for Biomedical Science ($300) to the student with the Australian National University [ANU]), Vanessa best overall performance in all courses of the Bachelor Vongsouthi (Jackson Laboratory, ANU), and Mengqi Pan of Biomedical Science program at the University of (Kobe Laboratory, University of Queensland). Newcastle. Due to the restrictions placed on social gatherings this year, it was not possible to hold a prize giving ceremony, but I would like to congratulate Jonathan Taylor for being awarded this prize. We also supported the ASBMB Biochemistry Prize ($300) for Charles Sturt University, which was awarded to student Lucretia Quin. ASBMB NSW has been sponsoring the NSW Science Teachers Association Young Scientist Awards for several years and this continued in 2020. The ASBMB Award is given to the best high school student project with a biochemistry or molecular biology theme. Our involvement in schemes like this helps to encourage our future scientific stars and ignite their passion for research, which is particularly important during a year in which there have been limited outlets for high school students. ASBMB NSW has also partnered with a number of From left: Jing Zhang, Vanessa Vongsouthi, Mengqi Pan ASBMB Special Interest Groups this year to boost and Matthew Johnson at the INPEC-APEM conference. their ability to run events to support our members. We provided funding to the Yeast: Products and Discovery The National Biochemistry Lunchtime Seminar Series, (YPD) meeting in November 2019. We also funded coordinated by Thomas Huber (ANU), was initiated in the Thompson Prize, which is awarded for the best June in an effort to bring together biochemists based presentation by a young local scientist in the field of in Australia on Zoom during this challenging time. protein structure and function at the Sydney Protein The weekly series, which showcases the research of Group Thompson Prize Evening in November 2019. prominent biochemists located around the country, continues to run on Mondays at noon. To hear all about the exciting biochemistry research being undertaken, Queensland follow this link. The seminar program can be found here. Contributed by Ben Schulz and Michael Landsberg This year also brings a close to Matthew Johnson’s time Like many organisations, 2020 has been a disrupted as ACT State Representative. During his three-year term, year for the ASBMB QLD Branch with COVID-19 rules Matt established the Canberra Protein Group with ANU restricting the types and amount of activities that can take researcher Simon Williams, which supports biochemistry place. Nonetheless, ASBMB QLD remains steadfastly and structural biology in the ACT; and officially affiliated committed to supporting the promotion and development the group with the ASBMB as a Special Interest Group. of biochemistry and molecular biology at many levels The ACT will remain in capable hands as we welcome throughout the state. To this end, we have continued Christina Spry, who has been elected to take over the our sponsorship of undergraduate prizes for outstanding role of ACT State Representative. We are in the process achievement in biochemistry and molecular biology at of electing our first secretary to help support Christina Griffith University (awarded to Nicholas Hall) and James and our Special Interest Group. Cook University (awarded to Rebecca Bourquin and Ryley Dorney). ASBMB QLD also sponsored prizes at the Postgraduate Research Student Symposium hosted by The University of Queensland School of Chemistry and Molecular Biosciences. The annual Science Teachers Association of Queensland (STAQ) Queensland Science
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 37 News from the States
Competition was also sponsored by the branch, with prizes in secondary and primary student categories. An example of the The ASBMB QLD state branch has some exciting plans creative Oliphant moving forward into 2021, working in conjunction with Science Award the Queensland Protein Group, so stay tuned for more entries. details of these. Finally, we would like to acknowledge the service of Ben Schulz as the ASBMB Queensland State Representative for the past two years.
South Australia Contributed by Melissa Pitman Despite the upheaval of the COVID-19 situation this year, the SA branch of the ASBMB has maintained support for a range of activities. In my first year as the ASBMB SA State Representative, my aim was to learn Due to low COVID-19 cases in SA, the committee has the ropes and to increase awareness and membership of rallied under the steady guidance of Chairperson, Erin the ASBMB in the state. Mark Corbett has been a wealth Brazel, to run a local event to bring together people to of knowledge and has helped ease the transition and participate in the ASBMB Research Symposium and all flattened the learning curve. going well, the APG will run its annual networking event, Each year, the SA branch of the ASBMB supports a Proteins in the Pub, in December. range of events from high school level to undergraduate, The Oliphant Science Awards, run by the South postgraduate and beyond. With the restrictions brought Australian Science Teachers Association for students about by COVID-19 in 2020, event planners have had from reception to year 12, successfully moved to an to be creative by moving to online formats and delay online format this year. It is very inspiring to see the events in order to forge ahead. This has brought about a innovation and creativity of the students in their discovery change in routine with the timing of some sponsorships of STEM. This year, the ASBMB prize was judged by and events. Rhys Hamon (Centre for Cancer Biology and University Last year, the ASBMB sponsored an ECR poster of South Australia) and was awarded to a Year 7–8 award at the Barossa Cell Signalling in Cancer Medicine student, Sienna Hill, with her scientific enquiry ‘Starch conference (12–15 November 2019), which was awarded hydrolysis by amylase and detergent’. to Helen Palethorpe for her work on microRNA in cancer The Centre for Cancer Biology and University of and a student poster prize at the 8th Cell Architecture South Australia ran a small, socially-distanced event to in Development and Disease symposium, which is a celebrate PhD student and ECR excellence. The ASBMB satellite meeting of the Australian Neuroscience Society contributed towards two prizes: best prizes were awarded Conference. In October 2019, the APG was invited to run to Naranie Shanmuganathan for her work on molecular a symposium at the ASBMB conference in Fremantle, monitoring of CML patients (published in Blood) and WA. This was a wonderful opportunity to showcase the Heidi Neubauer for her work on regulation of cytoplasmic work of our SA researchers. dynein in glioblastoma (published in Oncogene). The University of Adelaide runs an annual award for second year undergraduate students in the Biological Sciences discipline, supported in part by the ASBMB SA branch. This year, the prize was awarded to Alison Roennfeld and she will receive the prize at an upcoming ceremony. This year, the SA branch will also sponsor the Cochlear Aurora STEM Photo contest, which is currently still open for submissions. I hope to update you and include the winning image in the next report. ASBMB ECR poster prize At the beginning of 2020, I contacted ASBMB SA winner Helen Palethorpe members to remind members that student memberships (left) with SA State were free for the first year and to encourage their Honours Representative Melissa and PhD students to join our Society. This is something Pitman at the Barossa that I plan to do twice a year with the hope that it sustains Cell Signalling in Cancer and increases membership numbers. At each APG Medicine Conference. event, I get the opportunity to spruik the ASBMB and promote the benefits of being part of a national society of
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term as the Victorian State Representative has now come to an end and we welcome Laura Osellame (La Trobe Institute for Molecular Science), who will be taking over the role and who will be a wonderful representative for all our Victorian ASBMB members.
