The adult heart has an extremely limited capacity for regeneration. In contrast, I recently discovered that the newborn heart can completely regenerate following a heart attack. How and why the heart loses this regenerative capacity after birth is not known. This Fellowship aims to unravel the genetic circuits that govern cardiac regenerative capacity. The proposed research program will develop novel therapies for heart regeneration through molecular targeting of regulatory RNA molecules.
The Role Of Ikaros In Establishing Regulatory Networks For Lymphocyte Development
Funder
National Health and Medical Research Council
Funding Amount
$345,809.00
Summary
Ikaros is a protein that regulates gene expression during development of lymphocytes from blood stem cells. Ikaros has a profound importance in normal and malignant lymphocyte development, but we still do not know how it controls these processes. The aim of my study is to identify genes regulated by Ikaros and the molecular mechanisms of their regulation. This study will contribute to understanding of the regulatory network controlling the development and function of lymphocytes.
Defining The Role Of A Novel Transcriptional Enhancer Element In Regulation Of Prox1 Expression And Endothelial Cell Identity.
Funder
National Health and Medical Research Council
Funding Amount
$706,909.00
Summary
The precise spatial and temporal control of gene expression is regulated by non-coding regions of the genome termed enhancers. Enhancers are crucial to program cell identity and have established roles in development and disease. We have identified a novel enhancer that we hypothesise controls the identity of valve endothelial cells by regulating expression of a master programmer of lymphatic endothelial cell identity, PROX1. Here we will investigate the role of this enhancer during development.
An Alternate Function Of The MicroRNA Biogenesis Machinery
Funder
National Health and Medical Research Council
Funding Amount
$302,981.00
Summary
Controlling the activity of genes is crucial. Too much or too little can result in a cell not functioning properly. We have discovered a new way genes are controlled. We have found that an enzyme called Drosha can prevent too much activation of some genes by chopping up the products of these genes. This way of controlling genes appears to be especially important for developmental processes, such as occurs in the embryo. Our goal is to understand this mechanism precisely at the molecular level.
Investigation Of Processed SnoRNAs As Cryptic Regulators Of The Imprinted Prader-Willi Syndrome Locus
Funder
National Health and Medical Research Council
Funding Amount
$673,976.00
Summary
Prader-Willi syndrome (PWS) is a devastating disorder whose symptoms include intellectual disability and compulsive eating. PWS occurs when a piece of the genome is mistakenly deleted, but why this DNA is important is still not understood. Our data indicate that the deleted DNA encodes a suite of previously hidden genetic elements, and here we proposed using the latest high-throughput DNA and RNA sequencing and stem cell technologies to finally unravel this mystery.
The genetic material is packaged in the cell nucleus with histone proteins. Modifications of histones determine if a particular area of the genome is active or repressed. We are investigating the roles of a family of histone modifying proteins, the MYST proteins. Mutations in these proteins cause intellectual disability and cancer. The research program will provide knowledge that may become the basis for the development of drugs for the treatment of cancer and neurodegenerative disorders.
Chromatin Regulation Of Neural Stem Cell Multipotency
Funder
National Health and Medical Research Council
Funding Amount
$756,142.00
Summary
The genetic material is packaged in the cell nucleus with histone proteins. Chemical modifications of histones determine if a particular area of the genome is active or repressed. We are investigating a family of histone modifying proteins, the MYST proteins. Mutations in these proteins cause intellectual disability and cancer. In this project we examine the role of MYST2 in brain stem cells. Knowledge gained may become the basis for the development of drugs to treat neurodegenerative disease.
Effects Of The Histone Acetyltransferases MOZ And QKF On Chromatin Modifications
Funder
National Health and Medical Research Council
Funding Amount
$349,576.00
Summary
Cancer of the blood (leukaemia) can be caused by rearrangements of the genetic material (DNA) that cause fusions between ordinarily separate proteins. Monocytic leukaemia zinc finger (MOZ) fusion proteins cause aggressive leukaemia. We have shown that MOZ associates with DNA packaged with histone proteins into chromatin, changes histones and gene activity. We will examine how MOZ and the closely related QKF protein affect the chromatin to elucidate the function of MOZ and QKF.
Understanding The Control Of Brain Development And Endocrine Function Through Central Regulation Of Gene Transcription
Funder
National Health and Medical Research Council
Funding Amount
$624,846.00
Summary
Intellectual disability affects about 2% of the Australian population. The identification of genes underlying a number of intellectual disability disorders has brought about great clinical advances. However, our knowledge of how these genes influence processes of brain development and are important for intelligence is very limited. We propose to study the function of PHF6, the gene mutated in the Börjeson-Forssman-Lehmann intellectual disability syndrome, during brain development.
Elucidating The Tumour Suppressor Behaviour Of FUBP1 In Glioma
Funder
National Health and Medical Research Council
Funding Amount
$940,780.00
Summary
Treatment strategies for patients with invasive brain tumours are based on a WHO tumour grading system. This system does not account for differences within tumour types, although these can significantly affect treatment outcomes. This project aims to investigate new drug therapies for specific brain tumour types, and to identify new prognostic markers for these tumours. These studies will lead to more individualised treatments, which is critical to improving patient survival and quality of life.