The Structure And Organization Of The Mitochondrial Genome In Health And Mitochondrial Disease
Funder
National Health and Medical Research Council
Funding Amount
$553,646.00
Summary
Mitochondrial DNA (mtDNA) mutations and mitochondrial dysfunction have been associated with a wide range of multi-system human diseases, although much remains to be learnt about molecular mechanisms in the pathogenesis of these diseases. Our goal is to understand how the expression of the mitochondrial DNA is regulated by mtDNA-binding proteins that will allow us to provide important insights into the molecular mechanisms of mitochondrial diseases.
We are seeking to understand how the protein ADAR1 functions. When it is mutated, ADAR1 can cause a range of diseases, most notably in a subset of Aicardi-Goutieres syndrome (AGS) patients, an autoimmune disorder affecting the brain, immune system, and skin. We have identified how we think that changes in ADAR1 activity may ultimately cause disease. This application will allow us to test this mechanism experimentally.
L1 Retrotransposition In Human Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$414,085.00
Summary
Retrotransposons are mobile genes that copy-and-paste themselves in the human genome. Previously thought to represent ñjunk DNAî, retrotransposons are increasingly being found to play important roles in biology. This fellowship will allow Dr Faulkner to research the consequences of retrotransposons being active in the body during development, and in adulthood, as a potential cause of cancer.
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.
Understanding The Role Of Chromosome Condensation Proteins And Their Link To Disease
Funder
National Health and Medical Research Council
Funding Amount
$601,224.00
Summary
Cells divide through a complex cascade of signals from our genetic material (DNA) which need to be finely tuned for events to occur properly. Errors in control cause faulty cell division and lead to diseases such as cancer. We have identified a master controller of these events termed the condensin complex and aim to understand how it orchestrates these functions by creating a map of its DNA location and understanding which regions in the genetic material it controls and how.
Molecular Insights Into Long Noncoding RNA-protein Complexes: Important Gene Regulators In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$388,927.00
Summary
Cancer cells turn good genes off and bad ones on: but how do they do this? Recent breakthroughs suggest that noncoding RNA, produced from so-called ‘junk’ DNA, is important. One such noncoding RNA forms paraspeckles, a novel component of the cell machinery. Here, we will pick apart the way paraspeckles are organised and function, to develop them as a prototype for designing anti-cancer treatments against noncoding RNAs.
Nuclear Retention-and-release Of RNA: A Naturally-occurring Mechanism For Controlling Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$428,753.00
Summary
The deliberate retention of messenger RNA in the nucleus is a newly-discovered biological mechanism used by cells to control which genes are made into proteins, and when. This is a fundamental process in health and disease. The project will employ cutting edge molecular and cellular techniques to discover the principles underpinning nuclear retention. These insights will allow the development of new methods to spatially and temporally control gene expression in diverse gene therapy applications.