The Structure And Organization Of The Mitochondrial Genome In Health And Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$553,646.00
Summary
Mitochondrial DNA (mtDNA) mutations and mitochondrial dysfunction have been associated with a wide range of multi-system human diseases, although much remains to be learnt about molecular mechanisms in the pathogenesis of these diseases. Our goal is to understand how the expression of the mitochondrial DNA is regulated by mtDNA-binding proteins that will allow us to provide important insights into the molecular mechanisms of mitochondrial diseases.
Targeting Nucleic Acid Synthesis And Cell Division In Gram-negative Bacterial Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$966,800.00
Summary
Some bacteria like Acinetobacter species cause infections in hospitals that are difficult to treat because they have acquired resistance to most antibiotics. This project will combine the complementary expertise of five research groups to develop knowledge of, and how to block, three essential processes in these worrying pathogenic species: copying of DNA, RNA synthesis, and cell division. This promises to lead to development of new antibacterial therapies.
Understanding The Role Of Chromosome Condensation Proteins And Their Link To Disease
Funder
National Health and Medical Research Council
Funding Amount
$601,224.00
Summary
Cells divide through a complex cascade of signals from our genetic material (DNA) which need to be finely tuned for events to occur properly. Errors in control cause faulty cell division and lead to diseases such as cancer. We have identified a master controller of these events termed the condensin complex and aim to understand how it orchestrates these functions by creating a map of its DNA location and understanding which regions in the genetic material it controls and how.
Modelling Epigenomic Change During Early Breast Carcinogenesis Using In Vitro And In Vivo Model Systems
Funder
National Health and Medical Research Council
Funding Amount
$743,360.00
Summary
Epigenetics describes how genes can be turned on and off without a change in the DNA sequence. Epigenetic changes are common and often occur early in cancer, but we do not know where or how epigenetic changes occur in cancer. In this proposal we will create the first detailed map of the epigenetic landscape of normal and cancer breast cells. These maps will allow us to predict where epigenetic lesions occur in breast cancer, which will have important diagnostic and therapeutic value for cancer t ....Epigenetics describes how genes can be turned on and off without a change in the DNA sequence. Epigenetic changes are common and often occur early in cancer, but we do not know where or how epigenetic changes occur in cancer. In this proposal we will create the first detailed map of the epigenetic landscape of normal and cancer breast cells. These maps will allow us to predict where epigenetic lesions occur in breast cancer, which will have important diagnostic and therapeutic value for cancer treatments.Read moreRead less
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.
Understanding And Manipulating Long-range DNA Looping In Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$351,025.00
Summary
The turning on and off of genes often involves physical interactions between the gene and other parts of the DNA that lie far away from the gene. Disruption of this gene regulation is likely to contribute to a wide range of diseases, including heart disease and cancer. This project seeks to better understand the complex puzzle of how the correct DNA connections are chosen over the large number of possible mis-connections, by trying to find the fundamental laws that control DNA-DNA interactions.
Targeting Lagging Strand DNA Replication In Model And Pathogenic Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$590,426.00
Summary
An increasing concern is the growing number of hospital acquired infections that cannot be treated effectively with antibiotics because the bacteria that cause them are resistant to drug treatments. This project will develop our basic understanding of how DNA is copied in bacteria that are about to reproduce themselves, and we will use this knowledge to discover ways to stop them from copying their DNA, thus killing them. This will provide the foundation for development of new antibiotics.
Role Of Epigenetic Modifyers MBD2 And TET Proteins In DNA Methylation And Demethylation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$722,068.00
Summary
Cancer is a disease of both genetics and epigenetics, the cell machinery that controls how the DNA code is read. DNA methylation is one part of epigenetics but few studies have investigated how the loss of methylation contributes to cancer formation. We have exciting new data that implicates specific proteins in this process and, with this funding we will determine how these proteins affect gene regulation in cancer, potentially leading to novel cancer diagnosis and treatment strategies.
Four Dimensional Epigenome Remodelling: Implications For Endocrine Resistance In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$828,560.00
Summary
Patients with estrogen receptor positive breast cancer receive endocrine therapy, however half fail to respond and relapse. Endocrine resistant breast cancer currently represents the most significant challenge to breast cancer treatment. We suggest that three-dimensional epigenetic remodelling is an underlying mechanism that determines endocrine sensitivity that we will exploit as a novel therapeutic strategy to effectively treat patents with recurrent disease.
DNA METHYLATION And DEMETHYLATION IMBALANCE In CANCER
Funder
National Health and Medical Research Council
Funding Amount
$635,443.00
Summary
This study will give us new insights into the role of MBD2 and TET proteins in establishing the epigenome and especially will have a major impact in our understanding of the key steps involved in both de novo DNA methylation and demethylation in cancer. Ultimately these new understandings may provide routes to use MBD2 and/or TET proteins as pharmacological targets in cancer treatment.