Glycan-glycan Interactions Between Bacterial Pathogens And Host Cells: A Novel Mechanism Of Bacterial Adherence, A New Opportunity For Strategies To Treat And Prevent Disease And A New Paradigm In Interactions Between Macromolecules.
Funder
National Health and Medical Research Council
Funding Amount
$1,059,344.00
Summary
Cell surface carbohydrates are ubiquitous throughout nature. Human cell surface carbohydrates are specifically targeted by microbial proteins. These interactions are crucial in causing disease. We have recently shown that the carbohydrates on our cells and those on pathogenic bacteria can interact with one another. Understanding the nature and role of these newly discovered interactions may lead to strategies to block them via new drugs and vaccines.
The Identification Of Novel Diagnostics And Therapeutics From Bacterial Viruses Specific For The Foodborne Pathogen Campylobacter Jejuni Using Mass Spectrometry.
Funder
National Health and Medical Research Council
Funding Amount
$313,788.00
Summary
Campylobacter jejuni is the leading cause of foodborne illness within Australia. To improve food safety there is a critical need for new therapeutics and diagnostics that target this agent. Within nature bacterial viruses possess proteins that can perform such a task. By using mass spectrometric analysis we aim to exploit billions of years of co-evolution to identify bacterial viral proteins that bind C. jejuni to identify novel means to limit and lower C. jejuni numbers in food sources.
There is an urgent need to develop new drugs to treat human leishmaniasis, a disease that causes debilitating and life-threatening diseases in millions of people worldwide. This project will investigate whether it is possible to develop a new generation of drugs that target a novel metabolic pathway in these parasites that we have shown to be essential for virulence.
How Sweet It Is: Diagnostic Clinical And Experimental Glycoproteomics
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
Most human proteins are modified by the addition of complex sugar groups, which are important for the correct function of these key biological molecules. This fellowship will develop a suite of robust mass spectrometry glycoproteomic analytics for use in conjunction with clinical cohorts, model systems and in vitro biochemistry to investigate fundamental aspects controlling N-glycosylation in disease and translation to clinical diagnostics.
Defining The Role Of Glycosylation In Basement Membrane Failure During Muscular Dystrophy
Funder
National Health and Medical Research Council
Funding Amount
$824,664.00
Summary
This project aims to utilize mutations within the zebrafish fkrp gene to understand the pathogenic basis of the human diseases associated with mutation of this gene which results in a spectrum of muscular dystrophies. By generating models of alleles that represent the range of phenotypes seen in humans we will have a directly translatable model system to human pathology.
Blood Group Antigen Recognition By Group A Streptococcus Mediates Host Colonisation
Funder
National Health and Medical Research Council
Funding Amount
$470,821.00
Summary
Group A streptococcus (GAS) is responsible for approximately 700 million cases of localised infection and 600,000 cases of invasive infection globally each year. Certain bacteria have been shown to recognise sugars (known as glycans) on host cells. This project will look at how GAS use sugars at the surface of host cells to initiate disease, and determine if differences in the types of sugars present on host cells alter the ability of GAS to initiate infection.
The Glyco-interactome Of Pathogenic Neisseria: Understanding Disease And Defining Vaccine Targets
Funder
National Health and Medical Research Council
Funding Amount
$431,012.00
Summary
In order to infect humans and cause disease, many bacteria rely on interactions with carbohydrate (sugar) structures on human cells. This project aims to characterise the sugar interactions that enable Neisseria meningitidis (causes meningitis, sepsis) and Neisseria gonorrhoeae (causes gonorrhoea, associated with infertility and increased transmission of HIV) to cause disease. This will increase our understanding of host-pathogen interactions and aid development of new vaccines and therapeutics.
Targeting Glycointeractions To Generate New Opportunities To Treat And Prevent Bacterial Infections.
Funder
National Health and Medical Research Council
Funding Amount
$774,540.00
Summary
Bacteria and bacterial toxins can interact with complex sugar structures on human cells called glycans. My research team has identified new and important glycan interactions used by bacteria that cause diseases ranging from pneumonia, meningitis and food borne infections to urinary tract and sexually transmitted diseases. Now that these interactions have been discovered, they can be exploited to create drugs and vaccines that may treat and prevent disease by blocking the glycan interactions.
Role In Disease And Vaccine Potential Of Cell Surface O-linked Glycoproteins In Pathogenic Neisseria.
Funder
National Health and Medical Research Council
Funding Amount
$212,347.00
Summary
Bacteria that have adapted to life exclusively in the human host have developed unique strategies to colonize the host and to evade the immune response. An emerging strategy is modification of bacterial surface proteins with sugars or other modifications. Our data suggests a key role for these modifications in disease. We will investigate how the modifications are made, discover structures of novel modifications and determine their precise role in disease.