Research Theme

Genetics

Many cancers are caused by an inherited, or genetic, tendency that interacts with other factors to result in the onset of the cancer. The identification of the genes underlying many diseases has led to both a greater understanding of the disease and, in some cases, significant advances in treatment therapies.

Some examples of research projects within the Genetics research theme at the Menzies Research Institute:

Tasmanian Genetics Study of Haematopoietic Malignancies

Leukaemia, lymphoma and myeloma are cancers of blood cells (haematological malignancies). These affect both children and adults, with over 6,400 cases diagnosed each year in Australia. Therapies and survival rates have improved, however treatments such as chemotherapy and bone marrow transplantation are associated with considerable morbidity and mortality and there remains an urgent need to understand the underlying causes of these haematological cancers. There is strong evidence for an underlying genetic predisposition to these cancers, with a triggering event (genetic or environmental) that results in the manifestation of the cancer. Elucidation of the genes predisposing individuals to developing these cancers will assist in understanding the process of development of disease, reveal new strategies for treatment and the development of treatment regimes based on genetic phenotype.  Knowledge of susceptibility genes will also help us understand how environmental risk factors may interact with these identified genes to influence risk of disease and disease course.

More than 200 families with multiple cases of haematological malignancies have been identified and eleven very large families have been prioritised for immediate recruitment, and sample collection for further study. Of particular interest is one large family and samples have been collected from affected and unaffected relatives for this priority family for analysis.  Cutting edge technology using the Affymetrix HMA250K SNPchip platform available at the Australian Genome Research Facility has been used to generate genetic profiles for these individuals. Analysis is underway to identify genomic regions of interest which are likely to be relevant to development of disease.

Prostate Cancer Case Control study in Tasmania (Tascap)

The aim of this study is to examine the genes mediating the physiological response to sun exposure and how they may interact with environmental factors to modify prostate cancer risk. This project is a continuation of the previous project titled Case Control Study of Prostate Cancer in Tasmanian Men. Preliminary data collection and analysis revealed some interesting findings relating sun exposure to prostate cancer risk. The funding provided by the Department of Veterans’ Affairs supports the expansion of the number of participants in the study. Achieving the target number of 800 participants will facilitate the meaningful identification of modifiable environmental factors which may interact with genetic factors to influence prostate cancer risk.

The Tasmanian Familial Prostate Cancer Genetics Study

Every year around 11 000 Australian men are diagnosed with prostate cancer and more than 2500 die, making prostate cancer the second largest cause of male cancer related death. Current therapies are associated with significant side-effects and whilst improvement in survival and prognosis is achieved when disease remains confined to the prostate, there is little understanding of the factors influencing disease progression. There remains a great need improve our understanding of the contributing factors determining onset and progression of prostate cancer through the elucidation of the underlying genes causing disease.  Our study aims to identify those genes which predispose individuals to developing prostate cancer and also those genes contributing to progression of this disease.

The study of families with multiple cases of prostate cancer is a powerful approach used to identify the genes that cause disease.  Our team has developed a rare dataset comprising a number of such families. An in depth examination of the genetic profiles of individuals with and without prostate cancer has been conducted. This analysis has identified interesting genetic regions, including one on chromosome 5p and very recently a gene has been identified in this region which is significantly associated with prostate cancer risk.
Further work designed to gain a better understanding the processes involved in prostate cancer progression is also being undertaken.  An in-depth examination of genetic changes in prostate cancer tumours has revealed that common patterns of genetic changes are observed in a number of patients from the same family.  Few, if any, studies world-wide have examined genetic changes in prostate cancer tumours in such a large number of individuals from a single family. 

The role of platelets in malaria infections

We have evidence from work with mice that animals with low platelet counts are susceptible to malaria infection. Aspirin, which is a platelet inhibitor, also renders a resistant animal more susceptible. We are currently translating our findings in mice to human cases of malaria. We have found that purified human platelets have the ability to inhibit the growth of human malarial parasites (Plasmodium falciparum) in culture.

Finding suppressor mutations for epilepsy

In this project we are looking for genetic mutations in mice which have the ability to reverse the activity of kainic acid, an organic compound which causes seizures. Proteins produced by the genes carrying these mutations will potentially be targets for new epilepsy therapies. We have identified four types of mice that are more resistant to the seizure activity of kainic acid. We are now taking the next step to identify the region of the genome which is carrying the mutation.

Identifying host targets for novel antimalarial therapy using an ENU suppressor screen

We believe that a new anti-malarial drug strategy which targets host molecules has many advantages over the current anti-parasite drugs. These drugs will hinder the development of resistance by the parasite. We are identifying potential drug targets using a technique known as an ENU mutagenesis suppressor screen.

Identifying host targets for novel antimalarial therapy using a bioinformatics approach

This project is also investigating the potential of a new drug strategy to target host molecules rather than the malaria parasite itself. We are identifying potential drug targets using the genome sequences of both humans and the parasite to find genes which are likely to present as host targets. This project has just begun and some early targets are being tested. Inhibitors for these proteins are being tested in cultured P. falciparum.

For more information, contact:

 

Professor Simon Foote

Director

Telephone: (03) 6226 7702