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Our centre combines clinical and laboratory expertise to tackle autoimmune, inflammatory, and immune deficiency diseases. Starting from a genetic discovery platform, we aim to understand precisely how the immune system goes wrong in each individual patient to cause disease. This approach will make diagnoses more accurate and tailor treatment to each patient. The centre's approach should provide a template for the implementation of genomics and personalized medicine into routine clinical practice
Clonal Evolution In Myelodysplasia And Acute Myeloid Leukaemia Following Azacitidine
Funder
National Health and Medical Research Council
Funding Amount
$853,005.00
Summary
The myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) represent a spectrum of clinically heterogeneous malignancies that remain incurable in the vast majority of patients. Whilst the DNA mutations underpinning the initiation/maintenance of these malignancies are largely known we have little insight into how these mutations alter response to therapy. Using a range of sophisticated cutting edge technologies we will study how these DNA mutations evolve over the course of treatment.
As women age, the quality of their eggs decline and their chance of having a healthy baby plummets. The accumulation of DNA damage within the egg, and the reduced ability to repair this damage, may be one cause of compromised reproductive success in older women. This project will investigate the ability of eggs to repair DNA damage during maternal aging and will explore the importance of DNA repair to fertility and the transmission of high quality genetic material to their offspring.
Examining The Importance Of DNA Damage Repair For Oocyte Quality, Female Fertility And Offspring Health
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
As women age, the quality of their eggs decline and their chance of having a healthy baby plummets. The accumulation of DNA damage within the egg, and the reduced ability to repair this damage, may be one cause of compromised reproductive success in older women. This project will investigate the ability of eggs to repair DNA damage during maternal aging and will explore the importance of DNA repair to fertility and the transmission of high quality genetic material to their offspring.
The Role Of Nuclear Architecture In The DNA Damage Response
Funder
National Health and Medical Research Council
Funding Amount
$561,966.00
Summary
The goal of the proposed research is to understand how dynamic changes to the chromatin genome packaging network, interact with the DNA damage response and gene expression machinery, to repair damaged DNA and the impact this has on cancer biology. To do so we are combining cutting edge molecular biology techniques with innovative novel microscopy methods developed by our research team, that far exceed the spatiotemporal resolution currently used to study chromatin biology.
Improving Oesophageal Adenocarcinoma Outcomes Through Understanding Genomics And Treatment Toxicity.
Funder
National Health and Medical Research Council
Funding Amount
$1,013,282.00
Summary
Oesophageal adenocarcinoma is an aggressive cancer, as most patients will not survive for more than 5 years. Therefore we need to find better ways to treat patients. In this study we will identify the DNA mutations in oesophageal cancers that were part of clinical trial. The data allow us to determine why some tumours responded well to therapy, and why some patients had serious side effects to the treatment. The results will help inform on selection of therapy for future patients.
Identifying Mitochondrial Genome Variants Associated With Familial Migraine Susceptibility
Funder
National Health and Medical Research Council
Funding Amount
$443,273.00
Summary
New therapeutic targets for migraine are desperately needed. Although studies have identified some migraine genes there remains considerable underlying genetic variation to be characterised. This study aims to identify functional variants in the mitochondrial genome that contribute to migraine susceptibility, utilising the isolated Norfolk Island population. Outcomes will determine the significance of the variants identified, potentially leading to new diagnostics.
Identifying Novel Gene Mutations For Molecular Diagnosis Of Familial Hemiplegic Migraine
Funder
National Health and Medical Research Council
Funding Amount
$623,460.00
Summary
This proposal aims to identify novel FHM genes by undertaking an NGS screen of the whole exome of 209 FHM patient samples. We will test the pathological relevance of detected novel mutations by functional analysis in human cell models and using patient-specific stem cell techniques. Using whole genome NGS technology to identify novel mutations will assist in the design and development of a comprehensive NGS approach to diagnose and differentiate this severe neurological disorder.
How Replication Stress Activates The Mitotic Telomere DNA Damage Response To Kill Cancer Cells
Funder
National Health and Medical Research Council
Funding Amount
$486,467.00
Summary
We discovered a novel mechanism linking stress during DNA replication to difficulties with the cell division process, and identified how this turns on DNA damage response signals from the chromosome ends (i.e. “telomeres”). We have further identified that we can exploit this mechanism to kill cancer cells. In this project we will explore this newly discovered mechanism and identify how it can be targeted for therapeutic purposes.
A Functional Assay To Classify Genetic Variants In Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$368,195.00
Summary
At least one person in every 1000 is affected by Lynch syndrome, in which faulty DNA repair machinery causes high rates of cancer. People with Lynch syndrome can have their risk of cancer cut substantially with regular screening. However, we often struggle to understand whether people with 'non-standard' DNA sequences in particular genes actually have Lynch syndrome. This project develops a simple test that will tell clinicians whether a given sequence change relates to Lynch syndrome or not.