Inhibition Of Cellcell Actin-based Motility During Poxvirus Infection By The Kinase Inhibitor Glivec
Funder
National Health and Medical Research Council
Funding Amount
$92,950.00
Summary
Although smallpox, one of the deadliest human pathogens, was eradicated in 1980, the current global climate has resulted in fears that smallpox may be used as a biological weapon. Unfortunately the smallpox vaccine poses a serious health hazard to certain people. We have shown that Glivec, a drug used to treat cancer, has potent anti-viral affects on poxvirus replication. This project will test the effectiveness of Glivec in treating smallpox in an animal model and study how it acts.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
Structural And Functional Analysis Of A Cancer-linked Co-regulator Complex
Funder
National Health and Medical Research Council
Funding Amount
$729,571.00
Summary
We seek to understand the mechanisms by which genes are switched on and off throughout our lifetime. A number of multi-component protein machines are involved in this process but their make-up and mechanism of action is not understood. We will investigate the structure and function of one of these machines that has been strongly linked to cancer.
Translational Research Initiatives In Acute Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Recent research has focussed on molecular characterisation of high-risk acute leukaemia subtypes. This proposal will combine the power of genomic analysis, global analysis of protein kinases and stringent preclinical drug testing in order to improve the treatment of these high-risk acute leukaemia subtypes. Several innovative and interrelated projects within this Program will utilise a unique and clinically relevant experimental model to achieve their goals.
Prion-like Behaviour In Immunity: Super-sized Signalling Platforms?
Funder
National Health and Medical Research Council
Funding Amount
$611,995.00
Summary
Prions have been mostly associated with pathologies but recent discoveries show that prion-like behaviour may be beneficial, enhancing our immune response for example. To test this, we want to systematically explore all human proteins involved in the defence against pathogens, find new prion-like trends and probe their role in the innate immune response.
A New Model For The Pathogenesis Of Rheumatic Fever: Superantigen Priming Of The Immune Response To Group A Streptococci
Funder
National Health and Medical Research Council
Funding Amount
$248,820.00
Summary
Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, c ....Acute rheumatic fever (ARF) is now rare in developed countries. However, it remains a major problem in Aboriginal Australians in the NT where the rate of ARF is the highest in the world. This leads to high rates of rheumatic heart disease (up to 3% of individuals in some communities) and a premature mortality of over four times that for developing countries. Immunisation and improved living conditions offer a long-term solution but these remain a distant prospect. In the short and medium term, control of this ARF will partly depend on new and better treatment and prevention strategies. To achieve these goals a deeper understanding of the immune mechanisms underlying this disease is urgently needed. It is known that ARF is caused by an abnormal immune response following streptococcal infection. This leads to the production of cells called T cells that attack the body s own tissues rather than the bacteria itself. This autoimmune disease is responsible for the heart damage that underlies ARF. It is believed that this proces only occurs when susceptible individuals are infected with specific rheumatogenic strains of streptococci. However there are a number of deficiencies in this model and it is proposed that there is an additional factor responsible for the abnormal immune response in ARF. This project will explore the possibility that bacterial toxins called superantigens are the critical missing factor , by studying the immune response in ARF. Superantigens are produced by certain streptococci and staphylococci, and are potent in minute quantities causing widespread activation of the immune system. They have been found to play an important role in a number of autoimmune diseases and the type of immune response found in ARF fits well with that expected if superantigens were involved. If superantigens play an important role in causing the abnormal immune response in ARF then a number of new avenues would open for the treatment and prevention of this disease.Read moreRead less
Structural And Functional Studies On RNA Nuclear Retention Mediated By Paraspeckles: A Novel Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$290,978.00
Summary
Dynamic interactions between proteins and nucleic acids are essential process in gene regulation, where aberrant regulation leads to various diseases including cancers. The project aims to examine the interactions between paraspeckle proteins and nucleic acid molecules via determination of the structures of protein-nucleic acid complexes at the atomic level. The results will provide a better understanding of a recently discovered gene regulation mechanism and a basis for new gene therapy.
Invasive fungal infections are a serious, escalating health issue. They cause severe disease with high death rates and are very costly to the health system. Current drugs often have suboptimal efficacy and cause side effects. New drugs are needed urgently. Many fungi, including the AIDS-related pathogen, Cryptococcus neoformans, secrete phospholipase B (Plbp) to facilitate infection. We will identify and investigate the Plbp secretion pathway as a novel anti-fungal drug target.