Fungi are increasingly causing life-threatening infections. Little is known about the mechanisms underlying these infections. We will compare the genomes of high and low virulent fungal strains to gain insides into the basis of these differences by using C. gattii as model of a globally highly pathogenic fungus. The findings will be generalized by comparing the obtained results with the genomes of other important pathogenic fungi to develop a scientific basis for better treatment strategies.
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.
Evolutionary Response Of Dengue And Chikungunya Viruses To A Novel Biocontrol Method
Funder
National Health and Medical Research Council
Funding Amount
$421,681.00
Summary
Dengue and chikungunya are mosquito-transmitted viruses that present significant public health threats to Australia and the Asia-Pacific. This project will investigate whether dengue and chikungunya can adapt in response to a bacterium that limits replication of the viruses in the mosquito. The research will provide critical data to inform new mosquito control methods aimed at breaking the virus transmission cycle. More broadly, the research will allow us to understand how viruses adapt to strat ....Dengue and chikungunya are mosquito-transmitted viruses that present significant public health threats to Australia and the Asia-Pacific. This project will investigate whether dengue and chikungunya can adapt in response to a bacterium that limits replication of the viruses in the mosquito. The research will provide critical data to inform new mosquito control methods aimed at breaking the virus transmission cycle. More broadly, the research will allow us to understand how viruses adapt to strategies aimed at limiting their replication.Read moreRead less
DNA Barcoding Of Pathogenic Fungi As The Basis For The Development Of Novel Standardized Diagnostic Tools
Funder
National Health and Medical Research Council
Funding Amount
$560,398.00
Summary
Fungal infections are increasing and have major health impacts, with a high economic burden. Timely initiation of therapy is the key to improve patient outcomes. However, reliable identification tools for fungal pathogens are lacking. We will use comparative genome analysis to develop unique fungal signatures (DNA barcodes) and establish an online database to allow for rapid identification for diagnosis in the clinical setting and as a quarantine tool for border protection.
Comparative Analysis Of Human And Kangaroo Leishmania: Defining Human Pathogenicity Genes
Funder
National Health and Medical Research Council
Funding Amount
$539,334.00
Summary
Leishmaniasis is a global infectious disease affecting millions and killing thousands each year. This project will utilise the recent discovery in Australia of a related pathogen to identify novel parasite genes and pathways involved in virulence in humans. The latest techniques in comparative genomics and molecular biology will identify the genes that cause human disease . Appropriate genes will then be used to develope a novel vaccine using the Australian parasite.
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.
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.