Integrating Immunity And Genetics In Follicular Lymphoma To Establish A Prognostic Score Fit For The Modern Era
Funder
National Health and Medical Research Council
Funding Amount
$1,377,174.00
Summary
Follicular lymphoma (FL) is divided into early and advanced stages. Early stage FL is frequently cured, but there is no way to identify who will be cured and who won't. By contrast advanced stage FL is incurable. Our unique access to well-annotated clinical trial and population based cohorts allows us to perform a detailed biological comparison of early and advanced FL, to gain a deeper understanding of the impediments to eradicating the disease, and to predict outcome to conventional therapy.
Self-destructing CRISPR-constructs For Targeted Genome Editing In The Retina.
Funder
National Health and Medical Research Council
Funding Amount
$679,926.00
Summary
Despite the identification of specific mutations causing many inherited retinal dystrophies, all of these conditions are currently untreatable. We have established gene-editing techniques and have developed a novel mouse model, which will serve as a robust platform for testing different techniques of gene editing in the retina. No other group in the world is known to be using this platform for gene editing and our work will expedite the clinical translation of this technology.
Identification Of Protein Altering Variants Influencing Preeclampsia Risk
Funder
National Health and Medical Research Council
Funding Amount
$572,014.00
Summary
Preeclampsia is a common and serious pregnancy disorder for which there is currently no early diagnostic test or cure other than delivery. It is also associated with later life cardiovascular disease. The identification of gene mutations for preeclampsia in this study will provide insight into the cause of this disorder that may lead to new treatments and tests to predict those women at risk.
Identification Of Novel Familial Patterns And Genotypes Associated With Inherited Risk In Adult-onset Sarcoma: The International Sarcoma Kindred Study
Funder
National Health and Medical Research Council
Funding Amount
$552,855.00
Summary
Inherited genetic risk is important in cancers that affect the young. The International Sarcoma Kindred Study (ISKS) is the world's first prospective study aiming to better understand how sarcomas can be inherited in families, and the genes that cause sarcomas. The ISKS is a multinational study led from Australia, with partners in the US, Europe and India, and aims to recruit over 3000 families affected by sarcoma.
Fractures And Bisphosphonates: Reviving Osteoporosis Treatment Uptake By Identifying The Genetic, Material, And Microstructural Risk Factors Of Atypical Femur Fractures.
Funder
National Health and Medical Research Council
Funding Amount
$1,053,094.00
Summary
Atypical femoral fractures (AFF) are uncommon, but catastrophic, complications of antiresorptive osteoporosis treatments including bisphosphonates. We will identify patients at risk of AFF by determining changes in their bone structure and quality, and identifying genes that increase the risk of these fractures. In this way, cheap and effective antiresorptive treatments can be targeted to patients at the lowest risk of AFF and alternative treatments to those at highest risk.
BRCA-P: An International Randomised Phase III Study Evaluating The RANK Ligand Inhibitor Denosumab For The Prevention Of Breast Cancer In BRCA1 Mutation Carriers
Funder
National Health and Medical Research Council
Funding Amount
$2,589,049.00
Summary
Women with a faulty BRCA1 gene are at high lifetime risk for breast cancer. Identifying a safe and effective prevention therapy is therefore a ‘holy grail’. We have discovered that denosumab, used to treat osteoporosis or breast cancer spread to bone, could be ‘repurposed’ as a prevention drug. BRCA-P is an international randomised controlled study that will determine if denosumab prevents breast cancer. Associated translational research will facilitate swift transfer to the clinic.
Using Artificial Synapses To Investigate The Functional Pathology Underlying Epilepsy
Funder
National Health and Medical Research Council
Funding Amount
$515,256.00
Summary
Epilepsy is a common neurological disorder. Some forms arise from hereditary mutations to GABA-A receptors. To advance our understanding of epileptogenesis, it is necessary to understand how mutations affect GABA-AR function. We will use a novel ‘artificial synapse’ system to characterise these mutant receptors. This will define how epilepsy is caused and inform us how to best tailor drug treatments for different epilepsy conditions.
Impact Of Aberrant Branchpoint Selection In Myelodysplasia And Chronic Lymphocytic Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$605,326.00
Summary
Most human genes are spliced together from smaller exon parts. CIA Mercer has found that if splicing proceeds incorrectly backwards, small circular RNAs and incomplete genes are built. The splicing machinery responsible for this process is recurrently mutated in blood disorders, notably Myelodysplasia and Chronic Lymphocytic Leukaemia. We propose that these mutations cause backwards splicing of key genes responsible for these disorders, representing a major new pathway to cancer.
Genetic Analysis Of De Novo And Inherited Exome Variation In Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$1,351,522.00
Summary
Schizophrenia (SCZ) is a severe mental disorder affecting ~1% of the world’s population. The majority of risk is explained by genetic factors, and thus identifying susceptibility genes may lead to the development of novel therapeutics and personalised treatments. We will join forces with international collaborators to perform the largest DNA sequencing analysis of de novo and inherited protein-coding sequence variation in SCZ to date. We aim to identify key risk genes and genetic pathways.
Genetic Analysis Of The Relationship Between Parental Age And Risk Of Psychiatric Disorders
Funder
National Health and Medical Research Council
Funding Amount
$301,012.00
Summary
Age-related de novo mutations are widely assumed to explain the association between advanced paternal age and risk of psychiatric illness, but this mechanism cannot explain the known risk to offspring of teenaged parents. We will investigate an alternative hypothesis for risk to children due to parental age, which is that elevated liability to mental illness, arising from shared genetic factors between parents and offspring, leads to delayed, or conversely teenage, parenthood.