Plasmids are extra mini-chromosomes that are present in many bacteria. They carry information that enables their hosts to survive and prosper in hostile environments. Plasmids are able to spread rapidly between bacteria, ensuring that the information they carry is rapidly disseminated throughout bacterial populations. Many plasmids carry information that increases the virulence of their host bacteria, because it adds to their repertoire of toxins and other adjuncts to invasiveness and colonisati ....Plasmids are extra mini-chromosomes that are present in many bacteria. They carry information that enables their hosts to survive and prosper in hostile environments. Plasmids are able to spread rapidly between bacteria, ensuring that the information they carry is rapidly disseminated throughout bacterial populations. Many plasmids carry information that increases the virulence of their host bacteria, because it adds to their repertoire of toxins and other adjuncts to invasiveness and colonisation, or enables them to survive in the presence of antibiotics. The emergence of multi-drug resistant bacteria and the rapid spread of the ability of bacteria to withstand most antibiotics available to date were mediated by plasmids. Plasmids also carry information that ensures their own survival. The consequence of this is that their bacterial hosts retain the plasmids, even when it is no longer beneficial to do so. For example, plasmids carrying information for resistance to antibiotics are not lost when their bacterial hosts grow in the absence of antibiotics. This is because plasmids have control systems, which ensure that on the one hand, replication of the plasmid keeps pace with the replication of its host, and on the other hand that the plasmid does not produce so many copies of itself that it overwhelms its host. This project examines the intricate regulatory system that a group of antibiotic-resistance plasmids uses to ensure that on average each plasmid molecule is replicated once per bacterial cell cycle. This system uses an antisense RNA, a tertiary RNA structure (pseudoknot) that acts as a translational switch, and a protein that interacts with different sequences on the plasmid to initiate replication. Detailed knowledge of the processes underlying this complex system is required if we are to develop new treatments that will lead to elimination of antibiotic-resistance and virulence-contributing plasmids from populations of pathogenic bacteria.Read moreRead less
Analysis Of HIV Virologic Response-rebound Data: Prognostic Indicators Of Post-HAART Viral Control
Funder
National Health and Medical Research Council
Funding Amount
$144,000.00
Summary
The introduction of potent anti-retroviral therapy into standard clinical management of HIV infected individuals has been associated with high rates of reduction in plasma viral loads over short periods of time. However, there remains considerable variation in the degree of longer-term viral control as a result of viral resistance, toxicity, timing of treatment initiation and choice of drug regimen. In particular, the most appropriate time to initiate treatment remains clouded, with the need to ....The introduction of potent anti-retroviral therapy into standard clinical management of HIV infected individuals has been associated with high rates of reduction in plasma viral loads over short periods of time. However, there remains considerable variation in the degree of longer-term viral control as a result of viral resistance, toxicity, timing of treatment initiation and choice of drug regimen. In particular, the most appropriate time to initiate treatment remains clouded, with the need to initiate treatment sufficiently early in order to avoid irreversible damage balanced by the problems of potential viral resistance or toxicity if started too soon. Determination of factors which will assist practitioners to optimise the timing of treatment initiation remains a high priority. Our aim in this project is to develop and study the use of novel statistical mixed-effects models designed to analyse factors associated with visit-time viral load data following commencement of therapy, taking account of the entire follow-up profiles of responses over time. The project involves both theoretical and empirical analyses of the estimation and inferential properties of the mixed-model method in conjunction with comprehensive analyses of prognostic factors associated with post-treatment virologic control in patients from the Western Australian HIV Cohort Study. These include demographic, virologic, immunologic, adherence and host genetic factors. The statistical methods developed will have wide applicability and add significantly to the suite of procedures available for the analysis of longitudinal response data.Read moreRead less
Hepatitis C Virus infects 3% of the world's population causing recurring liver disease, cirrhosis and hepatocellular carcinoma. To infect a liver cell, the viral glycoproteins attach to cell surface molecules wher they are activated to mediate merger of the viral and cellular membranes. This project grant will explore how the viral glycopropteins become activated and obtain essential structural information on the viral glycoproteins. These studies will help us to design antiviral agents.