< PreviousRESEARCH THEMES 9 CENTRE MEMBERS 259 PUBLICATIONS 169 PATENTS 15 AWARDS, PRIZES AND FELLOWSHIPS 42 WORKSHOPS, TRAINING SKILLS- BASED & TECHNICAL COURSES OFFERED 41 INVITED CONFERENCE TALKS AND PRESENTATIONS 87 IN EXTERNAL FUNDING GRANTS $22M OVER PUBLICATIONS IN TOP JOURNALS 24 TITLE2019 AT A GLANCE 10IMAGING COE 2019 ANNUAL REPORTMESSAGE FROM THE DIRECTOR “…. because as we know, there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns—the ones we don’t know we don’t know.” Donald Rumsfeld, US Defence Secretary, February 12, 2002 PROF. JAMES WHISSTOCK ARC AUSTRALIAN LAUREATE FELLOW NHMRC SENIOR PRINCIPAL RESEARCH FELLOW, DEPARTMENT OF BIOCHEMISTRY & MOLECULAR BIOLOGY, MONASH UNIVERSITY The beginning of 2020 marks the last year of our operation as an Australian Research Council Centre of Excellence, however, more than we could ever have anticipated, this year represents the beginning of a crucial new chapter going forward for our Imaging Centre research community. 1 Crystal structure of the SARS-CoV-2 non-structural protein 9, Nsp9., D. R. Littler, B. S. Gully, R. N. Colson, J. Rossjohn., bioRxiv 2020.03.28.013920 2 Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2., R. Yan, Y. Zhang, Y. Li, L. Xia, Y. Guo, Q. Zhou., Science, 2020, pp. 1444-1448 3 Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation., D. Wrapp, N, Wang, K. Corbett, J.A. Goldsmith, C. Hsieh, O. Abiona, B.S. Graham, J.S McLellan., Science, 2020, pp. 1260-1263 As I write this message, the enormous imperative for basic scientific research is highlighted by the massive global effort to control the virus that causes COVID-19. Indeed, our attempts to limit the spread of SARS-CoV-2 can be divided into at least five broad overlapping areas – socio-political, community, economic, clinical and basic research. With regards to the latter, for the past four months the news media and air waves have been regularly filled with scientific terms and infographics that are largely unfamiliar to the lay community – antigens, immune cells, protein structures, spike proteins and cytokines to name a few! It is also notable that the imaging approaches developed over the past few decades, many of which were at the time regarded as classic examples of disruptive technology, are now (we hope!) playing a central role in disrupting the advance of the SARS-CoV-2 virus. For example, structural genomic pipelines are allowing all of the individual proteins encoded by SARS-CoV-2 genome to be rapidly determined. These include classic drug targets such as proteases, but also SARS-CoV-2 proteins that are functionally less well understood. Our own Centre scientists and partners at the Australian Synchrotron have contributed to these global efforts, with the X-ray crystal structure of SARS-CoV-2 non-structural protein-9 being released in late March [1] . Similarly, cryo-electron microscopy research has yielded important results with unprecedented speed – with the first near- atomic resolution structures of SARS-CoV-2 spike proteins alone and in complex with its receptor on human cells being released by US- and China- based groups in January [2][3] – just weeks after the initial viral genome had been sequenced. When considering these advances, it is worth remembering that barely 25 years ago determining a single structure was regarded as a mammoth undertaking requiring many years of effort. Now the combination of advanced cryo-electron microscopes, crystallisation robotics, super-bright synchrotron sources, next generation sequencing machines, and sophisticated software pipelines together with advanced computational capacity has meant that SARS-CoV-2 structures can be determined and released in a matter of days. This plethora of structural and genomic data will now enter a well-trodden pipeline of drug discovery – both in terms of using or adapting existing therapeutics and developing new molecules. Here, because of the nature of clinical trials and safety, the rate of progress will be necessarily more modest. However, as we work on through the COVID-19 crisis and beyond, it is anticipated that the effort to assemble an arsenal of antiviral drugs that target SARS-CoV-2 and related pathogens will continue unabated. I’d like to end my message by reflecting on the words of the US politician Donald Rumsfeld – which were very controversial at the time because of the geo-political context in which they were