Western Australia Contributed by Monika Murcha The Perth Protein Group (PPG), led by Joshua Mylne (School of Molecular Sciences, University of Western Australia [UWA]), held their inaugural 2020 Melissa Pitman (centre) at the Centre for Cancer AGM on 4–6 September at the UWA Albany campus. Biology and University of South Australia PhD student A total of 61 registrants were fortunate enough to get and ECR excellence awards with prize winners Naranie away to WA’s beautiful south and listen to two plenary Shanmuganathan (left) and Melinda Tea (right) on lectures given by Archa Fox (UWA) and Nigel Liang behalf of Heidi Neubauer. (Harry Perkins Institute). In addition, 23 early and mid- career students and researchers were also invited to scientists and educators with a passion for biochemistry present their research in the form of oral presentations. and molecular biology. I always encourage attendees to This provided a great opportunity for many of our WA tick the SIG boxes when they renew their membership members to present at a face-to-face meeting given the and to stay engaged and involved with the local events. current interstate and international travel restrictions. I have also reminded all members of the APG committee The ASBMB WA branch sponsored a prize for the to make sure their membership is up-to-date and emailed best student poster presentation ($150), which was gentle reminders to current ASBMB members and lapsed awarded to Fraser Windsor, an Honours student from the members to keep them informed of local developments School of Molecular Sciences, UWA. As a result of this so they don’t miss out. meeting (and regular PPG Friday afternoon sundowner I wanted to finish by noting that while this year has meetings), we have seen a substantial increase to our been difficult for scientists and science alike, I have been WA membership. blown away by the energy and adaptability of educators and researchers. I have been inspired by the speed and creativity of the shift to online teaching, communication and conferencing. While we all hope that things will go back to normal, I think some of the positive innovations and changes in structure caused by COVID will be here to stay. Fraser Windsor, an Honours student from Victoria the lab of Yit Heng Contributed by Erinna Lee and Laura Osellame Chooi (School of The ASBMB VIC branch continues its commitment Molecular Sciences, towards supporting a diverse range of activities within UWA), was awarded the state. All sponsored events share the common the ASBMB WA- goal of promoting the communication and development sponsored poster prize of science, in particular the field of biochemistry and at the inaugural Perth molecular biology, amongst both established and future Protein Group AGM. scientists. Unfortunately, due to the COVID-19 pandemic and Once again, the ASBMB WA branch supported the Victoria enduring one of the longest and strictest Combined Biological Sciences Meeting (CBSM), an lockdowns in the world, many activities have had to be annual meeting formed and run by undergraduate cancelled or placed on hold. The only event sponsored by students to promote biological science in Western the ASBMB VIC branch in 2020 was the Science Talent Australia by encouraging the interaction of scientists, Search. This popular annual event for aspiring young students, and industry from all of the life sciences. scientists moved to an online format with student projects The conference was held on 27 November 2020 at submitted and evaluated using an online platform. the University Club, UWA, comprised predominantly of Finally, Erinna’s (La Trobe Institute for Molecular student and early career speakers. ASBMB WA again Science / Olivia Newton-John Cancer Research Institute) sponsored the student poster prize ($300).
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 39 You can rely on us for the quality of our products and our service,
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PAGE 40 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 206 / 354 Eastern Valley Way Chatswood NSW 2067 Australia Great Expectations
It’s Not Only What You Know, It’s Who You Know – an Unplanned Career Paul Attwood
As I near retirement and look back on my career, Formative years it seems to me that chance played a major part in the I grew up in Ilkeston, a small iron and steel/coal mining directions in which it took me. I have tried to summarise town in the East Midlands of England, between Derby this in the figure which shows that a couple of key points and Nottingham. I was educated at Ilkeston Grammar my career path might have been quite different had I School where I had an excellent Chemistry teacher, Mr made other choices. It also illustrates the importance Kerr, who also started me off on my life-long interest of personal connections throughout my career or as my in classical music. In the sixth form, I studied Maths, mother used to say, “it’s not what you know, it’s who you Physics, Chemistry and General Studies. I was very good know”. at Chemistry, but I thought there would be more career opportunities if I studied Biochemistry at university (note in those days not having studied biology at A-level was not considered an impediment to taking a degree in Biochemistry). Having applied for places at five universities, including Birmingham, I went, as was usual in those days, to interviews at four of them and was accepted at my first choice of Bristol University. I was the first member of my family to attend university. At that time, Biochemistry at Bristol was considered to be almost on par with Oxbridge and was home to Brian Chappell, the eminent mitochondrial biologist, the X-ray crystallographers Herman Watson and Hilary Muirhead in the Protein Crystallography Lab, and the physical biochemists and enzymologists, Freddie Gutfreund and David Trentham in the Molecular Enzymology Lab.
