Local Sleep In The Awake Brain: An Underlying Cause Of Neurobehavioural Deficits In Sleep Apnea?
Funder
National Health and Medical Research Council
Funding Amount
$582,330.00
Summary
Obstructive sleep apnea (OSA) is a common sleep disorder which significantly impacts daytime functioning leading to excessive sleepiness, and problems with attention and thinking. Currently, the causes for cognitive impairment in OSA (including attentional lapses and performance deficits) are poorly understood. In the awake state, groups of neurons can briefly go “offline” as they do in sleep. These periods of “local sleep” may explain impaired task performance in OSA.
Vascular And Neurogenic Determinants Of Hypertension In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$508,142.00
Summary
You are as old as your arteries, and people with kidney disease have arteries that age fast. They also have overactive sympathetic nerves, and it is not clear if the blood vessels or nerves are responsible for the high blood pressure that puts strain on the heart and other organs of these patients. We will use an animal model to determine if therapy for hypertension reduces the stiffness of blood vessels or elevated nerve activity. Our results will enable better treatments for kidney failure.
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
H2A.Z Acetylation: Deregulation Of Enhancer Activity And 3D Chromatin In Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$859,350.00
Summary
DNA is not linear but packaged in the cell nucleus in a three-dimensional (3D) structure in such a way that distal regulatory regions can interact to control gene expression. Our new data suggests that a chemical modification of the histone variant H2A.Z plays a critical role in the formation of the 3D chromatin structure. This project is aimed to dissect the role of H2A.Z in prescribing 3D structure, which will provide a more precise understanding of gene deregulation in cancer.
Deciphering The Transcriptional Program That Instructs Lymphatic Endothelial Cell Fate.
Funder
National Health and Medical Research Council
Funding Amount
$541,950.00
Summary
Lymphatic vessels are essential to maintain fluid balance in most tissues of the human body. Further the lymphatic vasculature plays a central role during cancer and contributes to tumour metastasis. Despite this integral function in health and disease little is known about the molecular programs that coordinate gene expression to build a functional vasculature. This research project will address this gap in our knowledge and will open up new therapeutic avenues for lymphatic vascular disorders
Regulation Of Ribosomal RNA Gene Chromatin During Malignant Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$882,486.00
Summary
The overarching goal of this proposal is to determine the molecular basis for tumour cell dependence on activated ribosomal RNA gene repeats (rDNA). Our working model posits that rDNA repeats become activated through changes in rDNA chromatin structure that include increased binding of the RNA Polymerase I transcription factor UBF.
Mechanistic And Functional Analysis Of The Id4 Proto-oncogene In Breast And Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$693,983.00
Summary
Cancer arises through damage to normal regulatory processes in cells. Understanding these damaged processes is essential to implement personalized medicine. This proposal explores the role of the proto-oncogene ID4 in the closely related cancers triple negative breast cancer and serous ovarian cancer. This research may lead to the development of new therapeutic strategies or the refinement of existing strategies for these poor prognosis cancers.
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 The Mechanisms For Ameliorating/preventing Antipsychotic-induced Obesity In Early Life
Funder
National Health and Medical Research Council
Funding Amount
$576,496.00
Summary
There has been a sharp worldwide increase during the last decade in antipsychotic prescriptions (mostly “off-label”) to paediatric patients. One important issue is that antipsychotic drugs were developed for adult patients and normally have serious side-effects. This project will not only reveal the mechanisms of antipsychotic-induced obesity side-effects in youth, but will also explore intervention strategies for preventing antipsychotic-induced weight gain/obesity in paediatric patients.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.