voiced – but that are nevertheless rather applicable in the context of scientific discovery. Much of our collective effort as scientists is focused on understanding and studying “known knowns”, and “known unknowns” – indeed, the nature of scientific funding generally tightly focuses efforts in directions that are most likely to yield immediate and tangible “impact”. However, history reveals that many of the most startling game changing scientific discoveries, and many of the crucial tools that are now being put into battle against the spread of SARS-CoV-2 and to treat the disease COVID-19, did not arise through a logical focus on research judged at the time as being the most likely source of impact in society. Instead, curiosity driven research and serendipity has so often led to the revelation of unknown unknowns – things that we were neither aware of nor understood at the time of discovery. As we delve and image ever more deeply into the inner working of cells and complex systems such as the immune system it is to be anticipated that many more surprises and developments are in store that will be regarded by our descendants as being indispensable… I wish you all the very best during the course of this extremely difficult year, and I hope that your family, friends and colleagues are safe and well. 11IMAGING COE 2019 ANNUAL REPORTSTRENGTHENING LINKAGES: INTERNATIONAL FRAUNHOFER JANSSEN EMBL LINAC COHERENT LIGHT SOURCE (LCLS) GERMANY SWITZERLAND BELGIUM UNITED KINGDOM UNITED STATES OF AMERICA WARWICK UNIVERSITY THERMO FISHER JANSSEN ROCHE EUROPEAN XFEL (EUXFEL) DESY ZEISS 12IMAGING COE 2019 ANNUAL REPORTCHINA AUSTRALIA MELBOURNE SYDNEY BRISBANE SOUTHEAST UNIVERSITY CENTRE NODE CENTRE NODE ANSTO WOLF BIOTHERAPEUTICS EMBL AUSTRALIA CENTRE NODE The Imaging CoE has been increasing its collaborations and connections, nationally and internationally, every year. This map is a graphical representation of our current linkages in Australia and internationally with a range of businesses, research institutes and universities. These are strategic relationships that work towards fostering new opportunities and ensuring we are working with the best minds possible for industrial and academic partnerships. Our work with these partners encompasses a wide range of activities, from sample preparation, imaging data acquisition, data analysis and visualisation, through to interpretation, application, and commercialisation. 13IMAGING COE 2019 ANNUAL REPORTIMAGING COE STUDENTS GAIN INTERNATIONAL RESEARCH EXPERIENCE Imaging CoE PhD students, Ms Holly Ung and Mr Blake Mazzitelli completed a three-month research placement at Fraunhofer IZI-BB in Potsdam, Germany. Both students studied and implemented Fraunhofer IZI-BB’s optimised system for Cell- Free Protein Synthesis (CFPS). The research placements mark a significant milestone in the partnership between Monash University and the Imaging CoE with Fraunhofer IZI-BB. By developing a novel pipeline of cell-free protein-synthesis to molecular imaging, researchers expect to be able to address previously unanswerable research questions. As part of the Imaging CoE’s commitment to fostering the next generation of scientists, the research placements offered the students an opportunity for international exposure and allowed them to gain valuable insights into the German approach to applied research. Ms Ung and Mr Mazzitelli were the first students to participate in the program. WE LEARNT MANY NEW SKILLS… “We honed in on current skills, and came away with connections that we would not have built outside of this program. The placement was hugely beneficial to our careers in biomedical science,” Mr Mazzitelli said. While CFPS technology has existed previously in various forms, the Department of Cell-free and Cell-based Bioproduction at Fraunhofer IZI-BB has spent many years optimising the system for the generation of disease-related human proteins. Many of these proteins are typically unable to be generated in cell-based systems and, indeed, many commercial CFPS systems. AS A YOUNG FEMALE SCIENTIST… “It was an incredible learning experience. My two supervisors were inspiring women who are pioneering the development of this powerful technology. Their words of encouragement and support gave me the independence and confidence to contribute to the scientific community in this exciting era, where more and more women are leaders,” Ms Ung said. “As