Bristol The first year of my BSc (1976) comprised Maths, Chemistry and Biochemistry, the second year was Chemistry and Biochemistry and the third year was just Biochemistry, with research projects embedded, leading to an Honours degree in Biochemistry. At that point, it seemed to me that having spent a lot of time developing friendships in Bristol and getting to know 121 pubs, that it wouldn’t be a bad idea to spend another three years there doing a PhD. But who to do it with and on what? Since I was reasonably good at maths and chemistry and having understood and enjoyed Freddie’s lectures in enzymology, I thought that I might do well in his lab. So I embarked on a project to try and understand the mechanism of the pigment rhodopsin in its role in visual transduction. This involved many trips to the abattoir collecting cows’ eyes and hours spent in cold rooms, in dim red light, dissecting the eyes and removing the retinas to prepare rod outer segments and discs. After much assistance from Freddie, Mike Geeves and a
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after paper and this sociability that made the experience unforgettable. As a bonus, the people in Janet’s lab were also gregarious and between the two labs, we made a number of life-long friends. However, all good things must come to an end and after three years I started to think about my next move. As it happened, in conjunction with the IUBMB meeting in Perth in 1982, a satellite meeting on biotin-dependent enzymes was organised by John and Bruce in Adelaide. I was delegated to pick up Mo Cleland and his family from the airport and so met my future postdoc supervisor for the first time. I wrote to Mo to ask him if I could have a postdoc position in his lab in the Department of Biochemistry at the University of Wisconsin–Madison. I must have made a good impression on him in Adelaide, as he agreed to take me on. Members of the Molecular Enzymology Laboratory at the University of Bristol in 1977. couple of EMBO fellowships to work in Benno Hess’ lab in the Max Planck Institut fur Ernahrungsphysiologie in Dortmund, I managed to publish my first paper. This was in FEBS Letters describing the application of pressure- relaxation kinetics to the investigation of the equilibrium between metarhodopsin I and metarhodopsin II that is crucial to the initiation of the visual process. I successfully defended my thesis at the required viva towards the end of 1980. I also meet my wife, Janet, in this period in the Molecular Enzymology Laboratory. As I was writing up my thesis, it occurred to me that I Members of John Wallace’s laboratory at the University would need a job after my PhD. I applied to the Forensic of Adelaide circa 1982. Paul is on the left and John is Science Service and was offered a job at the newly on the right. opened labs in Chepstow. However, during this period, John Wallace from the University of Adelaide visited Madison the lab and I helped him with some measurements on Madison is very different from Adelaide, being in the a photon-counting fluorometer. It became apparent that mid-west of the USA, 150 miles northwest of Chicago John was a keen oenophile who was also not averse and about 50 miles west of Milwaukee. It is hot and sultry to beer/cider drinking, so one evening I took him on a in the summer and can be freezing cold in the winter. lengthy pub crawl of Clifton, the Georgian part of Bristol One day in the second winter I was there (1985) it got to where the famous Brunel Suspension Bridge is and -33ºC, with the wind chill this was estimated to correspond also the infamous cider pub, the Coronation Tap. Just to -86ºC. Winter sports include ice fishing on the frozen before I was about to accept the position in Chepstow, lakes that surround the city (I did not try this) and cross- an offer of a Senior Teaching Fellowship in the laboratory country skiing, which was great fun and is the best use of John Wallace and Bruce Keech in the Department for golf courses in my opinion. Another great attraction of of Biochemistry arrived. What to do? The lure of travel, life in Madison was that it was in the US state most noted plus Janet’s agreement to go led us to Adelaide and to for its breweries and beer (no Budweiser was drunk in my embark on one of the best periods in my life. time there). In the lab I worked on pyruvate carboxylase again, with a main focus on determining 13C and 2H kinetic Adelaide isotope effects on the enzyme-catalysed reaction to try As a young postdoc with no mortgage, no children and understand how the carboxyl group is transferred and quite a good salary, in a sunny city near the sea, between biotin and pyruvate. These experiments were virtually surrounded by vineyards and home to the very satisfying as they gave quite definitive results, Coopers Brewery, it was fantastic. Bruce and John’s lab however they were very long experiments. They would was extremely sociable and from memory, the day after start in the morning with the preparation and degassing we arrived we went on our first winery tour. However, it of reaction solutions, then running the reactions in sealed was the combination of exploring the kinetics, structure flasks in the afternoon and evening. Then fractionally and function of pyruvate carboxylase, publishing paper distilling the carbon dioxide produced in the reactions
PAGE 42 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 Great Expectations
overnight and finally doing the isotope ratio mass in the treatment of bipolar spectrometry measurements the following day. As in disorder and managed to Adelaide, the members of my lab and also my wife’s lab obtain some idea of the were very sociable and again, according to my mother it substrate specificities of the is fine to play hard if you work hard. Working in the USA enzyme by collaborating felt like being close to the centre of my field of research with the in-house chemists (enzymology) and in the photograph taken at the annual who made some substrate/ Gordon Research Conference on Enzymes, Coenzymes inhibitor molecules for me and Metabolic Pathways in 1985 are gathered many of to test. This is another the greatest names in the field including Mo himself, Bill advantage of working in Jencks, Harland Wood, Vern Schramm, Jeremy Knowles a private institute like the and many others. Merrell-Dow, with a range of disciplines immediately available in-house, e.g. X-ray crystallography, NMR, animal physiology and psychology. A disadvantage of working in this sort of company-based institute is that commercial takeovers are not that uncommon, but which I found quite unsettling, when it looked like happening to us. This was one reason why I jumped at the opportunity to apply for a lectureship at the University of Western Australia in 1987.
Perth One day in my office in Strasbourg I received a telephone call from Australia. If I remember correctly it was Mike Guppy from Biochemistry at the University of Western Australia, he simply said, “are you still interested in the position?”. I said yes and that was the extent of the appointment process. Today of course this could not Attendees at the Gordon Research Conference on happen, but having John Wallace and Bruce Keech as Enzymes, Coenzymes and metabolic pathways in 1985. my referees was decisive at that time. 1 Mo Cleland, 2 Bill Jencks, 3 Harland Wood, 4 Vern The last 32 and half years at UWA have on the whole Scramm, 5 Jeremy Knowles and 6 Paul Attwood. been interesting and pleasant, I finally got a mortgage, we had a daughter and we have made some very close Strasbourg friends. Of course, funding being what it is, my research Towards the end of 1985, I had to decide what to do next. If I left the USA prior to two years stay, I would not have to pay income tax, so I applied for a couple of jobs, one of which was in the Merrell-Dow Research Institute in Strasbourg, France. I was asked to apply for a job at Oxford University, but since I had already accepted the position in Strasbourg, I declined to do so. The sojourn in Strasbourg was interesting in a couple of ways, firstly it is the only time I have worked in private industry, which meant being paid well, having excellent laboratory assistants, having a large budget but also having some constraints on what I could work on. Secondly, although both Janet and I spoke reasonably good French, being in Alsace and on the border with Germany, sometimes other Paul with the first languages and dialect were mixed with the French. This mass spectrometer aside, we had a good time in Strasbourg and enjoyed (QSTAR®) devoted walking in the Vosges, the wine villages not far from the to protein analysis city, cross country skiing in the Black Forest and making at the University of friends, with whom we are still in contact. I worked mainly Western Australia. on myo-inositol-1-phosphatase, the putative target for Li+
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structure of pyruvate carboxylase and fully define its mechanism. This we did and ultimately, were funded by NIH for eight years. We determined the first structure of pyruvate carboxylase (done mainly by Martin St. Maurice and Ivan Rayment in Madison), as well as define its mechanism. As it happened, this work also uncovered many unexpected aspects of how the enzyme functions as a tetramer, i.e. inter-subunit catalysis and half-of- the sites-activity. One outcome of the NIH collaboration was the involvement of Sarawut (Yui) Jitrapakdee who is now a Professor at Mahidol University in Bangkok, but who was a PhD student of John Wallace. When the Paul at the UWA Staff Club with Jialing Bao (right), NIH funding finished, shortly followed by Mo’s untimely a visiting teacher from Southwest University in death, Yui and I continued a collaboration that has seen Chongqing, China, and part of the newly instigated five of his students spend time in my lab learning enzyme teaching program. This led to Paul making eight kinetics and has enabled me to visit Thailand a number teaching visits to China in 2017–2019. of times. More recently, we were successful in obtaining a grant from the Thailand Research Fund to investigate has not always been easy. I want to make two last the role of biotin enzymes in cancer. observations on the central theme of this article with Since I am now retiring, when I look back over my career, respect to research funding. For the first years at UWA, it is more the people I have known that I remember rather I continued my work on the mechanism of pyruvate than the papers I have published or the grants I have carboxylase, but it became more and more difficult to obtained. obtain funding for this research. One approach to this dilemma that I took was to develop a new area of research – mammalian protein histidine phosphorylation. But how to get funding in an area that I had no experience? I asked Philip Cohen, one of the greatest researchers in protein phosphorylation, if I could spend a short sabbatical in is lab, working on anything he chose, but to get experience in the techniques of protein phosphorylation. I spent eight weeks in his lab in Dundee and managed to get some results that led to a publication in EMBO Journal. Secondly, I took another short sabbatical in Christoph Turck’s lab in San Francisco, working on histone H4 histidine phosphorylation using mass spectrometry. It worked, I got an ARC grant in collaboration with George Yeoh and Marie Bogoyevitch, both from UWA. The second approach to the funding problem was to collaborate with John Wallace and ask Mo Cleland and apply for NIH funding for a program to determine the Banking shouldn’t be rocket science. Managing your finances can be daunting, but it doesn’t need to be. Talk to one of our team today and we’ll set you on the right trajectory.
