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.
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.
Cluster Randomised Trial Comparing One Versus Two Doses Of Ivermectin For Mass Drug Administration To Control Scabies
Funder
National Health and Medical Research Council
Funding Amount
$540,512.00
Summary
Scabies is a common skin disease in developing countries, in particular in the Pacific region. In the Western Province of Solomon Islands, one in two children suffer from the infestation, and 20% of the population. We know that mass drug administration with two doses of oral ivermectin is effective to reduce the burden of scabies in the community. We now propose a study to determine whether one single dose is as effective. This would have major public health benefits.
Does Mass Drug Administration For Scabies Result In Control Of Serious Bacterial Complications? A Proof Of Concept Towards Global Elimination.
Funder
National Health and Medical Research Council
Funding Amount
$883,760.00
Summary
Scabies is common skin disease in developing countries, in particular in the Pacific region. In Fiji, one in two children suffer from the infestation, which affects over 20% of the population. A recent study conducted in Fiji on 2000 people showed that mass drug administration (MDA) with oral ivermectin is a safe and effective way to reduce the burden of scabies in the community. We will expand the MDA program to 100,000 people, the largest study of MDA ivermectin for scabies ever undertaken.
Deciphering The Role Of Atypical DNA Methylation In Neuronal Genome Regulation And Neurological Disorders
Funder
National Health and Medical Research Council
Funding Amount
$773,484.00
Summary
This research will use a combination of genomic, biochemical and functional genomics approaches to investigate the role of the atypical mCH form of DNA methylation in neuronal genome regulation and function, and provide new insights into the role of the epigenome in healthy brain function and neural pathologies.
Optimising Large-scale Public Health Interventions To Control Neglected Tropical Diseases
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Neglected tropical diseases (NTD) are a group of health conditions that affect the poorest of the poor, particularly in remote and rural areas. They affect the most vulnerable communities and cause substantial, chronic health harms impairing personal and social development. Several debilitating NTD are common in remote indigenous communities and Pacific islands. I propose a series of studies to investigate new strategies to control NTD in large populations where these diseases are endemic.
Epigenetic Changes In The Prostate Cancer Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$848,954.00
Summary
Many men with prostate cancer have slow-growing tumours that are unlikely to spread outside the prostate. These men with low-risk cancer are often monitored to prevent unnecessary aggressive treatments. However, the current methods used to distinguish between slow-growing and aggressive tumours are imprecise and there is a risk of missing aggressive tumours. We aim to identify new biomarkers of prostate cancer by measuring modifications to the DNA in the tumour and surrounding cells
Circulating Tumour DNA To Monitor Treatment Response And Resistance In Chronic Lymphocytic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$876,950.00
Summary
Many cancers shed small amounts of DNA (ctDNA) into the patient’s bloodstream and recent advances in genomic technologies now allow levels of ctDNA to be accurately measured in the blood. Changes in ctDNA levels have potential to be used as specific markers of disease progression and/or response to cancer therapy. This project will evaluate if ctDNA can be used to monitor treatment responses and individualise treatment decisions in patients with chronic lymphocytic leukaemia.
Horizontal And Vertical Transmission Mechanisms Of Staphylococcus Aureus Multiresistance Plasmids
Funder
National Health and Medical Research Council
Funding Amount
$408,993.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of serious hospital-acquired, and increasingly community-acquired, infections. The bacteria have mechanisms that cause efficient transmission of resistance genes to their offspring as well as to other strains. This project aims to elucidate key features of these mechanisms so that treatments can be devised that disrupt the maintenance and transfer of resistance, so as to prolong the effectiveness of antibiotics.
CTCF is a unique architectural protein that regulates the three-dimensional (3D) folding of the genome to switch our genes on, or off. This is important, as it affects how DNA is arranged inside the cells, which is turn assures correct gene expression patterns. Here, we will define the role of CTCF in organizing the 3D genome architecture and identify genetic and epigenetic states that control its function.