The Unfolded Protein Stress Response In Inherited Skeletal Disease: Mechanism And Therapeutic Strategies
Funder
National Health and Medical Research Council
Funding Amount
$549,092.00
Summary
In genetic diseases, gene mutations commonly cause proteins to fold abnormally. This can cause cell stress resulting in cell death. Our studies will determine the role of cell stress in a clinically important group of skeletal diseases caused by collagen mutations. We will also test how we can use small chemicals to alleviate the damage done to the cells by the misfolded proteins, in the hope that this approach will provide new therapeutic strategies for these disorders.
Liver Cell Transplantation For The Treatment Of Liver Based Metabolic Diseases.
Funder
National Health and Medical Research Council
Funding Amount
$444,143.00
Summary
We propose to investigate the role of liver cell transplantation (LCT) for the therapy of inherited liver-based metabolic diseases using a methylmalonic aciduria (MMA) mouse model. LCT provides an exciting alternative to whole organ transplantation. Initially it was considered liver cells would be immunopriviledged. This has not proven to be the case. Immune modulation will be important. We will also examine immune modulation using antibodies to optimise longterm survival of allogeneic cells.
Multiple sclerosis (MS) is the most common neurological disease of young adults, with very high costs in loss of quality of life, reduced contribution of sufferers to the workplace, and in treatment. No cures exist and its cause is unknown. It is, however, known to be a largely genetic disease - but the genes associated with it have yet to be identified. An international consortium, known as GAMES (Genes Associated with Multiple Sclerosis) has now completed a screen of all human chromosomes usin ....Multiple sclerosis (MS) is the most common neurological disease of young adults, with very high costs in loss of quality of life, reduced contribution of sufferers to the workplace, and in treatment. No cures exist and its cause is unknown. It is, however, known to be a largely genetic disease - but the genes associated with it have yet to be identified. An international consortium, known as GAMES (Genes Associated with Multiple Sclerosis) has now completed a screen of all human chromosomes using 6000 markers to identify regions with genetic differences in multiple sclerosis patients. The Australian contribution to this study was funded by the NHMRC. This project is a continuation of the first, only moving on to fine-scale mapping of the regions identified in GAMES1, so that single genes, rather than genetic regions, are the focus for the study. It also aims to ensure Australian participation as an equal player in phase II of this major international collaboration. The Australian results will contribute to the overall study. If associations identified in single countries are found in other countries, this confirms the validity of the association. In addition, genes which are only slightly associated with disease in individual countries, may become more meaningful if they are found to be associated in the studies from other countries. In this way a sensitive and robust comparison of the genes which affect predisposition to MS will be identified and this information can be used to target molecular pathways for drug intervention.Read moreRead less
Develop New Approaches To Cancer Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$4,000,000.00
Summary
Apoptosis is the dominant focus of our planned studies, because its impairment is both a critical step towards malignancy and a barrier to effective treatment. Arguably, the laboratory heads within our division and our collaborators from the Structure Biology Division at WEHI constitute the world’s strongest group with this focus. Our accumulated experience in this field from its renaissance in 1988 and the many unique materials they have created superbly position us to answer the fundamental qu ....Apoptosis is the dominant focus of our planned studies, because its impairment is both a critical step towards malignancy and a barrier to effective treatment. Arguably, the laboratory heads within our division and our collaborators from the Structure Biology Division at WEHI constitute the world’s strongest group with this focus. Our accumulated experience in this field from its renaissance in 1988 and the many unique materials they have created superbly position us to answer the fundamental questions and translate them into new therapeutic approaches. Our team’s second focus, the links of stem cells to cancer, is also of great importance, because the rare stem cells in the tumour may dictate therapeutic outcome. This Fellowship aims to addresses fundamental issues with enormous potential for medicine. It builds on productive ongoing research by a team with diverse complementary expertise, a record of effective interaction, high momentum and a history of path-breaking discoveries. I plan to maintain and further develop our Division (the Molecular Genetics of Cancer Division at WEHI) as one of the strongest teams for cancer research and development of cancer therapies in the world. Our division contains several laboratories that are highly interactive and complimentary in their approaches and research interests. I plan to strengthen the already highly productive laboratories in our division and to develop some new ones (see below under ‘proposed team’). I plan to increase work of our division to also include studies on other solid tumours (e.g. colon cancer, lung cancer, prostate cancer). This Fellowships aims to greatly enhance cancer research and hopefully also clinical practice in Australia. This should enhance the reputation of Australia as a country with recognized excellence in medical research and clinical practice. I am also confident that our division will continue to educate outstanding PhD graduates and postdoctoral fellows who will in due course become independent researchers and develop into future leaders in medical research in Australia and-or overseas.Read moreRead less
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.