Glycine Transporters regulate the concentration of glycine in the spinal cord and brain. It has been suggested that elevating glycine levels in these regions may be useful in treating pain and schizophrenia. This project will provide the basis for the development of new glycine transport inhibitors that may be used to treat these conditions.
The Treatment Of BOoking Gestational Diabetes Mellitus Study: The TOBOGM Study
Funder
National Health and Medical Research Council
Funding Amount
$2,197,280.00
Summary
Gestational diabetes mellitus (GDM) related pregnancy complications are reduced with treatment from 24-28 weeks pregnant. Many women are diagnosed/treated earlier without evidence of benefit and possible risk of harm. In TOBOGM women under 20 weeks pregnant with mildly raised blood glucose will be allocated by chance to either immediate treatment, or awaiting a repeat diabetes test at 24-28 weeks pregnant to decide treatment. Harmful and beneficial effects on mother and baby will be compared.
How Does Paternal Obesity Influence Offspring Glucose Tolerance?
Funder
National Health and Medical Research Council
Funding Amount
$503,398.00
Summary
Obesity and diabetes are closely related to these conditions in either parent, but how the father contributes is unclear. We have shown that normal females mated with obese fathers consuming high fat diet, produce offspring who develop glucose intolerance and impaired insulin secretion. This work will examine the mechanisms underlying this effect in the rat, testing a novel role for environmental factors in the father on disease in offspring that may be relevant to the growing obesity epidemic.
Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle ....Insulin resistance (the inability of ordinarily insulin-sensitive tissues such as muscle and adipose tissue to respond to insulin) contributes to a number of diseases including diabetes and obesity. A key metabolic step in these tissues is the uptake of glucose from the blood stream. This step is accelerated by insulin thus allowing efficient clearance of glucose from the bloodstream after a meal. Our laboratory has played a major role in showing that insulin regulates glucose uptake into muscle and adipose tissue by stimulating the movement of a glucose transport protein from inside the cell to the cell surface (see http:--www.imb.uq.edu.au-groups-james-glut4 for an animated description of this process). The purpose of this proposal is to dissect the molecular mechanisms by which this glucose transporter can be held inside the cell in the absence of insulin and then allowed to be released from this site moving to the surface in the presence of insulin. Our studies over the past 5 years have brought us much closer to understanding this process in detail. The identification of the molecules responsible for this regulatory step will not only aid our understanding of this process but it will also provide a valuable target for development of therapeutic agents that can be used to combat insulin resistance.Read moreRead less
The transcriptional co-repressor C-terminal Binding Protein (CtBP) in metabolic control. This project will provide insights into the genes that regulate the storage of fat. We will learn about basic biology but will also discover mechanisms that may be used to influence fat storage in human health. We will also consolidate Australia's expertise in the use of the genetic model organism, the worm C. elegans, and validate the findings in mammalian systems. Finally, the process of training young sci ....The transcriptional co-repressor C-terminal Binding Protein (CtBP) in metabolic control. This project will provide insights into the genes that regulate the storage of fat. We will learn about basic biology but will also discover mechanisms that may be used to influence fat storage in human health. We will also consolidate Australia's expertise in the use of the genetic model organism, the worm C. elegans, and validate the findings in mammalian systems. Finally, the process of training young scientists in these modern systems, will also equip future researchers to make additional contributions to Australia's research output.Read moreRead less
RNA splicing: factors and mechanisms. Most primary gene transcripts must have their noncoding intronic sequences spliced out before the mRNA can be translated. Moreover, alternative splicing enables cells to generate a far more proteins than there are genes in the nucleus. Based on our proven success with ZNF265 we will isolate novel RNA interactors and their partners, colocalize these in intranuclear compartments, and elucidate their effect on pre-mRNA splicing. This will provide timely spin-of ....RNA splicing: factors and mechanisms. Most primary gene transcripts must have their noncoding intronic sequences spliced out before the mRNA can be translated. Moreover, alternative splicing enables cells to generate a far more proteins than there are genes in the nucleus. Based on our proven success with ZNF265 we will isolate novel RNA interactors and their partners, colocalize these in intranuclear compartments, and elucidate their effect on pre-mRNA splicing. This will provide timely spin-offs to the Human genome Project and EST sequence information, where the finding of only approx. 30,000 genes in our genome highlights the important role of alternative splicing in generating the large proteome repertoire of cells. This will bring considerable benefits to science, society, and the biotech industry.Read moreRead less
A new mechanism of gene regulation. This project will advance our knowledge of how genes are switched on and off, by focusing on a very common class of gene regulatory proteins known as zinc finger proteins. The results of this study will improve our understanding of the fundamental molecular events that underpin gene regulation and how we might control it in fields such as biotechnology and gene therapy.
