Cellular determinants of retrotransposition. This project aims to understand the processes that control retrotransposition in a genome. Transposable elements make up more than 50% of human genomes. The accumulation of retrotransposons through millions of years of evolution has shaped the genomes of all eukaryotic organisms, including humans. Researchers have elucidated mechanisms the host uses to defend the genome against insertional mutagenesis by retrotransposons, but the cellular machinery an ....Cellular determinants of retrotransposition. This project aims to understand the processes that control retrotransposition in a genome. Transposable elements make up more than 50% of human genomes. The accumulation of retrotransposons through millions of years of evolution has shaped the genomes of all eukaryotic organisms, including humans. Researchers have elucidated mechanisms the host uses to defend the genome against insertional mutagenesis by retrotransposons, but the cellular machinery and genomic environments needed for retrotransposition are undefined. This project aims to use models to uncover the mechanisms that control retrotransposition. This is expected to reveal more about human origins.Read moreRead less
Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput ge ....Deciphering the regulatory principles of metazoan development. This proposal aims to elucidate how regulatory elements in the genome, known as enhancers, determine the identity and function of animal tissues. Currently, it is believed that enhancers cannot be traced across evolutionarily distant animals. The project uses novel concepts, computational and molecular approaches to identify deeply conserved enhancers. It further dissects the mechanism of function by proteomics and high-throughput genomics. The expected outcomes will overturn our current view on enhancer evolution and reposition our understanding of how enhancers are functionally encoded in the genome. The work is an important contribution to understanding cellular complexity and species evolution with wide-ranging impact in genetics.Read moreRead less
Evolution and function of fragmented animal mitochondrial genomes. This project will reveal why animal mitochondrial genomes are in pieces, and how fragmented mitochondrial genomes evolve and function. This project will discover whether or not fragmented mitochondrial genomes have functional advantages. Knowledge generated from this project will lead to new approaches to mitochondrial genetic diseases in humans.
Post-GWAS Functional Characterisation Of Breast Cancer Susceptibility Loci
Funder
National Health and Medical Research Council
Funding Amount
$764,632.00
Summary
Recent studies have identified regions within the human genome in which DNA sequence variations are associated with an increased risk of breast cancer. Several of these regions do not contain any known genes, suggesting that regulatory DNA sequences are responsible for the associated risk. The aim of this proposal is to identify and characterise these DNA sequences. Understanding how sequences variations in these regions contribute to breast cancer will provide novel avenues for therapy.
Engineering the defence-vigour balance for increased crop yield. This project aims to investigate a novel hypothesis to increase seed yield and vigour. Translating from a model system it will test whether the deliberate inactivation of a gene in tomato and banana, by RNA interference or genome editing, enhances performance. A dysfunctional gene in the viral defence pathway of the model plant species N. benthamiana boosted its seed yield and vigour. This project will investigate the enhancement, ....Engineering the defence-vigour balance for increased crop yield. This project aims to investigate a novel hypothesis to increase seed yield and vigour. Translating from a model system it will test whether the deliberate inactivation of a gene in tomato and banana, by RNA interference or genome editing, enhances performance. A dysfunctional gene in the viral defence pathway of the model plant species N. benthamiana boosted its seed yield and vigour. This project will investigate the enhancement, determine the consequences to the plant's defences, measure the balance between defence and vigour, and examine the risk of disease to such yield-enhanced crops. This is a radical departure from conventional approaches to crop improvement but if successful would provide an additional solution to the problem of future food security.Read moreRead less
Evolution of defensive and predatory venom in cone snails. This project aims to determine the molecular and cellular origins and mechanisms regulating venom production and release to establish how defensive venoms evolved in cone snails. Cone snails possess a remarkable ability to rapidly and reversibly switch between separate venoms in response to predatory or defensive stimuli, implying that these are separately evolved and regulated mechanisms. The investigators hypothesise that defensive ven ....Evolution of defensive and predatory venom in cone snails. This project aims to determine the molecular and cellular origins and mechanisms regulating venom production and release to establish how defensive venoms evolved in cone snails. Cone snails possess a remarkable ability to rapidly and reversibly switch between separate venoms in response to predatory or defensive stimuli, implying that these are separately evolved and regulated mechanisms. The investigators hypothesise that defensive venoms, originally evolved in the proximal venom duct to protect against threats such as cephalopod and fish predation, have been repurposed in the proximal duct to allow predators to become prey, facilitating the switch from worm to mollusc and fish hunting. The project aims to show the broad implications for the evolution of venoms in animals and discover the regulatory mechanisms driving venom peptide expression.Read moreRead less
Investigating Post-transcriptional Gene Regulation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
In this program, I will enhance our understanding of cancer gene regulation and provide novel avenues for the treatment of aggressive tumours. Using own data and that from collaborators, I will determine patterns of gene regulation in blood cancers and identify markers that predict disease outcome. I aim to understand how gene regulation can transform healthy cells into tumour cells and whether personalised treatment can kill tumour cells more effectively and prevent relapse and metastasis.
Macrophage Polarisation And Control Of Pulmonary Inflammation.
Funder
National Health and Medical Research Council
Funding Amount
$895,494.00
Summary
As key immune cells, macrophages are polarised to phenotypes that turn inflammation on or off. In cystic fibrosis, defective macrophage polarisation enhances inflammation and prevents lung repair. We are defining the molecules and cellular pathways that control this process and identifying targets for existing drugs that can be used to reprogram macrophages and restore lung repair to improve patient outcomes.
Immunomodulatory Vaccines In The Treatment Of Peanut Allergy
Funder
National Health and Medical Research Council
Funding Amount
$678,899.00
Summary
Peanut allergy is the most common cause of food-induced anaphylactic reactions in Australia and is a major burden to our healthcare system. Current clinical practice advice dietary avoidance to prevent fatal anaphylactic responses. We propose the use of an immunomodulatory vaccine to re-write the immune response to peanut antigens, from an allergic to a tolerant phenotype. This study will provide novel insights into rational approaches for manipulating immune memory to food allergens.