Matching Between Codon Usage And TRNA Abundance Determines The Expression Of Targeting Genes In Mammalian Cells
Funder
National Health and Medical Research Council
Funding Amount
$358,500.00
Summary
This proposal is about optimal production of protein drugs (biopharmaceuticals), using genetic engineering in the laboratory and gene therapy in patients. It will explore the science behind a novel observation that the optimal way to use the genetic code to encode proteins for production varies from cell to cell in the lab, and from tissue to tissue in patients. If successful, a simple test can be used to decide the optimal genetic code for a specific application.
Novel Probiotics And Naturally-sourced Extracts As Treatment Strategies For Chemotherapy-induced
Funder
National Health and Medical Research Council
Funding Amount
$322,183.00
Summary
Intestinal mucositis is a serious disorder associated with chemotherapy treatment in cancer patients. Recently, a new strain of probiotic bacteria has been described with the potential to decrease the severity of intestinal mucositis. However, it is not known whether the live probiotic is necessary for this effect. We will compare the live probiotic, dead probiotic and factors sourced from this probiotic for the potential to decrease the severity of intestinal mucositis. Similarly, there have be ....Intestinal mucositis is a serious disorder associated with chemotherapy treatment in cancer patients. Recently, a new strain of probiotic bacteria has been described with the potential to decrease the severity of intestinal mucositis. However, it is not known whether the live probiotic is necessary for this effect. We will compare the live probiotic, dead probiotic and factors sourced from this probiotic for the potential to decrease the severity of intestinal mucositis. Similarly, there have been anecdotal claims of medicinal application for so-called ‘bioactive’ extracts and formulations derived from a range of mammalian, marine and plant sources. Specifically, Lyprinol (an extract derived from the New Zealand Green-Lipped Mussel), Emu Oil (derived from Emu meat) and the herbal extract Iberogast, have been reported to possess antiinflammatory properties. Indeed, these agents are used widely for the adjunctive relief of symptoms associated with arthritis and joint pain. However, these agents have yet to be tested for their potential to treat or prevent intestinal mucositis. For the first time, utilizing proven, controlled animal model systems, the current submission will explore the therapeutic potential of these agents, alone and in combination with indicated probiotics, for their capacity to treat or prevent mucositis. Should efficacy be demonstrated, a potential mechanism of action will be sought by investigating effects on intestinal stem cells.Read moreRead less
Role Of The Anaphase-Promoting Complex Activator Cdh1 In Oocyte Maturation And Meiotic Aneuploidy
Funder
National Health and Medical Research Council
Funding Amount
$526,878.00
Summary
Eggs containing an incorrect number of chromosomes are described as aneuploid. This project sets out to examine the molecular causes of aneuploidy and why it increases with female age. We focus on the protective role of the protein Cdh1 in this process. The outcome would be to better understand the origins of aneuploidy so as to find methods of decreasing it as women age. This is highly significant given aneuploidy is the leading cause of early embryo loss and produces Down Syndrome babies.
Head Development: Genetic Determinants And Tissue Potency
Funder
National Health and Medical Research Council
Funding Amount
$947,116.00
Summary
Congenital malformations involving major defects of brain (anencephalus and related anomalies) and facial structures (ear, face and neck) are encountered in 3.4 and 1.4 per 10000 births respectively (Congenital Malformations Australia 1981-1996, National Perinatal Statistics Unit) and they constitute a substantial clinical burden. It is believed that these major structural defects usually result from abnormal development in the first trimester, which coincides with the time frame for the formati ....Congenital malformations involving major defects of brain (anencephalus and related anomalies) and facial structures (ear, face and neck) are encountered in 3.4 and 1.4 per 10000 births respectively (Congenital Malformations Australia 1981-1996, National Perinatal Statistics Unit) and they constitute a substantial clinical burden. It is believed that these major structural defects usually result from abnormal development in the first trimester, which coincides with the time frame for the formation of the basic components of the embryonic head in the mouse. Knowledge of the formation of the head in the mouse model is therefore relevant to the understanding of related developmental processes in early human development. This project which involves the application of sophisticated embryological and molecular analyses on mouse embryos generated by transgenesis and genetic manipulation provides a detailed studies of craniofacial morphogenesis in a mammalian model for early human development. The micro-manipulation procedures, embryo culture, fluorescence microscopy and the in situ hybridization are routinely performed in our laboratory, and most of the mouse lines are well established in my laboratory. Experiments proposed for this project that focus on the embryological and molecular analysis of normal and mutant embryos should discover new information on the cellular and molecular mechanisms that regulate head development. The knowledge will also offer insight into the pathogenesis of similar craniofacial malformations in other mutant embryos.Read moreRead less