Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific kno ....Genetic analysis of cohesin function and regulation in Drosophila. In yeast, a multiprotein complex, called cohesin, holds newly replicated chromatids together until the cell is ready to partition each chromatid into its daughter cells. We and others have shown that cohesins are regulated differently in animal cells. We propose to combine classical genetic analyses with two new and innovative techniques, time-lapse confocal microscopy of fluorescent proteins in living cells and gene-specific knockout techniques to study key cohesin regulators in Drosophila. These studies will provide us with novel insights into how multicellular organisms regulate the structure and stability of their chromosomes.Read moreRead less
The Cytochrome P450 Gene Super-family in Drosophila melanogaster; Gene Function and Insecticide Resistance. The cytochrome P450 (Cyp) gene super-family is represented by over 90 sequences in the genome of the vinegar fly, Drosophila melanogaster. To date, four Cyp genes are found to be involved in insecticide resistance. The function of the majority of Cyp genes is unknown. This project will investigate the function and regulation of D. melanogaster Cyp genes, linking the fly's genotype to its ....The Cytochrome P450 Gene Super-family in Drosophila melanogaster; Gene Function and Insecticide Resistance. The cytochrome P450 (Cyp) gene super-family is represented by over 90 sequences in the genome of the vinegar fly, Drosophila melanogaster. To date, four Cyp genes are found to be involved in insecticide resistance. The function of the majority of Cyp genes is unknown. This project will investigate the function and regulation of D. melanogaster Cyp genes, linking the fly's genotype to its phenotype. By studying the effects of Cyp genes on fly survival, Cyp gene expression and regulation, and expressing selected Cyp genes in a yeast expression system, we will enhance our understanding of Cyp gene function and evolution.Read moreRead less
Functional characterization of SSB2: a novel single-stranded DNA binding protein. Defects in the DNA damage response pathway underpin many human genetic disorders and diseases. A detailed understanding of this pathway has enormous implications for future medicine. The proposed research will lead to functional characterization of a new protein, identify new concepts in DNA damage repair pathways, train young researchers and place Australia among the leaders in this internationally significant and ....Functional characterization of SSB2: a novel single-stranded DNA binding protein. Defects in the DNA damage response pathway underpin many human genetic disorders and diseases. A detailed understanding of this pathway has enormous implications for future medicine. The proposed research will lead to functional characterization of a new protein, identify new concepts in DNA damage repair pathways, train young researchers and place Australia among the leaders in this internationally significant and highly competitive area of research. It will underpin the national research priority of Promoting and Maintaining Good Health and help Australia capitalise on a plethora of opportunities for future economic and health benefits.Read moreRead less
Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of hea ....Novel roles for importin alpha proteins in the nucleus. The project will provide fundamental new information about how changes in cell function are influenced by importin (IMP) alpha proteins, both through changes in gene transcription and through alterations to intracellular transport. These findings will inform areas of national priority that include Aging Well, Aging Productively with specific regard to cellular stress responses, and A Healthy Start to Life in the context of production of healthy, genetically intact sperm. This project draws together an international team to investigate a phenomenon with implications for new understanding of normal developmental processes and the response of cells/tissues to disease conditions.Read moreRead less
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.
Most eye diseases have a genetic contribution, whether rare disorders affecting children such as retinoblastoma or congenital cataracts through to common disorders of older people such as myopia, age-related macular degeneration or glaucoma. We will continue our successful research to find genes that cause these diseases and use this to improve patient care and prevent blindness. We will work out how families can use this genetic information to participate in trials to develop new treatments.
An Integrated Approach For The Efffective Adoptive Immunotherapy Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Killer T lymphocytes can penetrate tumors and their transfer into cancer patients has demonstrated some encouraging results, but this form of immunotherapy remain ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. The outcomes of this project will validate this novel approach for treatment of cancer patients.
The Role Of Transcriptional Co-activators And Co-repressors During Embryonic Development
Funder
National Health and Medical Research Council
Funding Amount
$82,421.00
Summary
Every creature starts out as a single fertilized egg. The genome directs the embryonic development of the egg by regulating the expression of genes each of which must be turned on or off at the correct time and place. This essential balance between the activation or repression of genes is controlled by groups of proteins, including ‘transcriptional co-activators’ and ‘repressors’. This project aims to better understand the role of these proteins during embryonic development.