Transcriptional Complexity Of Cell Cycle Regulated Genes During Cell Division And Tumorigenesis
Funder
National Health and Medical Research Council
Funding Amount
$491,703.00
Summary
Massive scale transcriptome and genome annotation efforts have recently identified all genes encoding the cellular machinery of protein phosphorylation. The size of the molecular network of kinases and phosphatses has been found to be far more complex in mammals than previously reported, with many kinase and phosphatase loci generating, on average, more than 4 transcripts per gene. This grant is aimed at addressing the role of transcriptional complexity in the control of normal cell division and ....Massive scale transcriptome and genome annotation efforts have recently identified all genes encoding the cellular machinery of protein phosphorylation. The size of the molecular network of kinases and phosphatses has been found to be far more complex in mammals than previously reported, with many kinase and phosphatase loci generating, on average, more than 4 transcripts per gene. This grant is aimed at addressing the role of transcriptional complexity in the control of normal cell division and tumorigenesis using a systems wide approach. Rather than relying on the locus based study, this proposal seeks to take a systems biology approach, addressing the functional diversity of the expanded human phosphoregulator proteome, identifying all components of the network that are actively and dynamically expressed in the normal cell cycle and-or tumour progression, and then screening selected novel components for an ability regulate the cell cycle. Such studies will advance our understanding the involvements of the protein phosphorylation machinery in regulating cell division, highlight novel components potentially relevant tumorigenesis and potentially identify new chemotherapeutic targets.Read moreRead less
Harnessing The Power Of Genomics To Understand Disease
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
The last 10 years have seen a revolution in our ability to sequence DNA and related molecules. This technological advancement has the potential to transform our knowledge of the mechanisms of development and disease. In order to harness the power of this technology, advances in analysis strategies and methods are critical to extract the important insights into these massive data sets. My research will lead the way in several major areas of bioinformatics research.
Clinical Application Of Genomic Approaches For Cancer
Funder
National Health and Medical Research Council
Funding Amount
$707,370.00
Summary
Cancer is the cause of 1 in 8 deaths worldwide. Cancer occurs due to errors or mutations in the DNA of normal cells. I will identify the mutations in tumour cells, which will tell us: i) How the tumour started and grew ii) How to treat the tumour and kill the cancer The work involves a variety of cancer types including mesothelioma, melanoma, oesophageal and breast cancer. The overall aim is to apply some of the research findings or approaches into patient care to improve patient survival.
Using High-throughput Genomics To Reveal The Deleterious Genetic Changes That Underlie Paediatric Leukoencephalopathies
Funder
National Health and Medical Research Council
Funding Amount
$1,003,712.00
Summary
There has been an explosion of high-throughput DNA sequencing technologies in the past five years, which have the potential to completely revolutionise medicine and scientific research. Here we present a series of studies showing the successful application of this technology to children with genetic disorders of the central nervous system. This proposal seeks to expand this study to a large cohort of similarly affected paediatric patients.
Computational Approaches To Making Sense Of Cancer -omics Data
Funder
National Health and Medical Research Council
Funding Amount
$706,370.00
Summary
Evolution is a hallmark of cancer. It underlies tumorigenesis, metastasis, disease progression, the emergence of drug resistance, and patient death. My research will develop the essential bioinformatics methods and computational models to understand cancer evolution using -omics data, and apply these to discover the molecular mechanisms that cause complex genome rearrangements; investigate the evolution of advanced melanoma; and translate our tools and discoveries into the clinical setting.
Neuronal Genome Mosaicism: A Molecular Component Of Cognition?
Funder
National Health and Medical Research Council
Funding Amount
$687,975.00
Summary
The brain is a complex and dynamic organ tasked with interpreting and responding to the world around us. My recent work has shown that mobile genetic elements, or 'jumping genes', cause changes in the DNA of brain cells, potentially altering how they work. During the course of this fellowship, I will examine how and when during life these DNA changes occur, whether they play a role in memory formation, and whether they contribute to neurodevelopmental and mental health conditions.
Mechanistic And Functional Drivers Of Neochromosome Evolution
Funder
National Health and Medical Research Council
Funding Amount
$763,771.00
Summary
Neochromosomes are Frankenstein chromosomes--massive extra chromosomes that are stitched together from 100s of pieces of normal chromosomes. They are found in 3% of cancers, but are common in some types, such as liposarcoma. We have mapped their structure and found they form through punctuated chromosome shattering and gene amplification. We will investigate the precise molecular mechanisms that cause this and the recurrent transcriptional and epigenetic drivers lead to their formation.
Determining Shared Genetic Control Of RNA Transcription Across 45 Human Tissue Types
Funder
National Health and Medical Research Council
Funding Amount
$264,684.00
Summary
There is strong evidence that much of the genetic susceptibility to disease acts through altering way genes are turned into proteins via RNA transcripts. One important problem in using transcriptomic data to study diseases is that the genetic control of RNA transcription is known to vary between tissues. This study will use new methods and RNA data from 45 human tissues to show the degree of common genetic control for each RNA transcript between each pair of tissues.