The 3’ UTR Codes That Control MRNA Translation In Development
Funder
National Health and Medical Research Council
Funding Amount
$609,281.00
Summary
We are the product of an exquisite programme that controls when and where genes are turned on and off, over time, from a single cell to adulthood. This project concerns codes that regulate this programme with a focus on early development, the germline and neuronal cells. Using the same technology that now allows individuals to sequence their own genome, we will study an aspect of this timing in model organisms having genetic lesions in specific pathways that relate also to human health and disea ....We are the product of an exquisite programme that controls when and where genes are turned on and off, over time, from a single cell to adulthood. This project concerns codes that regulate this programme with a focus on early development, the germline and neuronal cells. Using the same technology that now allows individuals to sequence their own genome, we will study an aspect of this timing in model organisms having genetic lesions in specific pathways that relate also to human health and disease.Read moreRead less
Antibiotic Tolerance And Small RNA Networks In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$521,559.00
Summary
Treatment of MRSA is restricted to last line antibiotics and treatment failure is associated with an intermediate tolerance to vancomycin. Regulatory molecules termed small RNA mediate responses to antibiotic challenge but their functions are poorly understood. This proposal will profile sRNA function to understand how they adapt S. aureus to antibiotic challenge. A molecular understanding of vancomycin-tolerance will inform development of diagnostics and treatment strategies.
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.
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.
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.
Role Of Sirtuins In The Regulation Of The Carcinogen Metabolising Arylamine N-acetyltransferases
Funder
National Health and Medical Research Council
Funding Amount
$327,324.00
Summary
This project will investigate critical biochemical pathways that regulate metabolic differences in normal and cancer cells. By understanding how these processes differ, novel approaches for detecting and managing cancer cell proliferation in humans may be achievable.
Mechanisms Of Antibiotic-induced Persistent Bacterial Infection
Funder
National Health and Medical Research Council
Funding Amount
$632,048.00
Summary
Golden staph still causes significant human infections and resistance to antibiotics is an ever growing problem with this bacteria. This project will determine how resistance to some antibiotics is also changing the bacteria to promote persistent, difficult to treat infections. The insights from this study will help understand evolution of this bacteria, and help design new strategies for management.
Identification Of Glaucoma Susceptibility Variants By Exome Sequencing In Extended Pedigrees Showing Prior Evidence Of Gene Segregation.
Funder
National Health and Medical Research Council
Funding Amount
$694,002.00
Summary
Primary open angle glaucoma is a chronic eye disease and one of the leading causes of visual impairment and blindness worldwide. This study will use cutting-edge genetic methods to look at the entire coding component of the human genome (exome) in 271 individuals from large glaucoma families. Our previous studies have shown that these families carry genetic variants that increase disease risk. In this investigation we aim to identify these genes, with the hope they may offer novel targets for tr ....Primary open angle glaucoma is a chronic eye disease and one of the leading causes of visual impairment and blindness worldwide. This study will use cutting-edge genetic methods to look at the entire coding component of the human genome (exome) in 271 individuals from large glaucoma families. Our previous studies have shown that these families carry genetic variants that increase disease risk. In this investigation we aim to identify these genes, with the hope they may offer novel targets for treatment or diagnosis.Read moreRead less
Epigenetic Signatures Of Abnormal Adult Neurogenesis In Rett Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$869,332.00
Summary
Rett syndrome (RTT) is a severe neurodevelopmental condition arising in early childhood. In Australia, RTT affects an estimated 1/8500 females. The vast majority of RTT patients carry a single mutation in the gene MeCP2. Recent advances in genetic engineering may allow MeCP2 mutations to be corrected in patients. This study will assess whether other molecular factors are involved in the RTT phenotype in patient neurons, and whether these factors are likely to be corrected by MeCP2 gene therapy.