Kira Biotech Series A funding press release

Some of the main news items:

• Discover why some Australians are more likely to have cardiovascular disease
• Sydney hosts International Asian Oceanic CMT Conference
• Young Investigator Award for Andrology Research into Male Fertility
• A Rewarding Partnership – NSW Ministery of Health Grant
• Sacrifice Was Not In Vane – An edited version of an address given by ANZAC Research Institute chairman, Prof. Bob Lusby.

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Commemorating ANZAC Day

The word ANZAC stands for Australian and New Zealand Army Corps. The soldiers who fought together became known as Anzacs, exemplifying a tradition of service, selflessness and mateship. April 25th was officially designated ANZAC Day in 1916 by Australia and New Zealand. It is a national holiday in both countries and a day of remembrance. Commemorative services are held each year at dawn, the time of the original Gallipoli landing.

With the start of the Second World War and other conflicts including those of Korea, Vietnam, Afghanistan and Iraq; ANZAC Day has been expanded to include remembrance of all servicemen and women who have given so much to Australia.

The health and medical ANZAC Research Institute was named after and in remembrance of this tradition. This ANZAC Day we commemorate and learn from the sacrifice of so many Anzacs who gave so much.

Remembering at the Kokoda Track Memorial Walkway

Reefs laid during the Kokoda Memorial Track ANZAC Service.

http://anzac.edu.au/our-newsletter/

http://anzac.edu.au/wp-content/uploads/2019/03/AnzacDiscoveryMar2019_online.pdf

Neurobiology group research team up with Raijin to study Inherited peripheral neuropathies.

High Performance Computing (HPC) are banks of specialist computers with large amounts of cores, memory, interconnects and fast storage. Raijin, named after the Shinto God of thunder, lightning and storms, is a hybrid Fujitsu Primergy and Lenovo NeXtScale high-performance, distributed-memory cluster, located at the National Computational Infrastructure (NCI) facility in Canberra. Raijin@NCI is from funding from the Australian Government, through its Super Science Initiative (under the EIF Climate HPC Centre Funding Agreement between the Commonwealth of Australia and the Australian National University), as well as through the 2015-16 Agility Fund of the National Collaborative Research Infrastructure Strategy. Grants are administered through Intersect.

The Neurobiology group at the ANZAC have recently been awarded a grant for to utilise resources at Raijin@NCI for research into Inherited peripheral neuropathies (IPNs). The aim of their research is to identify dysregulated genes in families that suffer from this genetic condition to improve diagnosis and treatment.

On the 18th of October, the ANZAC Research Institute held its 17th Annual Symposium on “Lessons from the Concord Health and Ageing in Men Project (CHAMP)”. The keynote speakers were Professor Bob Cumming who presented an overview of the history and results of the project, then followed by:

• Vasi Naganathan presenting on “Geriatric Syndromes in Older Men”,
• Ben Hsu presenting on “Androgen Status of Older Men – Cause or Consequence of Poor Health”,
• Fiona Stanaway presenting on “Health of Italian-Born Older Men”,
• David Le Couteur AO presenting on “Nutrition, Obesity and Lifespan”,
• Clive Wright presenting on “Oral Health of Older Men”.

The CHAMP project is a multidisciplinary epidemiological study and was designed to provide a wide range of new information about the health of older men. CHAMP began in 2005 when 1705 men, aged 70 years and over, were recruited to the study and interviewed for baseline results. Since then, follow ups have been conducted every two to three years. It is one of the world’s largest ongoing older men’s research projects.

The symposium presented how CHAMP continues to provide a wealth of research opportunities in basic science, clinical medicine, epidemiology and psychosocial aspects of ageing.

A research equipment grant of $365,000 from the Cancer Institute of NSW has enabled the ANZAC Research Institute to purchase an incredibly powerful microscope which allows scientists to examine cells within living animals.

A research equipment grant of $365,000 from the Cancer Institute of NSW has enabled the ANZAC Research Institute to purchase a remarkably powerful microscope which allows scientists to examine cells within living animals. Already the high speed, multichannel fluorescence microscope is providing state of the art images and assisting researchers in many fields to advance their projects.

The application for the equipment grant was co-ordinated across ten research groups within the ANZAC Research Institute, the Asbestos Diseases Research Institute and the Centenary Institute, all of which are now seeing significant benefits.

