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.
Investigating Widespread Regulation Of Gene Expression Through Intron Retention
Funder
National Health and Medical Research Council
Funding Amount
$363,026.00
Summary
We recently discovered a hidden type of gene regulation that appears to be altered in diverse cancers including leukaemia, melanoma and colon cancer. We will explore this widely relevant mechanism using molecular and computational tools. We created the only computer program able to detect this type of regulation and will now share our discovery with cancer scientists through cloud computing technology.
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 .
A Novel Molecular Target Capable Of Abrogating Neuroblastoma Development
Funder
National Health and Medical Research Council
Funding Amount
$802,499.00
Summary
Although modern chemotherapy has significantly improved survival rates for many childhood cancers, the outlook remains dismal for children with advanced staged neuroblastoma. These patients frequently have alterations in the cancer-causing gene called MYCN. Using pre-clinical models of MYCN-driven neuroblastoma and genome sequencing we have discovered a gene that can completely block the action of MYCN and prevent neuroblastoma growth. This work will characterize the function of this novel gene.
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.
Computational Reconstruction And Validation Of A Gene Regulatory Network Controlling Differentiation Of B Cells To Antibody-secreting Plasma Cells
Funder
National Health and Medical Research Council
Funding Amount
$618,152.00
Summary
Regulation of B cell differentiation, which occurs when our body responds to antigen infection is tightly controlled by a gene regulatory network. This project will be the first study to reconstruct a regulatory network for this process by using genome-wide expression and transcription factor binding data. The research finding from this study will elucidate the molecular mechanisms regulating this process and will shed new light on how this network is altered in lymphoma and myeloma.