Martha Ludwig, Head of the School of Molecular Sciences, University of Western Australia, speaks at Paul’s retirement function in July 2020. PAGEPhoto 44 credit: Josh Mylne and Victoria Cornford.AUSTRALIAN BIOCHEMIST lcu.com.auVOL | 9518 NO59 3 0 DECEMBER585 2020 ASBMB Member Named Melburnian of the Year
ASBMB member Professor Doug Hilton has been named 2020 Melburnian of the Year for his leadership in the medical research sector and contribution to the Melbourne community. The award is the City of Melbourne’s highest accolade. The 2020 Melbourne Awards recognise people who had demonstrated acts of kindness, integrity and community spirit during the COVID-19 pandemic. Doug Hilton grew up and went to school and university in Melbourne. He has been a medical researcher at the Walter and Eliza Hall Instistute (WEHI) for 35 years and its Director since 2009. Professor Hilton said he was humbled to receive the award, which he said was a reflection of the entire WEHI team and the scientific community more broadly. “WEHI was Melbourne’s first medical research institute and, in the 105 years since it was established, has continued to play a vital role in responding to community need. I’m proud to see how our researchers have rallied together, not only within WEHI but also with our partners around Melbourne and Australia, to respond to this public health challenge. We are working more collaboratively than ever before and with an incredible generosity of spirit to deliver benefit to the community. “This year has challenged us in every respect. The staff and students at WEHI have been fantastic throughout the process and I’m incredibly proud to lead an organisation filled with such amazing people. We have research teams working to understand the biology of the virus and the immune response to the virus, to test existing therapies and develop new therapies to fight this novel virus. This work will help us combat not only this pandemic but other pandemics that may arise in the future. As someone who has spent most of my life living and working in Melbourne, I’m really proud of how we have gotten through such a difficult period and how we have supported one another during this time.” WEHI researchers have discovered a chemical combination which can block the coronavirus protein PLpro. PLpro plays essential roles in viral replication and evasion of the host immune response. WEHI is also leading a trial of hydroxychloroquine in healthcare workers as a preventative measure against COVID-19 infection.
In Memoriam
Ian Parsons 1926–2020 Ian Parsons was a real son of Melbourne, born campus was established in Balwyn in December 1926. He spent a long and on a converted RAAF productive life before he passed away in July 2020, base in the North-West of aged 93 years. He lived for 66 years in his family home Victoria with the intention of in Sandringham, a Bayside suburb that played a huge providing tertiary education role in his life. He was one of the earliest members of for servicemen and women the Australian Biochemical Society from 1954 (only 14 recently returned from the members are recorded for that year, the first year of the Second World War. The Society’s activities); he retained membership until 2017. plan to establish a separate He was Editor of the ABS Newsletter in 1972 and 1973. university at that location Ian enrolled in a BSc degree at the University of was abandoned when Melbourne in 1944 and completed his degree in 1946, enrolments declined greatly Ian on a cruise of the majoring in Chemistry with an interest in the relatively in 1949 and the Mildura Inside Passage of Alaska new field of Biochemistry. Ian’s first job was a Tutor in Branch was closed. Ian with his family in 2018. Chemistry at the newly opened Mildura Branch of the returned to Melbourne where Photo: Mike Parsons. University of Melbourne. This rough and ready rural he enrolled for an MSc
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 45 In Memoriam degree under the supervision of Bill Rawlinson in the hormones and morphine in blood, and quantification Department of Biochemistry. He graduated in 1951, of vitamin B12 and folate. Later, measurements of with his thesis entitled ‘The relation of metal ions to the glycosylated haemoglobins (such as Hba1c) using biochemistry of yeast and bacteria’. This introduction column chromatography kits were established under to the biochemistry of enzymes, metalloproteins, Ian’s careful supervision; he often carried out these porphyrins and cytochromes underpinned Ian’s later measurements himself. This clinical biochemistry contributions to clinical biochemistry especially in the enterprise closed after ten years, coinciding with Ian’s areas of blood biochemistry and cancer. retirement in 1988. Ian was employed for eight years from 1953 as a Ian was a popular and effective teacher over his career Staff Biochemist at the Peter MacCallum Clinic and at Monash, with great concern for student welfare. He the associated Cancer Institute (as it was known at was a likeable and gregarious person who maintained the time). During this period, he published a series of his relationship with many staff members long after he papers in collaboration with clinicians, on various topics retired. He was one of the kindest academics we have in medical biochemistry. These included porphyria, ever met, a real gentleman. blood enzyme deficiencies in Papuan populations, He enjoyed his retirement for the next three decades, studies on neoplastic growth and an interesting study continuing his interests in meteorology and yachting. of the efficacy of sunscreen components in lipstick! This He had his own weather station in his Sandringham period established Ian as a clinical biochemist and he home, and he built at least two yachts which he sailed was one of the earliest members of the Australasian in association with local sailing clubs, particularly Association of Clinical Biochemists (founded in 1961), those at Black Rock and Hampton. He was a naturalist of which he remained a member for 40 years. and enjoyed the outdoors both locally and overseas, The Department of Biochemistry at Monash University photographing the wildlife. Ian was a family man, was founded in 1961 under the Headship of Joe devoted to his wife Alison who passed away in 2003, Bornstein, with responsibilities for teaching in the MBBS after 53 years of marriage. He leaves a daughter degree at that newly established university. Ian was Heather and a son Jim (who kindly gave the authors appointed Lecturer in Biochemistry, and he participated many details about Ian’s life), five grandchildren and in teaching medical students for almost the next 30 years three great-grandchildren. until his retirement in 1988. Ian continued his research Phillip Nagley and Clem Robinson and enrolled for his PhD at Monash (as Staff Candidate) under the supervision of Bornstein. He graduated from his PhD in 1967, with his thesis entitled ‘Aspects of the metabolism of mammary tumours and their interaction with testosterone’. Ian published a single author paper in Nature on his PhD research! Ian spent a Sabbatical leave during 1966–1967 at the Marie Curie Institute in Oxted, Surrey, UK, where he worked on testosterone and the rat prostate. Promoted to Senior Lecturer at Monash in 1966, Ian focussed on teaching medical and science students for the next two decades. Ian’s technical expertise in many aspects of clinical biochemistry came to the fore once more in the late 1970s when Joe Bornstein and Tony Linnane (in conjunction with pathologists) established a pathology laboratory service within the Department of Biochemistry in order to generate income for the department at a time of severe financial stringencies in university funding. Dr Ian Parsons (left) and Professor Tony Linnane with The company Microclinical Chemistry was set up with a liquid scintillation analyser used in blood morphine Ian as laboratory supervisor to carry out specialised measurements. Reprinted with permission from the assays that were then not routine in standard pathology Monash Review (March 1978, published by Monash labs. These included radioimmunoassays for various University). Photo: Herve Alleaume.
