Mechanism Of Action Of Sec1p-like Proteins In Membrane Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$234,936.00
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
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE100100074
Funder
Australian Research Council
Funding Amount
$520,000.00
Summary
Facilities for automated high-throughput slide scanning and stereology. The equipment requested will facilitate the work of the Australian Mouse Brain Mapping Consortium, a consortium of Australian research groups collaborating to provide the only mouse model brain mapping capability in the country. The consortium brings together laboratory, neuroimaging and computational expertise in a comprehensive framework for imaging the mouse brain. This will help researchers to study mouse models of genet ....Facilities for automated high-throughput slide scanning and stereology. The equipment requested will facilitate the work of the Australian Mouse Brain Mapping Consortium, a consortium of Australian research groups collaborating to provide the only mouse model brain mapping capability in the country. The consortium brings together laboratory, neuroimaging and computational expertise in a comprehensive framework for imaging the mouse brain. This will help researchers to study mouse models of genetic and acquired disorders across the life-span. Remote viewing and analysis capabilities will help overcome the 'tyranny of distance', increasing national access to the facility. Repositories of digitised images will increase the availability of valuable research material to other Australian and international researchers.Read moreRead less
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 implications of resistance training for the control of movement. Resistance training (or weight lifting) is an essential element of comprehensive rehabilitation programs in a wide range of clinical settings. However, because we know little about how the organization of the nervous system is affected by training with high loads, the consequences of resistance training for our ability to control functional movements are unclear. The ultimate goal of this research is to generate basic knowledge ....The implications of resistance training for the control of movement. Resistance training (or weight lifting) is an essential element of comprehensive rehabilitation programs in a wide range of clinical settings. However, because we know little about how the organization of the nervous system is affected by training with high loads, the consequences of resistance training for our ability to control functional movements are unclear. The ultimate goal of this research is to generate basic knowledge about the impact of resistance training on nervous system function. The research will lead to the design of injury prevention and rehabilitation programs that are maximally effective, and provide a genuine benefit to the community.Read moreRead less
Identifying genes that influence clinical course and susceptibility in multiple sclerosis. This project aims to identify the genetic basis of multiple sclerosis (MS), the most common neurologic disease in young Australian adults. MS urgently needs research to identify predisposition, aid early diagnosis and provide bona fide molecular targets for new therapies. This will benefit people with MS and those susceptible to it. Crucial new knowledge identified will benefit other major areas of MS rese ....Identifying genes that influence clinical course and susceptibility in multiple sclerosis. This project aims to identify the genetic basis of multiple sclerosis (MS), the most common neurologic disease in young Australian adults. MS urgently needs research to identify predisposition, aid early diagnosis and provide bona fide molecular targets for new therapies. This will benefit people with MS and those susceptible to it. Crucial new knowledge identified will benefit other major areas of MS research including epidemiology, immunology and neurobiology. Collaboration of 8 major Australian institutions is also important for this project and future studies. The team will have access to a new national MS GeneBank (platform) with samples from 2240 patients that should generate findings important to world-wide MS genetic knowledge.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0561030
Funder
Australian Research Council
Funding Amount
$441,100.00
Summary
Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiative ....Developmental Imaging Facility. This application seeks to establish a facility to undertake expression profiling in vertebrate tissues on a genomic scale and at the highest resolution. Undertaking large scale projects of this nature requires specialised robotics and dedicated infrastructure for microscopy and tissue preparation. This facility will be the first of its type in Australia will permit researchers to perform genomic scale in situ screens, many as part of large international initiatives in developmental and cellular biology. This large-scale, high-resolution expression profiling infrastructure is required to maintain international competitiveness and will dramatically improve our gene discovery, functional assessment and understanding of vertebrate development.Read moreRead less
Role of the complement system in the healthy and diseased central nervous system. The investigation into the role of the immune system in the central nervous system will increase our understanding of the causes behind the neurodegenerative process in aging individuals. This research will also indicate the potential for new types of anti-inflammatory drugs, to be used to slow the neurodegenerative process occurring naturally in the aging brain. These drugs could also be useful in treating drastic ....Role of the complement system in the healthy and diseased central nervous system. The investigation into the role of the immune system in the central nervous system will increase our understanding of the causes behind the neurodegenerative process in aging individuals. This research will also indicate the potential for new types of anti-inflammatory drugs, to be used to slow the neurodegenerative process occurring naturally in the aging brain. These drugs could also be useful in treating drastic neurodegenerative diseases such as motor neuron disease, Huntington's disease and Parkinson's disease. Of these, only Parkinson's disease currently has some effective treatments. Community and National benefits would be increased health, decreased stress and major economic savings.Read moreRead less
Special Research Initiatives - Grant ID: SR1101002
Funder
Australian Research Council
Funding Amount
$21,000,000.00
Summary
Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and ....Stem Cells Australia. Despite progress in stem cell research, scientists do not understand how stem cells “decide” what to become. Stem Cells Australia will draw upon strengths within Australia’s premier stem cell research universities and institutes. This collaboration between leading bioengineering, nanotechnology, stem cell and advanced molecular analysis experts, will fast-track efforts to deliver a fundamental understanding of the mechanisms of stem cell regulation and differentiation, and the ability to control and influence this process. Stem Cells Australia will deliver new methods for stem cell propagation and manipulation, new translational technologies for therapeutic applications, and will prepare Australia’s future stem cell scientific leaders.Read moreRead less
Linkage Infrastructure, Equipment And Facilities - Grant ID: LE0668246
Funder
Australian Research Council
Funding Amount
$400,000.00
Summary
Advanced Cell Labelling and Imaging Facility. Understanding the genetic regulation of cellular processes such as migration, differentiation and growth is an important frontier technology with significant biomedical potential. The Australian community is facing an increasing need to provide solutions for a variety of human diseases and disorders, including birth defects, nervous system injury and stroke, and ageing-related conditions. The proposed facility will allow researchers to test in vivo g ....Advanced Cell Labelling and Imaging Facility. Understanding the genetic regulation of cellular processes such as migration, differentiation and growth is an important frontier technology with significant biomedical potential. The Australian community is facing an increasing need to provide solutions for a variety of human diseases and disorders, including birth defects, nervous system injury and stroke, and ageing-related conditions. The proposed facility will allow researchers to test in vivo gene/pharmaceutical therapies as well as to better understand the genetic regulation of normal cellular processes. Read moreRead less