Understanding The Role Of NS Segments In Evading Influenza A Virus-specific Humoral And T Cell Immunity
Funder
National Health and Medical Research Council
Funding Amount
$213,812.00
Summary
Influenza viruses developed two ways to survive against host immune response: (i) mutating in its genes to escape host immune response, which may cause a new pandemic; (ii) using its NS1 protein to impair host immune response. However, little is known on how these two processes occur and whether NS1 could influence the outcome of escape mutants. By using virological and immunological methods, this study will show how viruses use different NS1 to enhance the viral escape mechanism.
Structural Determinants Of Siah Ubiquitin Ligase Complexes
Funder
National Health and Medical Research Council
Funding Amount
$267,750.00
Summary
Controlled degradation of cellular proteins is an important process. The turnover of proteins is a fine balance between protein expression and degradation and alterations can control many cellular processes such as mitosis and intracellular signaling. Whilst a lot of research has been directed at understanding protein expression in response to stimuli such as hormones, stress etc. little has been known about the mechanisms for targeting protein degradation. In recent years it has been shown that ....Controlled degradation of cellular proteins is an important process. The turnover of proteins is a fine balance between protein expression and degradation and alterations can control many cellular processes such as mitosis and intracellular signaling. Whilst a lot of research has been directed at understanding protein expression in response to stimuli such as hormones, stress etc. little has been known about the mechanisms for targeting protein degradation. In recent years it has been shown that proteins can be modified by the addition of a signaling protein called ubiquitin, and it is this modified form that is recognised for degradation. The degradation of these proteins occurs within a large protein complex called the proteasome, which recognizes the ubiquitinated protein substrates. The ubiquitination of proteins is a multistep process, the final step of which is catalyzed by a ubiquitin ligase, or E3 enzyme. It is the E3 which is able to recognize the protein to be degraded, and catalyze the transfer of ubiquitin onto that protein. The E3 proteins (or sometimes complexes) are a diverse group which have to recognize many different proteins, in order that they be degraded at appropriate times. We have been working on the protein Siah (seven in absentia homologue), a member of an E3 complex and important in controlled cell death, cell division and inflammatory responses. One part of the Siah protein is involved in binding proteins and targeting them for ubiquitination, though it is not known how Siah recognizes its targets. Using protein crystallography we have solved the 3D structure of this part of Siah and now propose to co-crystallize Siah with target proteins and binding partners so as to understand how Siah recognizes these proteins. Understanding the basis of these interactions will allow us to determine other potential targets for the Siah protein and also how we may be able to interfere with these interactions with therapeutic drugs.Read moreRead less
Modulation Of Leishmaniasis By The Proinflammatory Cytokines TNF
Funder
National Health and Medical Research Council
Funding Amount
$288,911.00
Summary
We have established a mouse model that has been genetically modified and cannot produce the cytokine tumour necrosis factor. This cytokine is secreted in the beginning of the inflammatory response. If these mice are infected with a parasite they are not able to heal the infection and die quickly. We can demonstrate that these mice cannot regulate the beginning inflammatory response and do not form a cellular infiltrate at the site of infection.
Understanding Respiratory Infections To Improve Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$268,497.00
Summary
Indigenous children have the highest rates of ear disease (OM) and associated hearing loss in the world. Papua New Guinea has the highest child mortality rates in the Western Pacific Region with 23% of deaths from pneumonia. OM and pneumonia vaccines can be improved through broadening their coverage of disease-causing pathogens. This study will identify the pathogens that currently cause OM in Indigenous children and pneumonia in PNG, and will measure the immune responses to these pathogens, in ....Indigenous children have the highest rates of ear disease (OM) and associated hearing loss in the world. Papua New Guinea has the highest child mortality rates in the Western Pacific Region with 23% of deaths from pneumonia. OM and pneumonia vaccines can be improved through broadening their coverage of disease-causing pathogens. This study will identify the pathogens that currently cause OM in Indigenous children and pneumonia in PNG, and will measure the immune responses to these pathogens, in order to develop improved vaccines.Read moreRead less
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.
Discovering Novel Molecules That Regulate Axonal Degeneration.
Funder
National Health and Medical Research Council
Funding Amount
$588,622.00
Summary
The axon is the primary signaling component of every neuron and is essential for normal function. Axonal degeneration is a key early pathological hallmark of Alzheimer’s disease. We lack a basic understanding of molecules that regulate this process. Such knowledge is essential for the development of treatments and therapies for dementia and the preservation of healthy ageing. I aim to discover the molecules that regulate axonal degeneration and study their function.