Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specifi ....Drugging the undruggable: Development of novel technologies to selectively regulate the expression of targets driving cancer and other diseases. Transcription factors are “undruggable” targets playing a principal role driving cancer. This project will create novel therapeutic strategies to inhibit transcription factors and other elusive targets differentially expressed in diseased cells, without affecting normal tissue. It proposes to construct engineered proteins able to bind and modify specific key genes deregulated in cancer, to correct their expression and stably reprogram the phenotype of the tumour cell in a normal-like state. It outlines the engineering of novel synthetic agents to block specific protein-protein interactions in cancer cells and to induce potent tumour cell death. This work will generate novel and selective therapeutics to treat un-curable forms of tumours.Read moreRead less
Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A b ....Chromatin barriers in Plasmodium falciparum gene regulation. Malaria is a major world disease that kills around 2 million people annually. The genome of the causative agent has now been completely sequenced, but we still know very little of how and why some genes are activated while their neighbours are turned off. I will study the DNA barriers that separate such genes, and the proteins that interact with these regions to better understand how genetic regulation functions in these parasites. A better understanding of gene regulation in malaria parasites will help us to better combat the tricks utilised by this and other organisms to elude our immune systems.Read moreRead less
Novel Fragile X Syndrome Prevalence Estimates In 100,000 Australian Newborns, Prognostic And Health-economic Outcomes: A Retrospective Newborn Screening Study
Funder
National Health and Medical Research Council
Funding Amount
$769,866.00
Summary
Fragile X syndrome (FXS) is a common heritable cause of intellectual disability and co-morbid autism, caused by epigenetic silencing of the FMR1 gene. This will be the world’s largest FXS mutation prevalence study conducted in 100,000 newborns using a novel test targeting epigenetic changes, and will also explore the prognostic outcomes, costs and benefits associated with FXS newborn screening, providing conclusions regarding expanding the current newborn screening in Australia to include FXS.
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0775726
Funder
Australian Research Council
Funding Amount
$306,270.00
Summary
Australian Mirror of the UCSC Genome Database and Browser. Modern medical, biological, agricultural, and environmental research and industries are being transformed by access to genomic information that details the DNA sequence of various species, as well as of different strains and individuals within populations. This information is being generated at an exponentially increasing speed, and requires large computational resources. This facility will provide Australian researchers, R&D organizati ....Australian Mirror of the UCSC Genome Database and Browser. Modern medical, biological, agricultural, and environmental research and industries are being transformed by access to genomic information that details the DNA sequence of various species, as well as of different strains and individuals within populations. This information is being generated at an exponentially increasing speed, and requires large computational resources. This facility will provide Australian researchers, R&D organizations and industry with state-of-the-art genomic data storage and analysis capability, which will permit both public and proprietary access, and accelerate Australian research and development in genetic medicine, pharmaceuticals, animal breeding and biodiversity.Read moreRead less
Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease le ....Genomic and molecular characterisation of a novel Australian leishmania pathogen. Leishmaniasis is the second most serious protozoal disease after malaria. This project will help characterise the first Leishmania species identified in Australia providing molecular tools to monitor the pathogen and a detailed assessment of any potential risk to human health. Comparative analysis with more pathogenic species will help identify genes and mechanisms that determine the progression of human disease leading to the potential identification of new drug and vaccine targets. The methodologies and expertise developed will be used will be available to other research groups working on infectious diseases.Read moreRead less
Genetics of longevity and the delay of post-reproductive senescence. Ageing of the population in the coming decades will cause an increasing health care burden. Diseases of ageing such as Alzheimer's, heart disease, Parkinson's and a range of cancers, as well as impairments of ageing such as reduced mobility and cognitive ability are all caused or exacerbated by oxidative stress. With some exceptions, current medical practices focus on surgical repair or drug therapy to alleviate symptoms of ag ....Genetics of longevity and the delay of post-reproductive senescence. Ageing of the population in the coming decades will cause an increasing health care burden. Diseases of ageing such as Alzheimer's, heart disease, Parkinson's and a range of cancers, as well as impairments of ageing such as reduced mobility and cognitive ability are all caused or exacerbated by oxidative stress. With some exceptions, current medical practices focus on surgical repair or drug therapy to alleviate symptoms of ageing rather than addressing the physiological causes of ageing itself. Our project will provide understanding of natural systems that prevent age-related senescence due to oxidative stress. The goal is to identify novel and natural ways to maximise the fitness, well-being and self-sufficiency of people as they age.Read moreRead less
A new statistical framework to understand the biological basis of Ankylosing Spondylitis and other complex diseases. Ankylosing Spondylitis (AS) is a highly heritable and common inflammatory arthritis which causes stiffness and progressive fusion of the spine, decreased quality of life and reduced lifespan. There is no known cure for the condition. This project aims to identify genes and biological pathways involved in AS pathogenesis using a new statistical framework that will be applied to tho ....A new statistical framework to understand the biological basis of Ankylosing Spondylitis and other complex diseases. Ankylosing Spondylitis (AS) is a highly heritable and common inflammatory arthritis which causes stiffness and progressive fusion of the spine, decreased quality of life and reduced lifespan. There is no known cure for the condition. This project aims to identify genes and biological pathways involved in AS pathogenesis using a new statistical framework that will be applied to thousands of individuals with the disease. This project will improve understanding of the underlying mechanisms involved in AS pathophysiology, inform development of new drug treatments for the condition, and create a powerful new statistical approach that can be used to identify biological pathways which are important in the pathogenesis of other complex diseases.Read moreRead less
The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manip ....The biology, structure and function of bacterial virulence effectors. This project is closely aligned with the National Research Priority of Promoting and Maintaining Good Health and will establish a research framework to investigate novel virulence processes that allow bacterial pathogens to infect humans and cause disease. This fresh approach to the study of bacterial pathogenesis will sit outside classic genetic methods to investigate infection and immunity which rely heavily on genetic manipulation of the pathogen. Other than providing fundamental information on host-pathogen interactions, this work may lead to novel disease interventions by inhibition of bacterial virulence factor activity and/or enhancement of host inflammatory and immune responses.Read moreRead less
Developing methods for the analysis of massively parallel sequencing data in family studies. This project will develop analytical methods to use the latest, high-throughput method of generating sequencing data, i.e. the letters of the human genome alphabet. These tools will be used to identify the causal mutations in families with inherited disorders, leading to diagnostic tests for these families.
Developmental genetics of malaria parasites. This project aims to improve our understanding of malarial genetics. The sexual cycle of malaria parasites occurs in mosquitoes. After sex, parasite progeny multiply to form infective spores that are injected into people by mosquito bite. Development of male and female malaria parasite gametes and their fusion to produce a diploid zygote are well understood, but the subsequent process of meiosis, development of a cyst stage and the sporogenic process ....Developmental genetics of malaria parasites. This project aims to improve our understanding of malarial genetics. The sexual cycle of malaria parasites occurs in mosquitoes. After sex, parasite progeny multiply to form infective spores that are injected into people by mosquito bite. Development of male and female malaria parasite gametes and their fusion to produce a diploid zygote are well understood, but the subsequent process of meiosis, development of a cyst stage and the sporogenic process to create haploid progeny for new infections are poorly understood in molecular genetic terms. The project aims to dissect the unique genetics of these insect stages using a rodent malaria model to generate crosses of different malaria parasite lines to determine when recombination takes effect.Read moreRead less