PAGE 46 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 ASBMB Annual Reports
President’s Report
This has obviously been an unusual year for the Society and for all of its members, and I very much hope that people have made it safely to this point – it is certainly encouraging to see the situation in Victoria improving substantially at the time of writing. It looks like Australia ASBMB has manoeuvred itself into an enviable position with President regard to COVID-19. Let’s hope that success translates Joel to a higher profile for science at a national level. Mackay.
Meetings 2020: Since the last Council meeting, ComBio2020 has been postponed until 2022 (September 27–30) – keeping is also important that we consider the appropriateness of the same organising team and same location (Melbourne SIGs and their relevance to the Society membership in Convention Centre). Thanks very much to Jackie Wilce an ongoing way. and Mark Hulett – and Sally Jay – for agreeing to stay on as the team for the postponed meeting. ASBMB Award Recipients A decision was taken to hold two back-to-back online I would like to take the opportunity to congratulate our ASBMB meetings on September 29 and 30 this year, as 2020 award recipients: a way to provide an opportunity for members to connect The Lemberg Medal with each other – and also, importantly, to allow us to Trevor Lithgow (Monash University) acknowledge the ASBMB award winners for 2020. One The Shimadzu Research Medal meeting was focused on talks from the award winners Colin Jackson (Australian National University) (and their award presentations), whereas the other The SDR Scientific Education Award meeting was education focused. The two meetings Nirma Samarawickrema (Monash University) were enthusiastically and capably organised by ASBMB The Eppendorf Edman ECR Award members – led by Tatiana Soares da Costa and Nirma Si Ming Man (Australian National University) Samarawickrema, respectively. There were more than The Boomerang Award 200 registrations for both meetings – which I think is Matthew Doyle (National Institutes of Health, USA) fantastic and to my eye a strong indication that education ASBMB Fellowships should step up to be a bigger area of focus for ASBMB. Amy Baxter (La Trobe University) – Fred Collins Award It is perhaps something that ties members together even Steffi Cheung (University of Melbourne) more closely than our research interests – which I think it Mengjie Hu (University of Melbourne) is fair to say are more diverse. Anukriti Mathur (Australian National University) 2021: The FAOBMB Congress is still going ahead in Christchurch and ASBMB are committed as co-hosts for Running the Society that meeting. We have also decided to run an expanded I would like to thank the current and recent members of East Coat Protein Meeting as an Australia-based meeting the ASBMB Council for the time and effort they have put in 2021. This will be co-hosted by all of the Protein Groups into the Society. These are purely voluntary roles and I that are SIGs of ASBMB and led by the Sydney Protein am very grateful that they give up their time to serve the Group under the leadership of Tara Christie. biochemistry and molecular biology community. Without 2022: We will be in Melbourne, as noted above. the efforts of such people, the Society would cease to 2023: We are hopeful that an ASBMB-focussed meeting exist. Briony Forbes (and Dominic Ng in transition as will be run in Canberra, led by Colin Jackson. This has newly elected Secretary) and Marc Kvansakul have not been firmed up yet. done a lot of work behind the scenes to keep the Society 2024: The IUBMB Congress in Melbourne is being functioning. Tatiana Soares da Costa is continuing to planned by a team led by Leann Tilley. increase the effort she puts into ASBMB, adding STA Biological Sciences representative and FAOBMB 2021 Special Interest Groups (SIGs) International Committee membership to her portfolio. Over the last few months, we have had discussions Also, supporting the efforts of the Council are Sally and about reemphasising the role of the Special Interest Chris Jay and the National Office – without whom we Groups as advocates of ASBMB and we have sent out a would be in big trouble. They are an enormously valuable message to them to lay out their responsibilities, hopefully resource for the Society. Thanks to the ASBMB Editorial encouraging a closer connection between the SIGs and Officer and Webmaster, Liana Friedman, for her ongoing the Society – and also between the SIGs themselves. It diligent work for the Society.
