Remodelling Of Bacterial Outer Membranes: Implications For Vaccine Development.
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
We have identified proteins located in bacteria that are responsible for growth and the transport of essential nutrients. We will use a combination of bacterial genetics, protein biochemistry and immunological techniques to fully characterize these proteins. This strategic knowledge has direct implications for vaccine development and National security, since similar species of bacteria were amongst the first biological weapons.
Establishing the role of heterotrimeric G-proteins in plant defence. Agriculture is an important economic activity in Australia that resulting in considerable export revenues. Agricultural losses caused by plant pathogens account for millions of dollars every year and have profound economic and social implications.
The proposed research will explore new approaches to increase plant resistance to pathogens using a previously unkown component of this network: G-proteins and could ultimately reduc ....Establishing the role of heterotrimeric G-proteins in plant defence. Agriculture is an important economic activity in Australia that resulting in considerable export revenues. Agricultural losses caused by plant pathogens account for millions of dollars every year and have profound economic and social implications.
The proposed research will explore new approaches to increase plant resistance to pathogens using a previously unkown component of this network: G-proteins and could ultimately reduce dependency on toxic chemical products.Read moreRead less
Physiological Significance Of Cellular Translocation Of The Intestine-specific Homeodomain Protein Cdx2
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Ulcerative colitis and Crohn's disease are debilitating inflammatory diseases of the bowel. Conservative estimates (Australian Crohn's and Colitis Association) suggest that at least 23,000 Australians are affected (>1 in 1000). Ten years after onset, there is an estimated risk of 0.5-1.0% per year of pancolitis patients developing full-blown bowel cancer. Current therapies for colon cancer are not very effective and the median survival for patients with metastatic disease is poor at 7-12 mont ....Ulcerative colitis and Crohn's disease are debilitating inflammatory diseases of the bowel. Conservative estimates (Australian Crohn's and Colitis Association) suggest that at least 23,000 Australians are affected (>1 in 1000). Ten years after onset, there is an estimated risk of 0.5-1.0% per year of pancolitis patients developing full-blown bowel cancer. Current therapies for colon cancer are not very effective and the median survival for patients with metastatic disease is poor at 7-12 months. It is therefore important to increase our understanding of the biology underlying these inflammatory conditions so that more effective treatments may be developed and fewer patients proceed to the cancerous stage. We have recently demonstrated a novel interaction between two proteins that may be relevant to intestinal inflammation. Surprisingly, the two proteins would not normally be expected to coincide with each other because of their different localisations within cells and tissues. The first protein, Cdx2, is only synthesised by intestinal lining cells and normally resides in the nucleus where it activates genes that play a role in the highly specialised absorptive functions of the intestine. The other protein, acrogranin-granulin, is more widely distributed in the body and is generally transported out of cells shortly after it has been made. It has been shown to interact with receptors on epithelial cells and blood cells and promotes their growth. In this proposal we will be investigating whether the complex formed between Cdx2 and granulin is important for normal physiology. Moreover since elevated levels of granulin are associated with inflammation, we aim to determine whether the Cdx2-granulin complex is formed during the active phase of ulcerative colitis and Crohn's disease. Specifically, we will test the hypothesis that the Cdx2-granulin complex plays an important role in repairing the damage caused to the lining of the intestine during inflammation.Read moreRead less
Regulation Of Nuclear Import Of Viral Oncoproteins And Transcription Factors By Protein-protein Interactions
Funder
National Health and Medical Research Council
Funding Amount
$650,383.00
Summary
The present application examines the controls that exerted over proteins that localize in the nucleus of eukaryotic cells. This relates relates integrally to cellular processes such as growth, development and oncogenesis. This research area is not represented elsewhere in Australia, and the particular experimental strategies to approach the problem, revolving around the use of special quantitative microscopic techniques are novel internationally. One part of the application seeks to examine tran ....The present application examines the controls that exerted over proteins that localize in the nucleus of eukaryotic cells. This relates relates integrally to cellular processes such as growth, development and oncogenesis. This research area is not represented elsewhere in Australia, and the particular experimental strategies to approach the problem, revolving around the use of special quantitative microscopic techniques are novel internationally. One part of the application seeks to examine transport within the cell of complexes of interacting proteins, rather than single proteins, under as close as possible to physiologically relevant conditions. This will be truly unique, and of great importance to our comprehension of eukaryotic cell function. This application examines particular types of negative control over protein nuclear localization. Since many proteins show such regulation, and in particular important proteins controlling cell growth and division, the results are fundamentally important to our understanding of how cells function in general. Further, this understanding may be applied in disease situations, such as viral-mediated oncogenesis. In the work we propose to do, viral proteins with functions relating to cancer will be examined in detail, as well as a cellular protein which is recognised by them - the tumor suppressor Rb. We intend to examine several viral oncoproteins which target Rb; one is a protein (E7) from the Human Papilloma Virus which has been frequently associated with cervical carcinomas and other cancers. Accordingly, the results may have direct application to viral-induced cancer, and our work may lead to understanding of the regulation of protein transport to the nucleus. This may thus afford a new approach at the pharmacological level to combat transformation.Read moreRead less