Design And Engineering Of Adnectins For Diagnosis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$803,152.00
Summary
This project aims to engineer a naturally-occurring human protein, called an adnectin, to produce molecules that are able to bind specific targets in the human body, and as such may be used in the diagnosis and therapy of a range of diseases.
Colorectal Cancer Membrane Protein Interactomics [A Major Discriminator Of Clinical Outcome]
Funder
National Health and Medical Research Council
Funding Amount
$643,778.00
Summary
This project studies the molecular causes of colorectal cancer (CRC) malignancy because CRC is the 2nd most common malignancy by incidence and cause of death in the Western world. It currently results in 13.1% of Australian cancer deaths. The aim of this NHMRC project is to gain a detailed understanding of how particular cell membrane proteins interact with each to give cancer cells the ability to invade and spread.
Biochemical Analysis Of Akt 3-specific Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$349,375.00
Summary
The Akt family of enzymes consists of 3 protein kinases (Akt 1,2 and 3) and has been shown to regulate many normal cellular processes such as cell proliferation, growth, survival and motility, as well as the growth of new blood vessels. All these processes are critical for cancers to grow. However, few studies have distinguished the roles of the individual family members. Our preliminary data revealed Akt3 is far more active than the other two forms. Furthermore, using our unique Akt3 specific a ....The Akt family of enzymes consists of 3 protein kinases (Akt 1,2 and 3) and has been shown to regulate many normal cellular processes such as cell proliferation, growth, survival and motility, as well as the growth of new blood vessels. All these processes are critical for cancers to grow. However, few studies have distinguished the roles of the individual family members. Our preliminary data revealed Akt3 is far more active than the other two forms. Furthermore, using our unique Akt3 specific antibody, we find Akt 3 protein and activity levels are high in rapidly proliferating ovarian cancer cell lines and in primary ovarian tumours. The aim of this proposal is to characterise the mode and role of signalling via Akt3, including the identification of targeted substrates and signaling pathways and the outcomes of Akt3 driven signaling on cellular properties. These studies will provide important clues to understanding how this family member functions in both health and disease. Elucidation of the basis of Akt3 dependent signalling will open the possibility for the development of drugs that interfere with Akt3 function (for example in high Akt 3 expressing tumours like those of the ovary). In the long term, extension of our profiling studies to other tumour types will give a novel insight into the extent of Akt3 de-regulation as a key mediator of cancer formation.Read moreRead less
Novel Regulation Of RDNA Transcription By MTOR/S6K Signalling
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
Increased cellular growth requires a number of important processes to occur, the most fundamental of which is protein synthesis. Successful synthesis of proteins requires a large number of efficient ribosomes, the protein synthesis machinery. mTOR is a central cellular signalling molecule that directly regulates growth via modulating the efficiency of the ribosomes. It does this by regulating an enzyme called S6 kinase. Interestingly for long term or sustained increases in the rates of growth an ....Increased cellular growth requires a number of important processes to occur, the most fundamental of which is protein synthesis. Successful synthesis of proteins requires a large number of efficient ribosomes, the protein synthesis machinery. mTOR is a central cellular signalling molecule that directly regulates growth via modulating the efficiency of the ribosomes. It does this by regulating an enzyme called S6 kinase. Interestingly for long term or sustained increases in the rates of growth an increase in the number of ribosomes in addition to an increase efficiency of protein synthesis is required. This proposal will test the hypothesis that the mTOR-S6 kinase signalling pathway regulates protein synthesis both at the level of ribosome efficiency and capacity. This will be extended to determine the mechanism by which such regulation occurs. Furthermore recent studies have demonstrated that S6 kinase is involved in tumor growth. We propose that S6 kinase will contribute to the regulation of both normal or tumor growth at least in part via modulation of the number of ribosomes. Accordingly, S6K is upregulated in a segregated proportion of breast tumors. Outcomes from this project have the potential to provide targets to which specific therapies for particular breast tumors can be developed. Overall this information will also extend our basic knowledge on normal growth regulation.Read moreRead less
Biochemical And Molecular Dissection Of The Mechanisms Controlling Ribosome Biogenesis By The PI3K/AKT/mTOR/MYC Network
Funder
National Health and Medical Research Council
Funding Amount
$545,180.00
Summary
Ribosome synthesis and function are critical for normal cell growth and division and hence this process is exquisitely regulated. Conversely, de-regulated cell growth can lead to cancer. We have identified new roles for the AKT and SGK families of kinases in controlling this process. This proposal aims to establish the mechanisms by which these enzymes control ribosome synthesis to better understand growth control and to provide insight for targeting these pathways in growth driven cancers.
