Cancer and genomics

Prostate cancer research in Tasmania

Prostate cancer is the second-most diagnosed cancer in Australia after non-melanoma skin cancer.

An important risk factor is family history. Our team has developed a unique prostate cancer resource comprising genetic samples, and clinical and treatment information.

A strength of our resource is the inclusion of samples from large Tasmanian families with multiple cases of prostate cancer. We use a range of recently developed ‘omics’ technologies to look at inherited genetic factors, and other molecular changes in the tumours themselves, to better understand this disease.

We have been able to identify carriers of high-risk genes associated with prostate cancer and provide feedback about these results to our participants. We have also identified factors that underpin aggressive tumours. Building this understanding will help us to develop much-needed gene-based tools to improve diagnosis, prognosis, and treatment options for men.

The MS family sequencing study

MS is a complex multifactorial disease, and our genes play an important part in determining who is at risk. By comparing the genomes of people with MS to those without, we are identifying the genetic changes that predispose to developing MS.

We are focusing on families with multiple members affected by MS, as they show enrichment for the genetic causes, making them easier to find. We are also combining genomic information from unrelated people with MS with other types of biological information from blood and brain cells as well as clinical and environmental information. By mapping these complex interactions, we can pinpoint which ones are disrupted in MS.

Predicting and preventing glaucoma through genetics

Glaucoma is the leading cause of permanent blindness globally and is one of the most inheritable human diseases. Timely intervention is critical and can now prevent vision loss, but current screening approaches are not cost-efficient.

Using gene-based risk profiling from two decades of research, we have developed a polygenic risk score for glaucoma. It outperforms current prediction tools and confers higher predictability than for any other common, complex disease. Using this score we have shown we can predict disease progression in early stages of glaucoma, predict the need for and intensity of treatment, and predict the likelihood that surgery will be required later. We have also shown that the implications of our work extend beyond European ancestry by demonstrating utility in South Asian populations.

In ongoing work, we are employing a ‘precision medicine’ approach to establish a world-first trial using both clinical and genetic measures of glaucoma risk to determine the accuracy of our polygenic risk score.

The genetics of childhood cataract

Infant and childhood cataract can lead to lifelong visual impairment or blindness. As many childhood cataracts are inherited, we work with families nationwide to identify the genes that lead to them.

Using whole genome sequencing, we hone in on the genetic differences between family members with and without cataract. When we find a new gene, we can alter it in zebrafish to prove that it causes cataract. Zebrafish share 70% of their genes with humans.

Over the last 20 years, our findings have helped hundreds of patients, enabling earlier diagnosis and improved genetic testing for this disease in affected families. We recently discovered a new gene called PGRMC1 that, when ‘deleted’, causes cataract in boys. Women who carry the same mutation can pass it on to their sons.

Taking immunology back to nature

While new vaccines and treatments are usually trialled in laboratory animals, we study cancer and other diseases in wild species. We lead an international Wild and Comparative Immunology consortium that aims to expand understanding of how genetics and the environment affect the immune system of different species.

While our focus is developing a vaccine against transmissible cancer in Tasmanian devils, our work also informs the development of better vaccines and immunotherapies for humans and other species, including dogs. Our team has also contributed to an industry-sponsored project to develop a portable detector for SARS-CoV-2 and other viruses.

Devil Facial Tumour Disease

The Tasmanian Devil is under threat of extinction by a contagious cancer called Devil facial tumour disease (DFTD), an aggressive non-viral, transmittable parasitic cancer. Small lesions or lumps, in and around the mouth, quickly develop into large tumours on the face and neck (and sometimes other parts of the body). The tumours interfere with feeding and the affected animal may starve to death. Once the cancer becomes visible, it is almost always fatal. It is estimated the Tasmanian devil population has declined by as much as 50 per cent since the onslaught of the disease, and has affected devil populations in 65 per cent of Tasmania, with concentrations highest across the eastern part of the state. Menzies researchers are investigating treatments for the prevention of DFTD.

This is a unique situation as cancer is not contagious but this tumour is transmitted between devils through biting. Because the tumour is passed between devils it suggests there is something wrong with the immune system of the devil. However, our studies have clearly shown the Tasmanian Devil has a healthy immune response. By performing studies on lymphocytes from devils around the state, we have good evidence to indicate there is limited genetic diversity among the Devil population hence the tumour is not recognised and eliminated by the immune system. Our immediate aim is to determine how we can encourage the Devil's immune system to recognise and destroy the tumour. We are also screening wild devils to determine if any Devils in the wild might be naturally resistant to Devil facial tumour disease. The tumour itself is also unique so studies are underway to understand the unique features of this mysterious cancer.

We determined that the Tasmanian Devil has a competent immune response and that the transmission between devils is most likely due to a lack of genetic diversity. West Coast Devils have a much greater diversity than the diseased East Coast and we immunised two Tasmanian Devils with irradiated DFTD tumour cells. One of these devils responded to the immunisation and when challenged with live tumour cells, resisted the disease. Hence it might be possible to protect some devils by vaccinating. Mixed lymphocyte reactions among eastern and western devils were performed, and some experiments (especially between West vs East Devils) showed high reactions, supporting the evidence for increased genetic diversity in the western population.

Marrow Map: Bone Marrow Failure Syndromes genetic research

Bone Marrow Failure Syndromes (BMFS) are a group of diseases that cause the bone marrow stem cells to reduce or stop the production of healthy red blood cells, white blood cells and platelets needed by the body. Currently, very little is known about its genetic causes, and treatment options are limited.

In ongoing research, we aim to genetically map and functionally characterise genomic influences on blood cell homeostasis. We aim to profile circulating blood cells from a large, population-based cohort of people living in Tasmania.

The insight from this work will lead to the development of novel markers for disease profiling and the identification of potential therapeutic targets for BMFS.

This study is currently open for volunteers. Find out more and how to get involved at Join a study.