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 .
Investigating Post-transcriptional Gene Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
In this program, I will enhance our understanding of cancer gene regulation and provide novel avenues for the treatment of aggressive tumours. Using own data and that from collaborators, I will determine patterns of gene regulation in blood cancers and identify markers that predict disease outcome. I aim to understand how gene regulation can transform healthy cells into tumour cells and whether personalised treatment can kill tumour cells more effectively and prevent relapse and metastasis.
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.
Immunomodulatory Vaccines In The Treatment Of Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$678,899.00
Summary
Peanut allergy is the most common cause of food-induced anaphylactic reactions in Australia and is a major burden to our healthcare system. Current clinical practice advice dietary avoidance to prevent fatal anaphylactic responses. We propose the use of an immunomodulatory vaccine to re-write the immune response to peanut antigens, from an allergic to a tolerant phenotype. This study will provide novel insights into rational approaches for manipulating immune memory to food allergens.
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.