Dr Vivien Chen, Staff Specialist Haematologist at Concord Hospital and Leader of the Platelet and Thrombosis Research Laboratory at ARI, says recent developments in microscopy have contributed to astonishing advances in scientists’ ability to produce images of biological processes.
“We can put a live mouse onto the platform, then, by fluorescent tagging the cells, activation markers, or proteins of interest, we can directly visualise events occurring in real time within our animal models.

“My group is interested in the process of blood clot formation in the context of heart attack, stroke or cancer, all condition which have associated deep venous thrombosis. Using this microscope, we can image the blood flow within a vessel and watch the blood clot. For the first time, we can measure the rate of individual platelets as they come in to form the clot and monitor the stabilising proteins as they form around the blood clot.

“Thus, when we develop drugs for inhibiting blood clot formation, in our search for therapies for improving outcomes after a heart attack or stroke, or for prevention of deep vein thrombosis or potentially fatal pulmonary embolism, we don’t just have to test it in a test tube. We can evaluate them in a live model where all the components of the clotting system are together: the blood vessel, the blood components and the forces of blood flow. This becomes a very powerful experiment bringing us much closer to translation to the clinic.”

Dr Chen explains that the microscope also allows researchers to look at the underlying mechanism of biological processes.

“So if you’re interested in a particular protein and a particular pathway you can modify that pathway either genetically or pharmacologically, and by comparing that mouse with a wild-type mouse with the pathway intact, you can get some powerful information about how that pathway is working in that biological system.”

The new equipment is proving to be invaluable in cancer research. Being able to view a live animal means, for example, that researchers can watch to see how a drug is able to get within a tumour. The team at the Asbestos Diseases Research Institute is using fluorescence to see how deeply a drug penetrates a tumour and which cells it is getting into. The Biogenerentology group can directly image drugs as they are delivered to the liver cells.

Another example of the use of this powerful microscope is the Northcott Neurogenetics group who are investigating inherited forms of nerve damage due to inherited defects in pathways that nerves require to function over long distances. To mimic that disease in the laboratory, those neuroscientists working on new treatment targets uses worms that glow fluorescently so they can study these living organisms viewed under the microscope. By this means the scientists can study for the first time the direct effects of an abnormal gene or protein suspected of causing human nerve damage on the worm’s ability to move normally.

As Dr Chen says, the new equipment has been a welcome addition to the facilities available at the ANZAC Research Institute, enabling researchers in various fields to continue to contribute at the highest level internationally. In particular, it provides a valuable step in the process of translating the findings in fundamental research made at the Institute into the development of new treatments for disease.

Professor Derek Hart was a passionate, driven and inspired clinician scientist who had a consuming motivation to improve medical care through a life committed to medical research. Through a career full of achievements he made many important discoveries that together built his grand vision for immune therapies based on dendritic cells as novel therapeutics for solid and liquid cancers as well as immunosuppression and controlling graft vs host disease.

Derek Hart was born and educated in New Zealand, graduating in 1976 with distinction and numerous awards from the Faculty of Medicine, University of Otago. After graduation he initially started on surgical training before winning a Rhodes Scholarship and, in 1981, submitting his DPhil on transplantation antigens while working at the Nuffield Department of Surgery, Oxford University. There he met his wife, Dr Georgina Clark, an Australian post-doctoral fellow co-worker forging a formidable career-long scientific team. Through these studies, Derek was particularly proud to have been the first to identify human dendritic cells, critical effectors in immune rejection, soon after Ralph Steinman’s 2011 Nobel Prize-winning discovery of dendritic cells in the mouse. In 1981 Derek returned to Christchurch to gain specialist medicine and pathology qualifications as a haematologist (FRACP, FRCPA) setting up a research-focussed Bone Marrow Transplantation Unit. In 1998 he was appointed the inaugural Professor/Director of the Mater Medical Research Institute in Brisbane where he served for a decade before being recruited in 2000 to the ANZAC Research Institute and the University of Sydney as Professor of Transplantation and Immunotherapy and NHMRC Senior Principal Research Fellow. In Sydney, at the ANZAC Research Institute he established the Dendritic Cell Research group which flourished under his inspiring and energetic leadership propelling it to become the focal point of a wide network of collaborating scientists at Concord, Westmead and RPA Hospitals supporting over 25 senior basic and clinical scientists, postdoctoral Fellows and students. Over his career Derek made many important discoveries and “firsts” as well as winning awards and honours in the course of training numerous clinician scientists as well as basic scientists, being equally at home in both domains. In recent years, he chaired the Ramaciotti Scientific Advisory Committee. Like all contemporary medical researchers he suffered regular mixed success in the peer-review grant system but the thought of giving up or changing direction never crossed his mind. Derek was also very active in commercialising his discoveries taking out key patents and establishing, in 2013, a spin-off company Dendrocyte BioTech which works towards developing new dendritic cell-based immune therapies.