scientists at the Imaging CoE, our goal is to obtain a detailed understanding of the mechanisms by which various proteins function, as well as the molecular events that allow these proteins to cause diseases such as autoimmune disease and cancer,” Mr Mazzitelli said. “A significant bottleneck to our research is the difficulty in expressing many of these disease-related proteins for further studies. CFPS, therefore, presents as a promising technique to overcome these difficulties.” The goal of this research placement was to test some of the most difficult-to-express proteins in the Fraunhofer IZI-BB CFPS system. Ms Ung and Mr Mazzitelli were given a first-hand look at the powerful capabilities of CFPS. They were able to synthesise various proteins otherwise unable to be generated in traditional systems, as well as confirm the functionality of these proteins by harnessing the impressive infrastructure and machinery housed at Fraunhofer IZI-BB. The work allows various projects to push forward to the molecular imaging stage, primarily undertaken at the Monash Biomedicine Discovery Centre, including the Monash Micro Imaging (MMI) platform, FEI Titan Krios and the Australian Synchrotron. In addition to breaking down scientific barriers, the experience was incredibly beneficial for Ms Ung and Mr Mazzitelli’s professional development. Integrating into a new research group and learning novel techniques providing a different perspective into biomedical sciences. STRENGTHENING LINKAGES: INTERNATIONAL CONT. 14IMAGING COE 2019 ANNUAL REPORTIMAGING COE CONTINUES TO STRENGTHEN INTERNATIONAL COLLABORATIONS In November, the Imaging CoE welcomed a delegation of scientists from Fraunhofer IZI-BB. Dr Dagmar Schlenzig, Claudia Spahn and Anne Zemella were the second group of researchers to visit since the partnership between Fraunhofer and the Imaging CoE was established. The scientists visited for ten weeks, and worked on ongoing collaborative research projects with Imaging CoE researchers, the Cryo-EM facility and Fraunhofer’s cell-free protein synthesis technology. Cryo Electron Microscopy experts, Dr Schlenzig and Ms Spahn, collaborated with the Imaging CoE’s Dr Chris Lupton and Charles Bayly-Jones. “It was one of the most successful projects I’ve worked on, particularly given the short amount of time we had during this visit. Throughout the project I worked with Dr Schlenzig and Ms Spahn to produce a lot of data, which has resulted in four novel protein structures,” Dr Chris Lupton said. Ms Zemella collaborated with Dr Ruby Law and Mr Blake Mazzitelli to implement Fraunhofer IZI-BB’s novel Cell-Free Protein Synthesis (CFPS) technology. By simultaneously utilising the Cryo Electron Microscopy platform at Monash University, the collaboration introduced a new pipeline of CFPS to structural biochemical analysis, the first of its kind in Australia. Ms Zemella was also part of a crossdisciplinary collaboration with A/Prof. Claudia Nold (Hudson Institute of Medical Research), Prof. Marcel Nold (Department of Paediatrics, Monash Health) and Dr Andrew Ellisdon (Biomedical Discovery Institute, Monash University), working on the IL-37 receptor complex. IMAGING COE INVITED TO HEALTH CAPITAL BERLIN BRANDENBURG In September, four Imaging CoE Associate Investigators were invited to speak at the ‘New and Emerging Technologies – Biotech meets Medicine’ conference in Potsdam, Germany. Organised by Glyconet Berlin Brandenburg and hosted at the Fraunhofer Conference Centre, the three-day event provided insights into the set-up of the Berlin Brandenburg healthcare cluster as it develops into one of Europe’s leading biotech and pharma innovation hubs. With pivotal players active in the region, this emerging innovation hub focuses on strengthening local and international cooperations between science, industry, clinics and biotech companies, as well as accelerating technology transfers and developing interdisciplinary technologies to leverage new growth areas in the life sciences. Showcasing the scientific excellence, interdisciplinarity and global relevance of Australian research, A/Prof. Claudia Nold from the Hudson Institute of Medical Research and international partner, Dr Stefan Kubick from Fraunhofer IZI-BB co-chaired the Advanced Imaging Techniques session. The session featured talks from Imaging CoE Associate Investigators Dr Steve Lee, ANU College of Engineering and Computer Science, on ‘Advances in Micro-Imaging methods for studying Haemostasis’; Prof. Scott Mueller from The University of Melbourne spoke about ‘Imaging the dynamics of immune responses to virus infection’; Prof. Marcel Nold from Monash University / Hudson Institute of Medical Research provided a clinical angle presenting on ‘Advanced Imaging Techniques – the End-User’s Perspective’. Dr James Pearson from the National Cerebral and Cardiovascular Center Research Institute in Japan who works very closely with the Australian and Japanese Synchrotrons spoke about the ‘Application of synchrotron microangiography to fast high-resolution cardiopulmonary vascular imaging’. The visit to Germany also provided an opportunity for the researchers to visit the Fraunhofer IZI-BB facilities and to catch up with their respective collaborators to progress joint projects. The Imaging CoE Chief Operating Officer, Annette Wittmann, joined the Australian delegation to strengthen the Centre’s visibility and engagement in German networks of research excellence. A new five-year cooperative research agreement between Monash University and the Fraunhofer IZI and IZI-BB is under development. STRENGTHENING LINKAGES: INTERNATIONAL CONT. (L-R) Claudia Spahn, Dagmar Schlenzig and Anne Zemella were at the CAVE 2, Monash University, Clayton Campus. (L-R) Prof. Dr.Stephan Hinderlich, University of Applied Sciences, Berlin, Dr Stefan Kubick, Fraunhofer IZI-BB, Dr Manuela Schuetze, Glyconet Berlin Brandenburg, Dr Dagmar Schlenzig, Fraunhofer IZI. Imaging CoE researchers visiting Fraunhofer IZI facilities. 15IMAGING COE 2019 ANNUAL REPORTPARTNERSHIP WITH ANSTO’S AUSTRALIAN SYNCHROTRON The Australian Nuclear Science and Technology Organisation (ANSTO) is the home of one of Australia’s most significant pieces of research infrastructure, the Australian Synchrotron. Thousands of scientists from industry and academia benefit from accessing the state-of-the-art instruments every year. ANSTO leverages great science to deliver big outcomes, partnering with scientists and engineers, and applying new technologies to provide real-world benefits. In January, Imaging CoE staff were involved in the installation of the Eiger2 9M which was installed on the MX1 beamline. The Eiger is an x-ray detector that has improved the speed and quality of data collection. It operated during 2019 and produced excellent data quality and high throughput for Imaging CoE researchers and other users. Dr Jun Aishima, Imaging CoE Postdoctoral Fellow based at the Australian Synchrotron, revised the automation code that improved results for macromolecular (MX) and chemical (CX) beamline users. This code processes data as it is collected, which minimises potential collection issues and alerts users to alter their data acquisition strategy. The revised code enabled users to undertake an improved collection strategy and maximise their data quality. A project to build a new MX3 beamline began in July. The MX3 beamline will be a high-flux microfocus MX beamline with a very small beam and a high degree of automation. The MX3 beamline will support a traditional robot mounted single crystals on pins, fixed-target serial crystallography on silicon chips, and an injector system. To ensure that the new beamline meets user expectations, staff who are developing the new MX3 beamline are involved in ongoing consultations with the scientific community and users. Completion of the MX3 beamline project is expected in early 2023, with first user access from July 2023. The user program will begin as a fraction of the available beam, and increase over 12 months. The MX3’s in-tray screening capability will be linked with other Australasian crystallisation facilities, with an aim to allow for easy and automated screening of trays. The MX3 may have an option for “Tray Tuesdays”, where trays are automatically screened on the first day of the beam, and results are automatically uploaded online for users to optimise crystals. A high degree of automation is planned for the MX3 with automated crystal location and collection, and automated data processing and merging. Opposite right middle: (L-R) Kate Smith and Ali Chahine Z-first MX1 Eiger user. STRENGTHENING LINKAGES: NATIONAL 16IMAGING COE 2019 ANNUAL REPORT17IMAGING COE 2019 ANNUAL REPORTAUSTRALIAN SYNCHROTRON OPEN DAY Every two years the Australian Synchrotron opens its doors to the public and allows the community to go