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Nocturnin: A Post-transcriptional Regulator Of Circadian Fat Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$574,696.00
Summary
Our metabolism is aligned with the 24-hour rotation of the earth in what is termed the circadian clock. Being misaligned to this clock explains jetlag and the poor health associated with shift-workers. For example, whether fat is utilised or stored depends on the time of day. This study aims to investigate the post-transcriptional mechanisms that underpin the rhythmic changes that occur throughout our bodies to ensure that our metabolism is matched to our environment.
The 3’ UTR Codes That Control MRNA Translation In Development
Funder
National Health and Medical Research Council
Funding Amount
$609,281.00
Summary
We are the product of an exquisite programme that controls when and where genes are turned on and off, over time, from a single cell to adulthood. This project concerns codes that regulate this programme with a focus on early development, the germline and neuronal cells. Using the same technology that now allows individuals to sequence their own genome, we will study an aspect of this timing in model organisms having genetic lesions in specific pathways that relate also to human health and disea ....We are the product of an exquisite programme that controls when and where genes are turned on and off, over time, from a single cell to adulthood. This project concerns codes that regulate this programme with a focus on early development, the germline and neuronal cells. Using the same technology that now allows individuals to sequence their own genome, we will study an aspect of this timing in model organisms having genetic lesions in specific pathways that relate also to human health and disease.Read moreRead less
Role Of Sirtuins In The Regulation Of The Carcinogen Metabolising Arylamine N-acetyltransferases
Funder
National Health and Medical Research Council
Funding Amount
$327,324.00
Summary
This project will investigate critical biochemical pathways that regulate metabolic differences in normal and cancer cells. By understanding how these processes differ, novel approaches for detecting and managing cancer cell proliferation in humans may be achievable.
Antibiotic Tolerance And Small RNA Networks In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$521,559.00
Summary
Treatment of MRSA is restricted to last line antibiotics and treatment failure is associated with an intermediate tolerance to vancomycin. Regulatory molecules termed small RNA mediate responses to antibiotic challenge but their functions are poorly understood. This proposal will profile sRNA function to understand how they adapt S. aureus to antibiotic challenge. A molecular understanding of vancomycin-tolerance will inform development of diagnostics and treatment strategies.
Alternative Splicing- A Regulatory Mechanism Determining Self-renewal And Pluripotency Of ES And IPS Cells
Funder
National Health and Medical Research Council
Funding Amount
$664,650.00
Summary
Stem cells hold great promise in cell replacement therapies and may provide models to study human diseases and to screen new pharmaceuticals. For successful future therapeutic applications, a deeper understanding of the molecular mechanisms governing the behavior of stem cells is crucial. In this proposal we will investigate the role of alternative splicing in the control of the fundamental properties of stem cells, and identify target RNAs and gene expression networks regulated by splicing fact ....Stem cells hold great promise in cell replacement therapies and may provide models to study human diseases and to screen new pharmaceuticals. For successful future therapeutic applications, a deeper understanding of the molecular mechanisms governing the behavior of stem cells is crucial. In this proposal we will investigate the role of alternative splicing in the control of the fundamental properties of stem cells, and identify target RNAs and gene expression networks regulated by splicing factors.Read moreRead less
Understanding How RUVBL1 And RUVBL2 Organise Chromosomes And Their Links To Disease
Funder
National Health and Medical Research Council
Funding Amount
$605,005.00
Summary
Our proposal will provide a deep mechanistic framework to inform both clinicians in diagnosis and management of RUVBL related diseases and also therapeutically, as industry looks to use these proteins as drug targets. The great excitement of RUVBL in translation has outpaced the gathering of vital knowledge underpinning the function; knowledge this proposal will provide for the first time.
The Role Of Novel And Essential Bromodomain Proteins In Coordinating Malaria Parasite Gene Regulation And Their Potential As Anti-malarial Targets
Funder
National Health and Medical Research Council
Funding Amount
$689,034.00
Summary
Malaria kills over 400,000 people a year and new therapies are needed. Malaria parasites activate groups of genes by novel mechanisms that could be targeted by drugs. We will characterise a novel group of proteins to identify those that activate genes essential for parasite survival. We will also search for molecules that inhibit the proteins and kill malaria parasites. Thus we will discover how parasites control their genes and identify drug targets and inhibitors for drug development.
Supporting A Friend: The Role Of The Molecular Scaffold CoREST Family In Chromatin Regulation And Neuroprotection
Funder
National Health and Medical Research Council
Funding Amount
$354,802.00
Summary
In diseases such as Alzheimer’s disease, Parkinson’s disease and motor neuron disease, neurons degenerate and die. One contributing factor to neuronal death is inflammation. The aim of this study is to identify mechanisms that protect neurons from death. This project focuses on the role of a family of proteins (CoREST1-3) that function to reverse gene expression changes in inflammation that lead to neurodegeneration.
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.
Overcoming The Differentiation Block In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$811,669.00
Summary
Acute myeloid leukaemia (AML) is an aggressive leukaemia with poor overall survival. About 50% of AML cases have genetic mutations that disable PU.1, which in turn alters the expression of many other genes that cause leukaemia. We have developed new AML models allowing reversible inhibition of PU.1, and have shown that re-engaging PU.1 function causes AML regression. This project aims to understand PU.1 functions in AML and identify rational drug targets for treatment-resistant disease.