Ligand Interactions Of The MC1R Receptor And Cellular Consequences For Melanocyte Responses To UV-damage
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
Although it is evident that fair skin types are more susceptible to sun damage, the relationship between sun exposure, skin colour and skin cancer formation is less clear. The genes and processes that determine an individual's skin phototype and the mechanisms involved in the tanning response after UV-exposure of the skin are the focus of this investigation. A major regulator of the response to UV radiation in the skin is the melanocortin-1 receptor. It is essential to understand the complex int ....Although it is evident that fair skin types are more susceptible to sun damage, the relationship between sun exposure, skin colour and skin cancer formation is less clear. The genes and processes that determine an individual's skin phototype and the mechanisms involved in the tanning response after UV-exposure of the skin are the focus of this investigation. A major regulator of the response to UV radiation in the skin is the melanocortin-1 receptor. It is essential to understand the complex interactions of this receptor that induce tanning.Read moreRead less
Diabetes is a major health epidemic; and both type 1 and type 2 diabetes can lead to the development of diabetic complications - the major cause of morbidity and mortality from diabetes. Loss of islet function is a key factor in diabetes and my testable hypothesis is that islet inflammation contributes to this process. We will investigate how genes effect islet inflammation. New understanding could lead to biomarkers for determining who is susceptible & new treatment opportunities.
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.
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.
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.
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.
Understanding The Role Of SSB1 In Embryonic Development And Genome Maintenance
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
Normally DNA exists as a double helix where two strands are zipped together. When single-stranded (ss) DNA is exposed during various cellular processes it can be easily damaged and degraded by cellular enzymes, but is protected by ssDNA binding proteins (SSBs). We have identified two new SSBs (SSB1 and SSB2) that play a crucial role in DNA repair and will investigate the role and physiological function of these important proteins.
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.
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.