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.
Identifying Key Players In The Spread Of Antimicrobial Resistance
Funder
National Health and Medical Research Council
Funding Amount
$817,448.00
Summary
Antibiotic drugs are essential to treat bacterial infections. However some bacteria have genes that allow them to resist certain drugs, which can be transferred among bacteria to create 'superbugs' that can resist nearly all the drugs we have. This project investigates the transfer of drug resistance genes between Gram negative bacteria (common agents of food poisoning, hospital infection, UTI, etc) and aims to identify the bacteria and genes most important in the spread of superbugs in Australi ....Antibiotic drugs are essential to treat bacterial infections. However some bacteria have genes that allow them to resist certain drugs, which can be transferred among bacteria to create 'superbugs' that can resist nearly all the drugs we have. This project investigates the transfer of drug resistance genes between Gram negative bacteria (common agents of food poisoning, hospital infection, UTI, etc) and aims to identify the bacteria and genes most important in the spread of superbugs in Australia.Read moreRead less
Clonal Evolution In Myelodysplasia And Acute Myeloid Leukaemia Following Azacitidine
Funder
National Health and Medical Research Council
Funding Amount
$853,005.00
Summary
The myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) represent a spectrum of clinically heterogeneous malignancies that remain incurable in the vast majority of patients. Whilst the DNA mutations underpinning the initiation/maintenance of these malignancies are largely known we have little insight into how these mutations alter response to therapy. Using a range of sophisticated cutting edge technologies we will study how these DNA mutations evolve over the course of treatment.
A Functional Assay To Classify Genetic Variants In Lynch Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$368,195.00
Summary
At least one person in every 1000 is affected by Lynch syndrome, in which faulty DNA repair machinery causes high rates of cancer. People with Lynch syndrome can have their risk of cancer cut substantially with regular screening. However, we often struggle to understand whether people with 'non-standard' DNA sequences in particular genes actually have Lynch syndrome. This project develops a simple test that will tell clinicians whether a given sequence change relates to Lynch syndrome or not.
Fighting Epidermal Skin Cancers By Targeting Epidermal Clones That Accumulate Mutations
Funder
National Health and Medical Research Council
Funding Amount
$1,149,373.00
Summary
Common skin cancers such as basal and squamous cell carcinomas (BCC and SCC) are by far the most frequent cancer worldwide and require over a million interventions per year in Australia. This project will identify the skin cells that are most susceptible to give rise to cancer if excessively exposed to the sun and explores ways to prevent cancer formation. This will inform on new strategies to prevent new skin cancer development.
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
Statistical Methods For Identifying Structural Variation In Tumour Genomes Using Next Generation Sequencing
Funder
National Health and Medical Research Council
Funding Amount
$243,458.00
Summary
New DNA sequencing technology can sequence a tumour genome affordably in 2 weeks. This re-sequencing data can be used to find small mutations and large-scale chromosomal rearrangements that together are the drivers of cancer. These may one day be used to guide cancer therapy. This project will develop new algorithms for finding mutations and apply these to discover the genetic basis of drug resistance in a model lymphoma system.
Integrating Immunity And Genetics In Follicular Lymphoma To Establish A Prognostic Score Fit For The Modern Era
Funder
National Health and Medical Research Council
Funding Amount
$1,377,174.00
Summary
Follicular lymphoma (FL) is divided into early and advanced stages. Early stage FL is frequently cured, but there is no way to identify who will be cured and who won't. By contrast advanced stage FL is incurable. Our unique access to well-annotated clinical trial and population based cohorts allows us to perform a detailed biological comparison of early and advanced FL, to gain a deeper understanding of the impediments to eradicating the disease, and to predict outcome to conventional therapy.
Development Of Therapeutically Useful Human Artificial Chromosomes For Gene Delivery And Optimal Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$496,986.00
Summary
Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in ....Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in terms of infection, immune response, and germline modification. We have developed the first stage of a new technology for gene delivery that does not require the use of viruses. This technology is based on the generation of human artificial chromosomes, which are smaller versions of the naturally occurring chromosomes that carry all the genes inside our cells. Safety in these artificial chromosomes comes from the use of entirely human materials for their engineering. These artificial chromosomes also have other advantages over the viral approaches, including allowing large genes to be carried, and providing a permanent cure in a single treatment. We have already successfully constructed, published, and patented a number of first-generation human artificial chromosomes. The current project aims to complete the next proof-of-concept milestone towards the further development of this technology. Specifically, we propose to demonstrate the ability of the artificial chromosomes to carry genes and provide sustainable expression of these genes in cells and in animal models. Success in this study will allow the technology to proceed rapidly into commercialisation and clinical trial as a new improved tool for gene delivery and gene therapy.Read moreRead less
Discovering And Targeting Genes Regulating Skeletal Muscle Function, Metabolism, And Adaptations To Exercise Interventions
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Muscle wasting and decreased in mitochondrial function due to ageing or lack of physical activity are associated with reduced quality of life. The overarching aim is to develop a unique research program focusing on targeting specific genes, and to discover novel genes regulating muscle wasting and mitochondrial (dis)function. I anticipate this approach to assist in the development of targeted and personalised prevention and therapy for diseases associated with muscle (dis)function.