New mechanisms of DNA recognition by zinc-finger domains. The work described in this proposal carries long-term benefits to the health of Australians. Many debilitating diseases, including many varieties of cancer, arise as a result of a breakdown in the normal regulation of gene transcription. It is only once we have a thorough understanding of transcriptional regulation in normal organisms that we will be in a position to devise effective therapies to deal with the disorders that result from a ....New mechanisms of DNA recognition by zinc-finger domains. The work described in this proposal carries long-term benefits to the health of Australians. Many debilitating diseases, including many varieties of cancer, arise as a result of a breakdown in the normal regulation of gene transcription. It is only once we have a thorough understanding of transcriptional regulation in normal organisms that we will be in a position to devise effective therapies to deal with the disorders that result from aberrant gene expression. Our proposed research program also provides the opportunity to train younger scientists in state-of-the-art molecular and structural biology, thus representing a significant national benefit. Read moreRead less
Molecular mechanism of regulation of human renin mRNA. Genetic technologies and genomics research are an international priority likely to reap rich rewards intellectually and commercially. The shrinking of the once-touted gene number to a more modest level has been accompanied by a corresponding increase in the complexity in the protein products arising from each gene, and even more so the methods used by cells to control gene expression. By elucidating the latter for a key gene we will open up ....Molecular mechanism of regulation of human renin mRNA. Genetic technologies and genomics research are an international priority likely to reap rich rewards intellectually and commercially. The shrinking of the once-touted gene number to a more modest level has been accompanied by a corresponding increase in the complexity in the protein products arising from each gene, and even more so the methods used by cells to control gene expression. By elucidating the latter for a key gene we will open up new avenues for control of gene expression in various organisms. Devising novel means of chemically modulating stability of specific mRNA molecules will have beneficial implications for health, livestock production and agriculture.Read moreRead less
Mechanism Of Action Of Sec1p-like Proteins In Membrane Trafficking.
Funder
National Health and Medical Research Council
Funding Amount
$440,250.00
Summary
One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has ....One of the most important evolutionary changes that has occurred is the development of intracellular compartments. All eukaryotic cells possess numerous membrane-encased structures which provide the basis for intracellular specialisation. For example, in order to degrade unwanted components cells have developed degradative enzymes. It is vital for the cell that these enzymes are sequestered away from other cellular components to avoid destruction of valuable molecules. In addition, the cell has developed a complex assembly line of modifications that are added to proteins in a specific order as they travel to their final destination within the cell. This necessitates the accurate passage of molecules between compartments, a process known as vesicle transport. To orchestrate the complex network of vesicular transport steps between all of the various intracellular compartments it is necessary to employ complex machinery to guide and check that these steps occur with high fidelity. The goal of our research proposal is to define the function of one of the molecules involved in this control process, the so-called Sec1p proteins. The strength of our proposal lies in the diversity of our approach. We intend to explore the molecular advantages of a relatively simple eukaryotic organism, a yeast cell, and apply the findings obtained from this cell to a more complex but highly related vesicular transport process; that of the insulin-regulated movement of a glucose transporter in mammalian fat and muscle cells. While we intend to apply our findings to the treatment of patients with diabetes, it is our ultimate goal to be able to learn more about this fundamental cell biological process so that we can apply our knowledge to understanding many different disease states.Read moreRead less