Genome Wide Investigations Of Mycobacterium Tuberculosis To Reveal Processes Of Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$396,341.00
Summary
Tuberculosis remains a global health burden of staggering proportions. Around 1 in 3 people are infected with Mycobacteria tuberculosis, the organism responsible for the disease, which kills 2 million people annually. The emergence of strains now resistant to almost all of our front line drugs has placed extra pressure on researchers who are attempting to develop new protective vaccines and the critical antibiotics required to eradicate the disease. Furthermore the current global HIV pandemic is ....Tuberculosis remains a global health burden of staggering proportions. Around 1 in 3 people are infected with Mycobacteria tuberculosis, the organism responsible for the disease, which kills 2 million people annually. The emergence of strains now resistant to almost all of our front line drugs has placed extra pressure on researchers who are attempting to develop new protective vaccines and the critical antibiotics required to eradicate the disease. Furthermore the current global HIV pandemic is making the situation far worse as HIV kills the very cells of the body that protect us from tuberculosis. This research project will fill the significant gaps in our knowledge of M. tuberculosis infection, specifically identify the genes of the organism which allow it to invade and spread throughout the body. M. tuberculosis infection consists of 3 characteristic stages, i.e. colonisation, spread and long term survival in specialised structures called granulomas. It is from these granulomas that the bacterium can emerge after long periods of inactivity to cause clinical tuberculosis. Using a mouse model of infection I will define the genes needed by the bacterium to survive at these 3 key stages of disease thereby providing for a better knowledge base from which to design new vaccine strategies and to create effective drugs.Read moreRead less
Molecular Epidemiology And High Resolution Surveillance Of Salmonella Enterica Serovar Typhimurium In Australia
Funder
National Health and Medical Research Council
Funding Amount
$583,180.00
Summary
Salmonella typhimurium is a leading cause of the food-borne disease – salmonellosis. It is responsible for considerable morbidity and has an enormous economic cost. Molecular typing is the key to rapidly identify and control outbreaks. This project will employ next generation sequencing technology to develop a new molecular typing scheme. A surveillance system that integrates molecular typing data and epidemiological data will be developed for outbreak investigation and disease prevention.
Optimising Temporal Genomic Surveillance Of Salmonella Infections In Australia
Funder
National Health and Medical Research Council
Funding Amount
$763,447.00
Summary
Salmonella is a leading cause of the food-borne disease – salmonellosis. It is responsible for considerable morbidity and has an enormous economic cost. Molecular typing is the key to rapidly identify and control outbreaks. This project will optimise the use of whole genome sequencing for outbreak investigation and long term epidemiology. A surveillance system that integrates genome sequence and epidemiological data will be highly significant for outbreak investigation and disease prevention.
Improving The Understanding And Management Of Important Human Bacterial Infections
Funder
National Health and Medical Research Council
Funding Amount
$204,196.00
Summary
This project will focus on two important bacteria, Staphylococcus aureus (Golden Staph), and Enterococcus faecium, both causes of serious infections in hospital and community patients in Australia. Using new technologies, including whole genome sequencing, this project will lead to significant advances in understanding how these bacteria evolve, spread and cause disease. This will lead to new strategies for prevention and management of infections caused by these important bacteria.
Inhibition Of Haemostasis As A Novel Host-directed Therapy For Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$528,471.00
Summary
Mycobacterium tuberculosis-induced vasculopathy is an important cause of stroke worldwide, and stroke is a common (~20%) complication of tuberculous meningitis, the most dangerous presentation of tuberculosis. Blood clotting may also speed the growth tuberculosis in the body further worsening the situation. We will use zebrafish find out if clotting can be targeted to slow the growth of mycobacteria and then translate our findings to a mouse model of pulmonary tuberculosis.
Molecular Mechanisms Of Persistence Of Mycobacterium Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$398,142.00
Summary
Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB. It infects about third of all people in the world and kills several million people each year. People with active TB spread the mycobacteria in aerosols from their breath. When another person inhales an infected aerosol the mycobacteria enter their lungs and establish a new infection. During the course of infection M. tuberculosis is exposed to a variety of harsh environments inside the lungs which normally kill other bacte ....Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB. It infects about third of all people in the world and kills several million people each year. People with active TB spread the mycobacteria in aerosols from their breath. When another person inhales an infected aerosol the mycobacteria enter their lungs and establish a new infection. During the course of infection M. tuberculosis is exposed to a variety of harsh environments inside the lungs which normally kill other bacteria. M. tuberculosis is able to survive and adapt to those harsh environments. M. tuberculosis has an especially thick and tough cell wall which protects it. M. tuberculosis can adapt to the environments it encounters in a patient by changing their cell walls. The wall also protects mycobacteria from chemicals so it is resistant to many common antibiotics. There are some drugs to treat TB however M. tuberculosis is building up resistance to those drugs so we need to find new ones We will determine how mycobacteria synthesize their special cell wall and how they adapt during an infection. If we know how the details of how M. tuberculosis protects itself then we can find potential weakness which could be targets for the development of new drugs to treat TB.Read moreRead less
Acinetobacter Baumannii Virulence From A Regulatory Perspective: The Role Of Two Component Signal Transduction Systems
Funder
National Health and Medical Research Council
Funding Amount
$608,731.00
Summary
Acinetobacter baumannii is becoming a significant pathogen in the hospital and more recently in the community. It is very resistant to removal from surfaces and upon entering the host is almost impossible to treat with currently available antibiotics. It causes a wide range of disease states from wound infections and pneumonia to bacteraemia; little is known of this process. This research will increase our understanding of the disease process, providing possible treatment options in the future.
Structure And Functional Characterisation Of AB5 Toxins
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
The proposed research program, using a combination of structure and biochemical analyses, will provide insight into two novel AB5 toxins that represent a medically important family of proteins. This study will not only improve our fundamental understanding of AB5 toxins action but could lead to rational design of antimicrobials.
Role In Disease Of A Novel Epigenetic Regulator Associated With The Hypervirulent Neisseria Meningitidis Clonal Complex 41/44
Funder
National Health and Medical Research Council
Funding Amount
$403,249.00
Summary
Neisseria meningitis is a major cause of meningococcal septicaemia and meningitis worldwide. We have identified a phase variable DNA methyltransferase present in disease isolates, some of which have caused meningococcal epidemics. This methyltransferase is involved in the regulation of proteins involved in infection and disease processes. We will investigate whether this regulation increases the ability of the bacteria to adapt to changing host environments and cause disease.
Understanding Virulence Of Invasive Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$772,711.00
Summary
Staph aureus (Golden staph) is a major cause of disease in humans. In this project we will use state-of-the-art molecular biology and genomics to fully understand the mechanisms of virulence in this pathogen. This information will inform future approaches to development of therapeutics, as well as the use of genomics in clinical microbiology and disease management.