Protein Networks Mediating Copper Balance And Their Break-down In Disease.
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
Neurological disorders (eg. Alzheimer s, Parkinson s and prion diseases) impose a growing health burden on society. Exciting new therapeutic possibilities stem from the discovery that copper (Cu) plays a central role in the disease process. Our research will help foster a holistic understanding of the protein network regulating copper balance, particularly in the brain, and where it breaks down in disease. Clinical benefits include new targets for diagnosis and treatment of Cu-related diseases.
Insulin-regulated Aminopeptidase, Glucose And Memory
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
We have previously shown that inhibitors of IRAP improve performance in memory tasks in normal and memory impaired animals and are currently developing new treatments for memory loss using IRAP as a target. In this study, we will investigate the physiological roles of IRAP and its association with intracellular proteins. The knowledge obtained will provide insights of how the brain process memory and confirm the suitability of IRAP inhibitors as drugs for treating memory deficits.
Novel Therpeutic Approaches For Alzheimers Disease
Funder
National Health and Medical Research Council
Funding Amount
$604,734.00
Summary
There are currently no effective treatments for Alzheimer's disease. In this application we will develop a novel class of compound to assess their potential as AD therapeutics. These compounds will be tested in vitro and in vivo models of Alzheimer's disease. The successful conclusion of the work described here would provide new leads suitable for further development as therapeutics for Alzheimer's disease.
Production And In Vivo Delivery Of Bacteriphage Lytic Enzymes By Lactobacillus Fermentum For Disease Prevention.
Funder
National Health and Medical Research Council
Funding Amount
$272,250.00
Summary
Lactic acid bacteria are commonly found in the oral cavity, digestive and female urogenital tracts of humans and other mammals. They are almost completely harmless with only some streptococci and enterococci being able to cause disease. The harmless lactic acid bacteria are mainly classified as Lactobacillus or Lactococcus, and members of of these groups are used in the manufacture of dairy foods such as yoghurt and cheese. Lactobacilli in particular are marketed in a number of health-promoting ....Lactic acid bacteria are commonly found in the oral cavity, digestive and female urogenital tracts of humans and other mammals. They are almost completely harmless with only some streptococci and enterococci being able to cause disease. The harmless lactic acid bacteria are mainly classified as Lactobacillus or Lactococcus, and members of of these groups are used in the manufacture of dairy foods such as yoghurt and cheese. Lactobacilli in particular are marketed in a number of health-promoting or probiotic foodstuffs which are consumed all over the world. We are interested in developing lactobacilli into therapeutic agents which will prevent or treat infections caused by a range of harmful bacteria including the bacteria which cause strep throat and food poisoning. Lactobacilli will be genetically modified to produce enzymes which specifically kill harmful bacteria. These enzymes are from viruses which infect specific bacteria. Using animal models the modified lactobacilli or lactobacilli produced enzymes will be administered orally and tested for their ability to treat possible infections caused by pathogenic bacteria in the oral cavity and intestine. This new therapeutic production and delivery system offers an alternative infectious disease control method to antibiotics. This agent may also be used to control some of the antibiotic-resistant bacteria that are of significant worldwide concern.Read moreRead less