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 47 ASBMB Annual Reports
Jacqui Matthews is now in the President Elect role into the ComBio2020/2022 meeting. Initiated the and will take over the Presidency in 2021. Dominic Ng ASBMB Education-focused meeting for September will likewise take over the Secretary role (and has been this year. Encouraged the Education SIG to think warming up this year already in that position!) and I about organising more standalone events for their welcome them both and thank them for their commitment to membership]. the Society. Matthew Johnson, Kate Brettingham-Moore, • Providing better guidance and support for State Ben Schulz, Kate Quinlan and Erinna Lee will step down Representatives in their roles and considering the as Council members and are being replaced by Christina introduction of a formal network of institutional Spry (Australian Capital Territory), Laura Sharpe (New representatives to provide deeper engagement in South Wales), Michael Landsberg (Queensland), Iman individual institutions. [Established regular meetings Azimi (Tasmania) and Laura Osellame (Victoria). of the State Representatives to encourage discussion among them and sharing of their experience Other Initiatives and activities. Tidied up the guidelines for State As I have outlined previously, there are several initiatives Representatives. Sought and obtained input from State I was hoping to pursue in 2020. These are below, along Representatives on how they felt they could be better with what action has been taken. supported in their roles by ASBMB. Appointed a ‘Lead • Considering the re-establishment of an ASBMB- State Representative’ – Erinna Lee – to coordinate led annual Heads of School/Discipline meeting as a meetings between the State Representatives]. forum for the exchange of ideas amongst discipline • Surveying members (and hopefully lapsed members leaders within Australia. [No progress on this item – and even non-members) to find out what they think but I am still committed to trying this before the end of the ASBMB could and should play for them. [No 2020]. progress on this item to date]. • Strengthening the focus on Biochemistry Education Professor Joel Mackay, President within the Society. [Introduced an Education Plenary [email protected]
PAGE 48 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 ASBMB Annual Reports
Treasurer’s Report
Relevant summaries of the full audited report (1 July 2019 to 30 June 2020) should be read in conjunction with ASBMB this statement. Final audit has been subject to COVID-19 Treasurer delays, and the summary statements on which the report Marc is based were provided by our auditors. Full financial Kvansakul. outcomes for the 2019–2020 financial year will be published in the April 2021 issue. The overall position of the Society has substantially deteriorated compared to 2019–2020. We recorded an operating loss of $66,473 compared to a profit of $45,455 With the postponement of ComBio2020 to 2022, we will in 2018–2019. This year’s outcome is largely due to the face an additional 18 months until any significant income loss from ASBMB 2019 (-$52,014) compared to the profit will materialise from sponsorship for ComBio2022. Whilst made at ComBio2018 ($60,664). Consequently, revenue a stand-alone ASBMB meeting is being planned, it is dropped by $112,678. Clearly the mode and format of unlikely to return a significant profit, and consequently ASBMB stand-alone conferences require some thought I believe it is inevitable that we will need to access our going into the future. cash reserves again. In addition, due to the use of cash The major sources of income for ASBMB are membership reserves, our income from bank interest will also be revenue, ComBio profits and bank interests. Advertising reduced. Realistically, we are only continuing to support income was $4,280, a small increase compared to the Society activities due to our reserves, and will likely need previous year. Corporate support for our named awards to innovate again to reduce our cost basis. remains strong and on behalf of the society I thank them Considering the importance of our current reserves for for their support of these awards. I would also like to thank ability of ASBMB to maintain its current range of activities, Sally Jay for her tireless efforts in securing continuing members should consider the following cost and income sponsor support for our awards. Interest on our accounts figures. Running costs for the Society at this point average remained steady in 2019–2020 due to stability in the $115,000 per year, with the bulk of the expenditure official interest rate. being National Office costs, SIG and state branch Net expenditure in the 2019–2020 financial year was contributions, costs for our awards and our publication, down $5,700 compared to the previous period (2018– the Australian Biochemist. On the income side, we are 2019), however the conditions for the last financial year looking at $95,000, which are membership fees (regular were atypical. We are fortunate that Sally and Chris and Sustaining Members), sponsorship for awards and Jay manage the National Office with a high degree of a small amount of bank interest. Consequently, we are effectiveness while keeping their costs relatively stable. running at an annual loss of $20,000 per financial year. Our flagship publication is the Australian Biochemist We have remained profitable the last few years entirely and it is available to members as a PDF. Tatiana Soares due to the profits generated from ComBio conferences, da Costa as the Editor of the Australian Biochemist, however with the move to holding ComBio every other along with Editorial Officer, Liana Friedman, are to year, our major income stream will be halved in the be commended for their work in putting the magazine future. Whilst we hold reserves of $310,000 at this point together. Reduced meeting costs were achieved by the in time, we are likely to suffer losses of over $20,000 Executive and Council holding teleconferences and for the year 2020–2021 and 2021–2022 before we will continue to improve the financial status of the Society. (hopefully) return to a profit making year in 2022–2023 The distribution of funds to the state and Special Interest with ComBio2022. I note that projected losses assume Groups was $3,180 below that in 2018–2019, due to stable membership numbers, which in the past were lower activity levels of the groups. heavily dependent on holding annual conferences. Due to the postponement of ComBio2020 we had In my role as the ASBMB Treasurer, I have many to access cash reserves ($100,000 was used), thus people to thank. Members of the ASBMB Executive substantially impacting our current assets. This was who are always constructive and supportive, Sally and required to provide additional seed funds for the operating Chris Jay (ASBMB National Office), Ian Price (ASBMB costs of ComBio2020 (which will now be ComBio2022), bookkeeper), Priestleys (ASBMB accountants) and Brian and to ensure we maintain sufficient cash to enable the Hiley (ASBMB auditor). day-to-day operations of the Society and continue to Professor Marc Kvansakul, Treasurer support activities. [email protected]
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 49 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 50 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 Our Sustaining Members
