Brain Connectivity Imaging Markers To Confirm Diagnosis For Bipolar Vs. Unipolar Depression – A Connectome Approach.
Funder
National Health and Medical Research Council
Funding Amount
$434,369.00
Summary
Differentiating Bipolar disorders from Unipolar Depression is a major clinical challenge. This misdiagnosis hinders optimal clinical care and has many deleterious consequences such self-harm, increased chances of suicide, poor prognosis, and greater health care costs related to this disorder. This project will provide urgently-needed advance in accurate identification of Bipolar disorders using Magnetic Resonance Imaging and remove one of the key obstacles to accurate diagnosis.
Developmental Schizotypy In The General Population: Early Risk Factors And Predictive Utility.
Funder
National Health and Medical Research Council
Funding Amount
$830,952.00
Summary
This study will determine early childhood risk factors for psychosis-proneness in children aged 11 years, and emerging signs and symptoms of mental health disorders of these children, using population data from the NSW Child Development Study. Determining risk for psychosis as early as possible in the life course will enable the provision of preventative interventions to children at critical points in development.
The Biology Of Risk For Bipolar Disorder: Genetic Effects In A High-risk Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$856,412.00
Summary
Bipolar disorder is a severe mood disorder affecting over 350,000 Australians. Some children of bipolar disorder patients will also become ill, although currently we have no tools to predict which of these genetically at-risk young individuals will eventually develop symptoms. This study will use genetic information plus brain structural changes to predict which at-risk individuals are likely to become ill. This study will help elucidate early clinical and biological markers of bipolar disorder.
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.
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.
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.
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.
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.
The Structural Basis For Promiscuity Of Drug Binding To HERG K+ Channels
Funder
National Health and Medical Research Council
Funding Amount
$713,035.00
Summary
Special proteins called ion channels control the electrical activity of the heart. Drugs that block ion channels can have the unwanted side-effect of altering the rhythm of the heart beat and causing sudden cardiac death. Extensive efforts are made to screen for this problem during drug development but it is still an inexact science. Here we will use high resolution imaging technologies to get a better understanding of how drugs bind to ion channel proteins.