behind the scenes and walk through its facilities. Last October, people had the unique experience to tour the Australian Synchrotron and speak to researchers and technicians stationed at each of the Synchrotron’s nine beamlines. It was also an opportunity for the Imaging CoE to highlight its collaboration with ANSTO scientists. The Australian Synchrotron is one of Australia’s most important pieces of scientific infrastructure for biomedical research. The $200 million facility houses an impressive number of scientific researchers and equipment that enables scientists to peer into the nanoscopic scales of molecules, all the way through to dissecting mummified objects that are too delicate to touch. Scientists from around Australia and across the world, travel to the Synchrotron each year to access its facilities for their research. The open day was fun for children and adults. Researchers led tours, and people experienced hands on interactive experiments, manipulated subatomic particles and discovered Synchrotron science. Top: (L-R) Laura D’Andrea and Charles Bayly-Jones from Monash University talking to visitors at the Synchrotron. Bottom: Dr Dene Littler, from Monash University representing the Imaging CoE at the event. STRENGTHENING LINKAGES: NATIONAL CONT. 18IMAGING COE 2019 ANNUAL REPORTINFRASTRUCTURE: MAKING ADVANCED MICROSCOPY PLATFORMS ACCESSIBLE Monash University, the ARC Centre of Excellence in Advanced Molecular Imaging Administering Organisation, became host to the new and only Victoria node of Microscopy Australia, a consortium of university-based microscopy facilities that enables access to an array of high-end microscopy platforms and associated technical expertise in strategic locations to efficiently service Australia’s microscopy needs. Monash University joined the ARC Imaging CoE’s University of Queensland and University of New South Wales nodes as part of the Microscopy Australia association. The new node, which provides access to state-of-the-art microscopy infrastructure and skilled staff at Monash University through the Microscopy Australia framework, was celebrated in an official launch event in September at Monash’s Clayton Campus. Addressing the guests representing the wider university microscopy research community, Imaging CoE Board Member and Monash University’s Vice-Provost (Research & Research Infrastructure) Prof. Ian Smith said the Victorian offering of a Microscopy Australia node is, in fact, a partnership between the Monash Centre for Electron Microscopy and the Ramaciotti Centre for Cryo-Electron Microscopy. “At a molecular level, Monash has also been at the forefront of cryo-electron microscopy, with the country’s first and most powerful microscope for biological electron microscopy, the Titan KRIOS. Cryo-EM is a technique so powerful that it won the original developers a Nobel Prize in Chemistry in 2017,” said Prof. Smith. “The structural and cell biology community is very pleased with the instrumentation and access that this new collaboration provides and we are looking forward to seeing the impact that this has in the Australian scientific community,” said Prof. Whisstock, Director of the ARC Imaging CoE. Microscopy Australia CEO, Prof. Julie Cairney also emphasised the importance of supporting research access to these instruments, noting that by providing open access policy to these facilities under Microscopy Australia, this infrastructure can now be of great value to a broader user base. “Open access to Monash’s significant national-scale research infrastructure will be extremely valuable not only for Victorian researchers but also for the wider Australian scientific community” said Prof. Cairney. “We welcome the excellence of the people, infrastructure and processes that Monash University will bring into Microscopy Australia. We look forward to working together and leveraging the value that all partners bring to this NCRIS facility in support of excellent research both within Australia and internationally,” said Prof. Cairney. ARTICLE SOURCE: R&RI Monash University View Article Top: (L-R)Grainne Moran, Lisa Yen, Georg Ramm, Robert Robinson, James Whisstock, Ian Smith, Marc Parlange, Julie Cairney, Jo Etheridge, Paul Bonnington, Greg Smith, Jim Patrick. Bottom: Prof James Whisstock, Director of the ARC CoE in Advanced Molecular Imaging. STRENGTHENING LINKAGES: NATIONAL CONT. 19IMAGING COE 2019 ANNUAL REPORTNext >