Derek Hart lived and worked by his own high standards with a seemingly inexhaustible drive for scientific achievement and excellence. His legendary work habits derived crucial support from his resilient wife and scientific partner Georgina and his two cherished children Olivia and James. With characteristic courage and tenacity, Derek faced his final illness for over a year without flinching or self-pity. Instead, he redoubled his efforts in science and commercialisation including overseas travels to meet colleagues, investors and biotech companies as well as the careful installation of succession plans to secure his legacy of novel immune therapies. That legacy will be continued not just by the network centred on his Dendritic Research Group but also by the legion of scientists he trained in Christchurch, Brisbane and Sydney now spread worldwide. The world of medical research is a better place for Derek’s unequivocally committed life. He and his indomitable drive will be missed beyond measure.

Professor David Handelsman
Director
ANZAC Research Institute

Dr Andrew Burgess, an experienced cell biologist who is the Institute’s new Microscopy and Cytometry Manager, has been awarded a grant of $398,049 over three years by the National Breast Cancer Foundation to further his research into the genetic background of breast cancers.

A primary driving force behind the initiation and ongoing development of breast cancer is the activation of oncogenes, genes with the potential to cause cancer. Dr Burgess explains that oncogenes act like a car accelerator, driving excessive growth and spreading of the cancer cells throughout the body. Consequently, identifying new oncogenes and determining their functions is essential for understanding how breast cancers grow and spread.

“We recently identified a novel oncogene called MASTL that is amplified and overexpressing up to 45% triple-negative breast cancers (TNBC). Importantly, increased MASTL correlates with higher grade, unstable tumours and poor patient survival. Our preliminary data shows that MASTL is able to drive normal breast cells to grow and spread abnormally.

“Conversely, removal of MASTL from TNBC cells reverses the abnormal growth and spreading. Initial analysis of the underlying mechanisms suggests that MASTL rewires key signalling pathways in breast cells and is essential for regulating how cells duplicate their DNA. We hypothesise that MASTL is an ideal candidate to develop inhibitors, as blocking MASTL would prevent breast cancer growth and spreading, and enhance response to current chemotherapies, leading to improved patient survival.

“The purpose of this project is to better understand the mechanisms by which MASTL drives breast cancer, confirm that targeting MASTL can successfully block breast cancer in mice models, and to establish the tools necessary to develop specific inhibitors of MASTL that could be used to treat breast cancer.”

Dr Burgess expects this project will primarily benefit patients with TNBC, especially metastatic disease. These patients are normally unable to undergo curative surgery, are unresponsive to hormone therapy, and therefore chemotherapy is the only treatment option. Unfortunately, the majority (~80%) of patient tumours do not respond to current chemotherapy treatments, and very few new treatments have been developed. Consequently, metastatic TNBC has some of the lowest overall survival rates for breast cancer and these have not improved in the past 20 years.

“There is a significant need to identify new targets for TNBC in order to improve these worst-case patients. We believe that MASTL represents a promising new target that could be used to improve the outcomes for TNBC patients.”

In 2017 it was estimated that almost 18,000 Australians (including about 150 men) would have been diagnosed with breast cancer, and at least 3000 deaths would be recorded.

Dr Burgess joined the ANZAC Research Institute in 2017, after five years at the Kinghorn Cancer Centre within the Garvan Institute of Medical Research. His career began in 1998 as an honours student at the Queensland Institute if Medical Research, and after graduating with 1st class honours, he studied for a PhD at the University of Queensland. In 2004 he was awarded a prestigious NHMRC C J Martin fellowship, which took him to the French National Research Centre in Montpellier. Two additional French fellowships allowed him to remain in France for seven years, continuing to explore the basic mechanism of how cells control the division process. In 2012 Dr Burgess received a five-year Fellowship from the Cancer Institute NSW which led to his return to Sydney.