Legionella bacteria are the major cause of Legionnaire’s Disease, a common form of acute pneumonia. Here we will study how the bacteria avoid killing in human cells by establishing an intracellular niche that is sequestered from the normal host cell defence pathways. In particular we hope to understand how the bacteria regulate a major protein modification pathway called ubiquitination.
Interferon Mediated Control Of Legionella Infection
Funder
National Health and Medical Research Council
Funding Amount
$628,848.00
Summary
Bacterial lung infections are a serious cause of illness and death in humans. To fight infection the body activates the immune system using a network of signalling molecules. We are studying exactly how one of these signalling molecules called interferon controls the infection. Interferon induces the killing of bacteria that are replicating inside human lung cells. How interferon drives bacterial death is not known and this will be studied in this proposal.
Manipulation Of Clathrin-mediated Trafficking By Coxiella
Funder
National Health and Medical Research Council
Funding Amount
$667,857.00
Summary
This research will uncover how Coxiella causes the serious infectious disease Q fever by commandeering human cells and replicating to high numbers within a specialised vacuole. We will investigate virulence factors of Coxiella, learning how and why they target an essential human vesicular trafficking process. Our innovative approach and unique expertise will elucidate interaction between this pathogen and the human cell, providing fundamental knowledge towards public health outcomes.
How The Intracellular Pathogen Coxiella Burnetii Manipulates Host Small GTPases To Facilitate Disease
Funder
National Health and Medical Research Council
Funding Amount
$534,510.00
Summary
This study explores how the bacterium Coxiella burnetii causes the serious infectious disease Q fever. Coxiella is a potential biological weapon because it is stable in the environment and few organisms are required to cause disease. Coxiella is able to manipulate human cells to replicate in a unique location within the cell but little is known about how they do this. Here we will study the host proteins that are important during infection and how Coxiella manipulates these factors to facilitate ....This study explores how the bacterium Coxiella burnetii causes the serious infectious disease Q fever. Coxiella is a potential biological weapon because it is stable in the environment and few organisms are required to cause disease. Coxiella is able to manipulate human cells to replicate in a unique location within the cell but little is known about how they do this. Here we will study the host proteins that are important during infection and how Coxiella manipulates these factors to facilitate intracellular replication.Read moreRead less
Defining Pathogenic Mechanisms Of Intracellular Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$494,691.00
Summary
This study explores how the bacterium Coxiella burnetii causes the serious infectious disease Q fever. Coxiella is a potential biological weapon because it is very stable in the environment and few organisms are required to cause disease. Coxiella is able to commandeer human cells to replicate in a specialized vacuole but little is understood about how they do this. We will examine the virulence factors of Coxiella and investigate how they allow the bacteria to replicate inside human cells.
Killing Infected Cells As A Mechanism To Eradicate Tuberculosis
Funder
National Health and Medical Research Council
Funding Amount
$1,085,770.00
Summary
Mycobacterium tuberculosis (Mtb), the causative agent of TB, is rapidly becoming resistant to all antibiotics and this disease kills more than one million people each year. This underscores the urgent need to develop new treatments for this disease. We are developing a therapy that kills Mtb infected cells and may help to eradicate infection. This highly novel approach to the treatment of TB would have profound implications for the 2 billion people infected with this pathogen.
Bacterial Inhibition Of Cell Signalling And Apoptosis During Gastrintestinal Infection
Funder
National Health and Medical Research Council
Funding Amount
$542,011.00
Summary
E. coli are a major cause of severe diarrhoeal disease. In order to establish infection, E. coli inhibits a host response where cells with bacteria stuck to them are ‘killed off’ and excreted as waste. This recent discovery illuminated an unknown role for cell death in the immune response during bacterial gastroenteritis. This project will study this phenomenon further to better understand the host immune response to infection and also other gut diseases such as inflammatory bowel disease.
Host innate defence relies on the activation of several signalling pathways that regulate inflammation and cell death. Several important bacterial pathogens of humans inject virulence “effector” proteins into infected cells that interrupt host cell signalling pathways. We recently discovered a family of new effector proteins that directly degrade host proteins and block cell death. Here we will characterise this and other members of the family to understand their role during infection.
Death Receptor Signaling During E. Coli And Salmonella Infection
Funder
National Health and Medical Research Council
Funding Amount
$586,076.00
Summary
Upon encountering invading microorganisms, the body’s immune system usually initiates an inflammatory response to recruit populations of immune cells to the site of infection. To counter this attack, many bacterial pathogens have evolved distinct ways of disarming the inflammatory response. We are investigating the discovery that gastrointestinal bacteria such as Salmonella and pathogenic E. coli specifically interfere with the messages sent by the body’s innate sensors to recruit killer immune ....Upon encountering invading microorganisms, the body’s immune system usually initiates an inflammatory response to recruit populations of immune cells to the site of infection. To counter this attack, many bacterial pathogens have evolved distinct ways of disarming the inflammatory response. We are investigating the discovery that gastrointestinal bacteria such as Salmonella and pathogenic E. coli specifically interfere with the messages sent by the body’s innate sensors to recruit killer immune cells.Read moreRead less
Innate Immune Signalling In Mycobacterium Tuberculosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$562,857.00
Summary
Tuberculosis (TB) is a major global health threat that causes 1.5 million deaths every year. This study will characterise a new molecular control mechanism that optimises the immune response to the bacteria that cause TB and determine how it contributes to controlling the infection. Such knowledge is essential to help improve patient management and develop better treatments for this devastating disease.