HIV infection is a dynamic process, in which the host immune response tries to control viral growth and keep up with the rapid evolution of the virus. This project assembles an interdisciplinary team of mathematicians and biologists to use a modelling approach to understand the dynamics of viral infection, viral evolution, and immune control in the infected individual. The insights gained from this project will help in the development of new drug and vaccination strategies.
Interactions Between Integrative Genomic Islands And Plasmids; Role In The Spread And Loss Of Antibiotic Resistance And Pathogenicity Determinants
Funder
National Health and Medical Research Council
Funding Amount
$776,465.00
Summary
Mobile elements that integrate into bacterial chromosomes at a specific site contribute pathogenicity and antibiotic resistance determinants to their bacterial host but only a few are able to move themselves into new hosts. Some plasmids and some elements can help certain others. In this project, genetic approaches will be used to investigate how plasmids and integrative elements help one another move into a new bacterium or compete with one another to stay in the same cell.
Herpesviruses infect most Australians and cause recurrent ulcers, birth defects and cancer. Infection lasts lifelong, and spreads to close contacts without obvious clinical signs. Thus disease is hard to prevent. However we can learn much from related animal infections. We have shown that both mouse and human herpesviruses enter mice via cells in the nose. Thus human infections might follow the same route. We will define what body defences work here and whether vaccines can prevent infection.
Human ?-herpesviruses persist for life, cause cancers and emerge with particular virulence when the immune system is weak. Vaccination against them is therefore an important health priority. We have shown for a related ?-herpesvirus of mice that live vaccines protect. Antibody seems to play a major role. We will test whether safer, recombinant vaccines are also sufficient to elicit protective antibody. Thus we can establish a viable strategy for preventing virus-induced human cancers.
Understanding The Role Of SSB1 In Embryonic Development And Genome Maintenance
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
Normally DNA exists as a double helix where two strands are zipped together. When single-stranded (ss) DNA is exposed during various cellular processes it can be easily damaged and degraded by cellular enzymes, but is protected by ssDNA binding proteins (SSBs). We have identified two new SSBs (SSB1 and SSB2) that play a crucial role in DNA repair and will investigate the role and physiological function of these important proteins.
Viral infections of the gut are one of the most debilitating infections one can suffer from. Noroviruses are the most common causative agents of viral-associated gastroenteritis but unfortunately little is known regarding their biology and pathogenesis. Our study aims to investigate the replication and pathogenesis of a mouse norovirus to shed light on similar aspects relating to human norovirus infection. We aim to understand how virus infection in cells leads to disease symptoms.
Immunoglobulin Germline Genes, BCR Repertoire Development And Disease Susceptibility. An Investigation Of Haplotypic Variation Between Individuals
Funder
National Health and Medical Research Council
Funding Amount
$519,828.00
Summary
The immune system is capable of making a repertoire of protective antibodies including literally tens of millions of different specificities. These are produced by permutations and combinations of a small set of ‘germline’ genes. This project will analyse how individual variations in the germline genes lead to individual differences in the repertoires of available antibodies, and will investigate whether or not such differences contribute to our susceptibility to infection and autoimmune disease ....The immune system is capable of making a repertoire of protective antibodies including literally tens of millions of different specificities. These are produced by permutations and combinations of a small set of ‘germline’ genes. This project will analyse how individual variations in the germline genes lead to individual differences in the repertoires of available antibodies, and will investigate whether or not such differences contribute to our susceptibility to infection and autoimmune diseases.Read moreRead less
Directed Evolution Of AAV Capsid Variants For Enhanced Targeted Genome Editing In The Human Liver
Funder
National Health and Medical Research Council
Funding Amount
$386,012.00
Summary
Liver transplantation is often the only treatment option available for patients with severe liver disease, and is complicated by a shortage of donor organs and the need for life-long drug therapy to prevent rejection. Repair of a patient’s own liver by gene therapy is a promising alternative. This project focuses on developing the technology required to undertake precise correction of genetic spelling errors in diseased liver cells without the need to first remove them from the body.
Influenza A Virus PB1-F2 Protein: A Putative Virulence Factor And Initiator Of Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$474,718.00
Summary
Influenza virus produces a protein of undefined function called PB1-F2. Infection of mice with virus expressing PB1-F2 from virulent strains causes severe lung inflammation, while PB1-F2 from milder seasonal viruses does not. We will examine how PB1-F2 influences virulence of human influenza in the ferret, which exhibits the same illness as humans. This work will help understand the disease severity of newly evolved influenza viruses of humans and the role of PB1-F2 in mediating this.
Understanding HIV Resistance To Entry Inhibitors To Advance The Development Of Novel Antivirals
Funder
National Health and Medical Research Council
Funding Amount
$877,585.00
Summary
We cannot afford to be complacent in the search for improved anti HIV drugs for 2 principal reasons; First, worldwide a staggering 66% of infected individuals who need treatment are still unable to access therapy; and Second, the main reason why most treated patients are now living longer and more healthy lives is because we have never stopped developing newer therapies to provide options for patients. In this study we will develop and test newer drugs that block HIV infection of cells.