ASBMB welcomes the following Disclaimer new Sustaining Member: The Australian Biochemist is GENSCRIPT, SINGAPORE published by the Australian Society for Biochemistry and Molecular Biology Inc. The opinions expressed Labconco – Supplied by in this magazine do not necessarily Bio-Strategy represent the views of the Australian Society for Biochemistry and Protecting the user, the work-zone Molecular Biology Inc. and the laboratory since 1925. Make the Human and The Purifier Logic+ is a Biological Nature Healthier through Safety cabinet built with safety and Biotechnology with GenScript ergonomics in mind. The NSF-49 listed cabinet features an interior-mounted GenScript is the world’s leading colour LCD – full alerts and messages biotech company providing life are in line of sight with the user; bright, Expedeon Products Now sciences services and products. glare-free LED lighting; flush mounted Available from Abcam With gene synthesis, peptide, electrical receptacles; 10° angled Following the acquisition of protein, antibody and preclinical drug manual sash and user-programmable Expedeon’s Proteomics and development service capabilities, we start-up and shut-down. are internationally recognized as a Immunology business, Abcam now leading biotech company specializing in Labconco also offers a range of offer an extended array of antibody fundamental life sciences research and specialised ventilated enclosures for and protein conjugation kits, including early-phase drug discovery services. different applications such as working Lightning-Link® fluorescent dye, 22–25 As of June 2020, more than 51,000 with fine powders, chemical vapours, enzyme, oligonucleotide, latex and peer-reviewed journal articles cited animal bedding disposal and PCR metal kits. Simply pipette your antibody NOVEMBER GenScript’s services and products, setup. or biomolecule of choice into the vial of making GenScript the most frequently Sample concentration devices are lyophilized mixture containing the label cited Biotechnology company in the also available. of interest and incubate for just 20 2021 world. minutes (Lightning-Link® Fast range) Labconco’s freeze dryers cater to or 3.5 hours (Lightning-Link® range). For 2020, we have brought out the aqueous, solvent or acid containing GenScript cPass™ SARS-CoV-2 samples with its range of cold traps, In addition, InstantBlue® (ab119211) We are excited to welcome you to Neutralization Antibody Detection Kit, ranging in temperature and capacity. is a ready to use Coomassie protein also known as SARS-CoV-2 Surrogate With Lyo-works OS (Labconco stain for polyacrylamide gels. Its Christchurch, New Zealand for the Virus Neutralization Test (sVNT) Kit. It exclusive), know, in real time how unique mechanism of action stains proteins in 15 minutes, while leaving a 16th Congress of the Federation of is the first-in-the-world “rapid smart test your samples are doing and get kit”, with the capability of measuring consistently high-quality results. clear background eliminating the need Asian and Oceanian Biochemists functional neutralizing antibodies to fix, wash or destain. Formulated for (NAbs) within an hour in most research Centrivap concentrators use a safe use and easy disposal, it’s ready and Molecular Biologists. or clinical labs. The cPass™ technology combination of centrifugal force, to use straight out of the bottle and allows for the rapid detection of total vacuum, and heat to speed evaporation comes in convenient premixed one litre of small samples. RapidVap volumes. The one step, no washing, This will also be ASBMB’s annual neutralizing antibodies (NAbs) in a sample by mimicking the interaction evaporation systems combine block fixing, microwaving or destaining meeting in 2021. between the virus and the host cell. In heating, vortex shaking, vacuum protocol can detect down to 5ng bands order for a virus to infect a host cell, and nitrogen blowdown to dry down with a high signal to noise ratio with a viral receptor binding protein (RBD) samples or reduce to an endpoint no overstaining, is nontoxic, methanol first needs to interact with the host cell’s volume. and acetic acid free as well as being membrane receptor protein (ACE2). Whatever the task, Labconco has compatible with mass spectrometry. Peak Bodies To learn more, please visit a solution to keep you and your More information at www.abcam.com www.genscript.com, or email us at workspace safe. or please note our new phone number [email protected]. Bio-Strategy 1800 960 553 / (03) 9070 4707. 1800 008 453 Hosts [email protected] www.bio-strategy.com
For further information visit FAOBMB2021.ORG VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 51 Our Sustaining Members
BioNovus Life Sciences The Resolvex® A200 can also be David Antonjuk used for mass spectrometry, toxicology Ph: (02) 9484 0931 and proteomics sample preparation. Email: [email protected] To learn more about the Resolvex® Web: www.bionovuslifesciences.com.au A200 and applications, visit www. V5-Trap for the Isolation of tecan.com. Arrange a demonstration by V5-Tagged Proteins calling us on 1300 808 403 or send an email to [email protected]. ChromoTek has introduced the V5-Trap™ which is a Nanobody or VHH coupled to agarose and magnetic agarose for superior Having Issues Sourcing immunoprecipitation (IP) and Co-IP of Consumables for Nucleic V5-tagged proteins. Acid Extraction? The V5-tag is derived from the P and The Resolvex® A200 is an industry- V proteins of Simian virus 5 (SV5) and leading, compact standalone system is a popular epitope tag for the capture for semi-automated positive pressure As a member of ASBMB, you are and detection of V5-tagged proteins in processing. It combines programmable eligible to become a member of yeast, bacteria, insect and mammalian dispensing and pressure profiles, plate Laboratories Credit Union (LCU). cells. The V5-tag may be fused to detection, and safety features, that either the N-terminus, C-terminus of a require minimal human intervention. For a limited time, LCU has a special protein or be internal. The short linear In addition to the compact benchtop home loan offer for the members peptide sequence of the V5-tag is version, the Resolvex® A200 can also of ASBMB with LCU covering up to GKPIPNPLLGLDST and has a size of be integrated into Tecan’s industry- $1000 of legal and valuation fees. about 1.4kDa. leading liquid handling platforms, This is applicable for both purchases and refinances. You will find our home Benefit from the V5-Trap advantages providing a seamless workflow for high loan products – including fixed loans – for your next IP throughput applications. are very flexible and offer 100% offset • Very low background At Tecan, we have developed pre- accounts with no annual loan fees. • No heavy and light antibody chains programmed methods for many More information is available on our in gel popular nucleic acid purification kits website: www.lcu.com.au on the Resolvex® A200. Utilising • High specificity, high binding So who is LCU? capacity the hardware and reagents, we can automate elements of the tedious steps LCU was established by CSIRO staff • Extraordinarily stable even under involved with purification of nucleic in 1954 and has a branch located in harsh washing conditions acids with kits that are traditionally North Ryde, NSW. A credit union is a • Compatible with N-, C-terminal and processed via centrifugation or member-owned financial institution and internal V5-tag vacuum. we offer the same services as banks • Effective elution with V5-peptide Benefits include: but our profits go back to members • Recombinant Nanobody ensures through competitive interest rates, • Increased consistency due to consistent results fairer fees and community activities/ positive pressure sponsorships in our local area along The V5-Trap is a convenient, well • No disposable tips required, with the science community. LCU is characterized, and high-performing lowering consumable costs an approved deposit-taking institution tool; it is ready to use, for fast and • Easy change between different that is regulated by APRA under the specific IP of V5-tagged proteins. It is kits – connect up to 11 different Banking Act so your money is safe. compatible to downstream applications reagents and buffers to the same including mass spectrometric (MS) LCU was set up by scientists and we instrument at once analysis, ELISA, and enzymatic assays. continue to be involved through support V5-Trap’s pulldowns provide pure • Faster; down to 30 minutes per 96 of science awards and groups such extracts of V5-tagged protein without well plate as the CSIRO Alumni Scholarship, contaminating heavy and light chain • Standalone operation; intuitive RACI, AIP, MSA as well as Sustaining peptides as can occur with the use touchscreen interface so no need Membership of the ASBMB. for an extra PC of conventional antibodies. Effective If you would like to discuss the elution of bound V5-tagged proteins • Comparable yields to traditional LCU – ASBMB offer, or anything else can be conducted under denaturing methods regarding LCU please contact Sally on conditions (for SDS-PAGE/WB, MS) or • Compact benchtop solution that 9859 0585 or [email protected] under gentle, native conditions using easily fits in your lab hood V5-peptide.
