Control Of Genome Regulation And Its Role In Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Changes in DNA can lead to differences in susceptibility to developing many diseases. The most common mechanism by which this occurs is through changing when and in which tissues disease-relevant genes get translated into proteins. My research focuses on understanding how DNA changes result in altered gene expression and how this can affect disease susceptibility. This work requires the use of high performance computing and statistical analysis of large genome-scale datasets.
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.
Novel Skeletal Muscle Enriched Genes In Muscle Biology And Disease
Funder
National Health and Medical Research Council
Funding Amount
$900,467.00
Summary
Each year hundreds of Australians are born with genetic muscle diseases, however, current methods fail to identify the causative disease gene in ~50% of patients. Here we will use expression patterns in skeletal muscle to prioritize novel candidate disease causing genes. We will functionally test the role of genes expressed in skeletal muscle cells using novel experimental assays. Uniquely, we will for the first time incorporate a novel class of gene (long non-coding RNAs) into our study.
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.
Investigating The Molecular Signature Of ASD Through Integrative Genomics
Funder
National Health and Medical Research Council
Funding Amount
$621,128.00
Summary
Autism is the most severe end of a spectrum of neurodevelopmental conditions, autism spectrum disorders (ASD). We have identified a signature of genes dysregulated in the brain of autistic individuals. The proposed project will investigate how the molecular signature of autism is regulated in the brain, and whether genetic variants in regulatory DNA contribute to the genetic architecture of ASD.
Application Of Next Generation Sequencing To Address Clinical Problems In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$463,652.00
Summary
Cancer is the cause of 1 in 8 deaths worldwide. Cancer occurs due to errors or mutations in the DNA of normal cells. The mutations may cause the cells to grow incorrectly and become cancer. I will identify the mutations or errors in tumour cells. This will tell us: i) How the tumour started and continued to grow ii) How to treat the tumour cells to kill the cancer The work will involve a variety of cancer types including mesothelioma, melanoma, oesophageal, pancreatic and breast cancer.
LINEs Of Mutagenesis, Selection And Evolution In Ovarian Cancer And Chemoresistance
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
L1 elements are powerful mutagens encoded within the human genome that becomes active in epithelial tumours. I will define the broad effects of L1 elements on the evolution of chemoresistance, focusing on ovarian cancer as a model system. Ovarian cancer is characterised by a poor 5 year survival rate of ~40% with most tumours developing resistance. Understanding the impacts of L1 on this evolution will inform the development and selection of more effective treatments for ovarian cancer.
An Indigenous Australian Reference Genome: Indigenous Inclusion In The Benefits Of Genomic Medicine
Funder
National Health and Medical Research Council
Funding Amount
$1,428,508.00
Summary
This project will establish an Indigenous Australian reference genome (the NCIGrg) within the National Centre for Indigenous Genomics (NCIG) using advanced genome sequencing technologies and data analytics and evaluate its research and clinical utility. The NCIGrg will be cornerstone of future genomic research and its clinical application in Indigenous communities. It will underpin NCIG’s commitment to ensuring that Indigenous Australians are included in the benefits of genomic medicine.
Characterising The Molecular Basis Of Cystic Kidney Diseases Using Kidney Organoids Created By Directed Differentiation Of Patient-derived, Induced Pluripotent Stem Cells.
Funder
National Health and Medical Research Council
Funding Amount
$122,714.00
Summary
Inherited genetic mutations cause almost half of chronic kidney diseases in children. In most cases we do not know what the mutation is or how it causes kidney disease. In this study we will turn skin cells from children with kidney disease into stem cells and then use these to make a mini-kidney in a dish. This will act as a model of kidney disease allowing us to understand what the problem is at the level of changes within the cells. This may result in new ways of treating kidney disease.
Discovery And Characterisation Of Long Noncoding RNAs In Human Neurological Disorders
Funder
National Health and Medical Research Council
Funding Amount
$349,647.00
Summary
Numerous regions in our DNA influence how likely we are to develop various diseases, including brain disorders such as Autism and Schizophrenia. However, in many of these regions no genes have been found and they appear “empty”, making it difficult to uncover what’s triggering the disease. This project will use a powerful new technology to discover new genes hidden within these supposedly “empty” regions that are important in brain disorders and investigate how they contribute to disease.