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Regulation Of Mitochondrial Gene Expression In Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,209.00
Summary
Mitochondria are microscopic powerplants that produce most of the energy in cells. Genes that make mitochondrial proteins must work properly to make the energy our bodies require for health. Defects in the expression of mitochondrial genes cause debilitating diseases for which there are no cures currently. A/Prof Filipovska will use new technologies to understand how these mutations cause disease and develop therapeutics for treatments of diseases caused by defects in mitochondrial genes.
I work on mitochondrial diseases, which are inherited disorders of metabolism that block conversion of food energy into chemical energy needed by our cells. We focus on understanding (i) the genetic basis of these disorders using approaches such as massively parallel sequencing, systems biology and experimental studies, and (ii) the detailed mechanisms of disease by studying cell lines from patients and animal models. We aim to develop better methods for diagnosis, treatment and prevention.
DNA damage response pathways play important roles in preventing the onset of cancer and regulating the clinical response to chemotherapeutics, and some of the relevant proteins have additional functions during normal development. This fellowship will study new a human protein with key roles in the formation of the lung, and its roles in preventing devastating consequences of normal oxidative damage to DNA, as well as additional fundamental mechanisms involved in preventing genome mutations.
New genomic technologies are revolutionizing biological research. RNA-seq is a recently developed high-throughput sequencing technology that provides scientists with much more detail how genes are regulated and expressed than any earlier technology. New tools developed by Professor Gordon Smyth are allowing researchers to use RNA-Seq technology to more accurately determine which genes are genuinely changing in the development of cancers and in response to cancer treatments.
Investigating Pathways To Alleviate The Burden Of Diabetes And Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$622,655.00
Summary
Diabetes affects more than 1.2 million Australians and up to 40% of these will develop complications including kidney disease. Excess blood sugar as the result of diabetes can accelerate a biochemical process called advanced glycation, which permanently alters proteins affecting their structure and function. My research will focus on identifying new therapies to target advanced glycation as well as dysfunction of cell power stations, mitochondria which is caused by advanced glycation.
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.
Defining Genomic Mechanisms Associated With Treatment Response, Drug Resistance And Early Blast Crisis In Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
Chronic myeloid leukaemia is a fatal disease if untreated. Most patients now survive with new drugs, but some still rapidly die. I aim to understand these differences by investigating the genetic makeup of patients at diagnosis. Some may have gene mutations that prevent drugs from working effectively. Mutations will be detected using technology that can search more than 30,000 genes at the same time. This work could lead to improved survival for more patients by finding new targets for therapy.
Personalised Genomics In Precision Medicine Of Psychotic Illness
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
This research program will utilise recent developments in genomic technology to make detailed high-resolution genetic maps of individuals with psychotic illness. Where conventional gene discovery approaches focus on differences at the population level this program will integrate the variation within individuals to determine the network architecture. This will be used to generate genetic profiles for personalised medicine and provide the basis for treatments that are tailored to individuals.
The overall goal of the program is to develop novel approaches to slow the progress or prevent neurodegeneration in patients with rare human genetic disorders. The second program is designed to develop novel therapeutics from snake venom proteins. These include proteins with anti-bleeding activity and those with application in wound healing. The third program involves the development of novel biomarkers for the early detection and prognosis in prostate cancer.