PAGE 52 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 Our Sustaining Members
you confidence in the reliability of The Fluidity One‑W Serum has the instrument. Two-year standard the unique ability to independently warranty reflects the robustness of the quantify antibody affinity and system, giving you confidence in your concentration directly in patient results. The Azure CieloTM 3 and the serum which allows a deeper, more Azure CieloTM 6 allow you the flexibility accurate understanding of the to select a system that fits both your immune system. applications and your budget The Azure Cielo Real-Time Fluidity One-W Serum highlights: No external PC is required to run the PCR System • Characterisation of protein instrument. The data transmission is interactions in solution using TM The Azure Cielo 96-well real-time convenient, providing interactive forms microfluidic diffusional sizing (MDS) PCR systems from Azure Biosystems, such as USB, Ethernet, WiFi, etc, and • Ability to measure in complex combines high-quality PCR temperature can receive the experiment completion backgrounds such as minimally modules and excellent fluorescence notification and experiment data files diluted serum detection systems to provide your remotely. scientific research with highly accurate, • No binding artifacts or non-specific SciTech Pty Ltd sensitive, and reliable results. With a binding, no surface-constraints (03) 9480 4999 10.3” touchscreen interface, the Azure • Independent determination of [email protected] CieloTM 3 comes with 3 dye channel antibody concentration and affinity www.scitech.com.au filters while the Azure CieloTM 6 comes for a comprehensive immune with 6 dye channel filters. response assessment They are the qPCR systems of choice • Easy-to-use interface and for quantitative and qualitative gene consumable management expression analysis, miRNA analysis, • Disposable single use chips and genetic mapping, genetic fingerprinting, contained waste minimise risk of NGS library quantification, 3 or 6 cross contamination channel multiplex ability and pathogen Download application note: Accurate quantification. solution phase affinity profiling of a A fibre optic detection system scans SARS-CoV-2 antibody in serum here 16 wells simultaneously with the option https://www.fluidic.com/resources/ for multiplexing. solution-phase-affinity-profiling-of-a- SARS-CoV-2/ With intuitive touch screen control Fluidity One-W Serum Enables software, the host itself can be controlled In-solution Affinity Profiling ATA Scientific Pty Ltd independently, and the software can be The new Fluidity One-W Serum www.atascientific.com.au remotely monitored, allowing you to is a novel in-solution immunoassay [email protected] monitor the progress of the experiment platform that allows researchers to (02) 9541 3500 and obtain the experimental results in characterise and quantify antigen- real time. antibody interactions directly in Both systems are engineered for a minimally diluted serum. wide variety of qPCR applications, Traditional immunoassays such with high sensitivity and wide dynamic as ELISAs combine affinity and range. They can be customized concentration into a single, less- according to requirements, and can be precise measure known as titer, output, but not limited to: plate layout, which cannot readily distinguish PCR running program settings, raw between large numbers of weak- data map, amplification curve chart, binding antibodies and small numbers graphical display, statistical data, of strong-binding antibodies. Other experimental instructions, etc. Saved technologies which rely on attaching protocols make assay set up easy and antigens to surfaces have the ability reproducible. to measure affinity in purified systems, CieloTM’s optics and thermal block but experience difficulty doing so in are designed to deliver the same complex backgrounds such as plasma uniformity and reproducibility over at and serum due to non-specific binding least 1000 qPCR experiments, giving and other surface constraints.
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 53 Our Sustaining Members
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PAGE 54 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 Our Sustaining Members
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VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 55 ASBMB Council 2021
PRESIDENT PAST PRESIDENT Professor Jacqui Matthews Professor Joel Mackay 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 6025 Ph (02) 9351 3906 Email: jacqueline.matthews@ Email: joel.mackay@sydney. sydney.edu.au edu.au
TREASURER SECRETARY Professor Marc Kvansakul Associate Professor Dominic Ng Department of Biochemistry and School of Biomedical Sciences Genetics University of Queensland La Trobe Institute for Molecular ST LUCIA QLD 4072 Science Ph (07) 3365 3077 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.combio.org.au/combio2022
@ITSASBMB @ComBio2022 ComBio
PAGE 56 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020 Directory
COUNCIL FOR STATE SPECIAL INTEREST 2021 REPRESENTATIVES GROUPS PRESIDENT AUSTRALIAN CAPITAL TERRITORY ADELAIDE PROTEIN GROUP Professor Jacqui Matthews Dr Christina Spry Chair: Dr 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 6025 Ph (02) 6125 0640 Email: [email protected] Email: [email protected] Email: [email protected] AUSTRALIAN YEAST GROUP PAST PRESIDENT NEW SOUTH WALES Chair: Dr Alan Munn Professor Joel Mackay Dr Laura Sharpe 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 3906 SYDNEY 2052 NSW Email: [email protected] Email: [email protected] BIOCHEMICAL EDUCATION Chair: Dr Nirma Samarawickrema TREASURER QUEENSLAND Monash University Professor Marc Kvansakul Associate Professor Michael Landsberg CLAYTON VIC 3800 Department of Biochemistry and Genetics School of Chemistry & Molecular Biosciences Ph (03) 9902 0295 La Trobe Institute for Molecular Science University of Queensland Email: [email protected] La Trobe University ST LUCIA QLD 4072 BUNDOORA VIC 3086 Ph (07) 3365 3756 CELL ARCHITECTURE Ph (03) 9479 2263 Email: [email protected] Chair: Associate Professor Thomas Fath Email: [email protected] Dementia Research Centre SOUTH AUSTRALIA Macquarie University SECRETARY Dr Melissa Pitman NORTH RYDE NSW 2109 Associate Professor Dominic Ng Centre for Cancer Biology Email: [email protected] School of Biomedical Sciences SA Pathology & University of South Australia University of Queensland ADELAIDE SA 5001 MELBOURNE PROTEIN GROUP ST LUCIA QLD 4072 Ph (08) 8302 7892 President: Dr Michael Griffin Ph (07) 3365 3077 Email: [email protected] Biochemistry and Molecular Biology Email: [email protected] Bio21 Institute, University of Melbourne TASMANIA PARKVILLE VIC 3010 EDITOR and Dr Iman Azimi Ph (03) 9035 4233 CHAIR OF COMMUNICATIONS College of Health and Medicine Email: [email protected] Dr Tatiana Soares da Costa University of Tasmania Department of Biochemistry and Genetics HOBART TAS 7001 METABOLISM AND MOLECULAR La Trobe Institute for Molecular Science Ph (03) 6226 1747 MEDICINE GROUP La Trobe University Email: [email protected] Chair: Dr Nigel Turner BUNDOORA VIC 3086 UNSW Sydney Ph (03) 9479 2227 VICTORIA KENSINGTON NSW 2052 Email: [email protected] Dr Laura Osellame Ph (02) 9385 2548 Department of Biochemistry and Genetics Email: [email protected] EDUCATION REPRESENTATIVE La Trobe Institute for Molecular Science Dr Nirma Samarawickrema La Trobe University PERTH PROTEIN GROUP Department of Biochemistry and Molecular BUNDOORA VIC 3086 Chair: Associate Professor Joshua Mylne Biology Ph (03) 9479 3658 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 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 February 2021 Ph (02) 9685 9926 Email: [email protected]
VOL 51 NO 3 DECEMBER 2020 AUSTRALIAN BIOCHEMIST PAGE 57 PAGE 58 AUSTRALIAN BIOCHEMIST VOL 51 NO 3 DECEMBER 2020