Understanding The Function Of Recql4 In DNA Replication And Genome Maintenance
Funder
National Health and Medical Research Council
Funding Amount
$698,447.00
Summary
We are interested in understanding how cancer forms. We are using information from human cancers to understand how a protein causes cancer. We are using models to understand how mutations in this protein give rise to bone cancer. These models are used together with detailed biochemistry to understand how the mutations affect protein function.
A Tumour Suppressor Pathway That Removes DNA-RNA Hybrids
Funder
National Health and Medical Research Council
Funding Amount
$935,780.00
Summary
DNA:RNA hybrids are found normally in our chromosomes. But, the regions where DNA:RNA hybrids form are linked to chromosome changes that occur during breast and blood cancer development. We have uncovered why these chromosome changes occur, and have linked it to the important function of a cancer-associated gene called FANCM. Our study is exploring this important finding that has implications for both the cause and treatment of cancer.
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.
Telomere Structural Abnormalities In Cells Using Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$522,122.00
Summary
The continuing growth of cancers depends on their cells being able to prevent shortening of chromosome ends (telomeres). Some cancers, including very aggressive brain and connective tissue tumours, achieve this via the Alternative Lengthening of Telomeres (ALT) process. We have evidence that the telomere structure of normal cells prevents ALT. Here we will examine how the telomere structure of ALT-positive cancer cells is changed, and whether reversing these changes inhibits ALT.
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.
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.
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.
Wolbachia And West Nile Virus In Mosquitoes: Friends Or Foes?
Funder
National Health and Medical Research Council
Funding Amount
$561,028.00
Summary
Mosquito-borne viruses pose a great risk to human and animal health. Presence of compentent vectors of several viruses in Australia indicates vulnerability of Australia’s biosecurity. This project will define the mechanisms of inhibition of virus replication in mosquitoes by a symbiotic bacterium which can be utilized in virus inhibition.
Architecture Of The Hendra Virus Nucleocapsid And Implications For Replication
Funder
National Health and Medical Research Council
Funding Amount
$342,108.00
Summary
Hendra virus causes sporadic fatal outbreaks in horses, which may result in human deaths through direct contact with infected animals. The unanticipated surge of Hendra cases since mid-2011, the broad host range of the virus and the discovery of other related viruses worldwide highlight the epidemic potential of hendra-related paramyxoviruses. To improve our preparedness against paramyxoviruses, this Project aims at determining the structure of the viral replication machinery.
Role Of Flavivirus-encoded Small Regulatory RNAs In Virus-mosquito Vector Interactions
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
Mosquito-borne diseases are major threats to human health. MicroRNAs are small non-coding ribonucleic acids (RNAs) that play important roles in development, cancer, apoptosis, immunity, longevity, and viral infections. We propose to identify the regulatory microRNAs from flaviviruses and establish their potential function in vector-arboviruses interactions. The project will put Australia at the forefront of research in the most rapidly developing area of microRNA research.