Deciphering Mechanisms Of Disease Evolution In Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$845,093.00
Summary
In many patients, cancers are ever-changing, even after they have formed. This explains why many cancers can spread beyond the point of cure by surgery and why they can become resistant to treatments. This project will use patient melanomas and laboratory modelling to understand how melanomas change as they grow and spread. The results will be used to identify the nature of evolutionary changes in cancer in order to predict and even exploit them in treatment.
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
Exposing The Mechanisms Underlying Mammalian Meiotic Onset
Funder
National Health and Medical Research Council
Funding Amount
$536,563.00
Summary
Germ cells must undergo a special form of cell division, meiosis, before they can form oocytes in females or sperm in males. We want to know, in detail, how meiosis is triggered in germ cells and what the first steps are in meiotic progression. This information will help us understand the causative factors in infertility (1 in 6 couples of reproductive age are infertile), control fertility (develop new contraceptives) and avoid testicular cancer (the most common tumour type in young men).
Improving The Phenotypic Severity Of Intellectual Disability And Seizures Caused By Expanded Polyalanine Tract Mutations In The ARX Homeobox Transcription Factor.
Funder
National Health and Medical Research Council
Funding Amount
$683,622.00
Summary
Intellectual disability is frequent in the population, with as many as 1 in every 50 people in the world directly affected. ARX is a gene mutated in X chromosome-linked intellectual disability and seizures. Our study will comprehensively address the basis for improvements to disease outcomes following treatment with steriod horomones in mice modelling these mutations. We will also address the mechanism contributing to disturbed protein function due to these expanded polyalanine tract mutations.
Characterization Of HOXA-expressing Human Haematopoietic Cells Generated From Embryonic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$622,464.00
Summary
Blood stem cell transplants are used for treating a range of human blood disorders such as leukaemias. However, for many patients, suitable donors cannot be found. We are searching for ways in which embryonic stem cells can be turned into blood stem cells in the laboratory to provide a new source of these cells that could then be used to treat patients.
The Role Of The Homeobox Transcription Factor Hhex In Haematopoiesis And Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$623,112.00
Summary
We have shown that the Haematopoietically expressed homeobox (Hhex) protein plays important roles in development of immune cells. In addition, Hhex is required for development and maintenance of Acute Myeloid Leukemia (AML). This project will further investigate the requirement of Hhex in human AML, potentially identifying a new therapeutic target in this poor-prognosis cancer subtype. In addition, we will identify critical cofactors and targets of Hhex, revealing new therapeutic strategies.
Understanding The Causes Of Childhood Congenital Anomalies Of The Kidney And Urinary Tract
Funder
National Health and Medical Research Council
Funding Amount
$609,748.00
Summary
Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified ....Congenital anomalies of the kidney and urinary tract (CAKUT) is a common cause of renal failure in children. The majority of patients with CAKUT do not know the underlying cause of their renal anomalies. In this proposal we will characterise the developmental events that are perturbed in three mouse models of CAKUT and identify the causal gene responsible in each mouse model. We will translate this information to the clinic by screening patients with CAKUT for mutations in these newly identified genes.Read moreRead less
Investigating Tumour Initiation And Growth In A Panel Of Mice Defective In Epigenetic Reprogramming.
Funder
National Health and Medical Research Council
Funding Amount
$421,600.00
Summary
Until recently it was believed that cancer is always caused by mutations in genes. Now it has been proposed that chemical modifications to the DNA and the proteins that package the DNA may also initiate cancer. These "epigenetic" modifications control whether our genes are switched on or off. Epigenetic modifications are disrupted in cancer, but it is not known whether they can start tumour growth. I will study this using mouse models. This work may lead to preventative screening and new treatme ....Until recently it was believed that cancer is always caused by mutations in genes. Now it has been proposed that chemical modifications to the DNA and the proteins that package the DNA may also initiate cancer. These "epigenetic" modifications control whether our genes are switched on or off. Epigenetic modifications are disrupted in cancer, but it is not known whether they can start tumour growth. I will study this using mouse models. This work may lead to preventative screening and new treatments in humans.Read moreRead less
How Does Genetic Variation For Trig Affect Autoimmune Responses Mediated By Toll-like Receptors?
Funder
National Health and Medical Research Council
Funding Amount
$671,114.00
Summary
Juvenile diabetes is an autoimmune disease that affects more than 120,000 Australians. We have recently discovered a novel gene, named Trig, in a genetic study of mice that develop juvenile diabetes similar to children. This research proposal aims to determine the function of Trig in the immune system and how it contributes to the development of autoimmune diseases, such as juvenile diabetes.
A Genomic Approach Towards An Understanding Of Clonal Evolution And Disease Progression In Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$671,689.00
Summary
Cancer development is associated with changes in the genetic composition of the cell. These changes involve the loss/gain of genetic material and/or changes in gene expression. Using sophisticated technology, we will define the changes in the genes that are associated with the transition from a benign to a malignant cancer state. We will examine this process in the blood cancer, multiple myeloma, in order to identify new treatment targets for this incurable disease.