The Molecular Basis Of Bacterial Infectious Diseases
Funder
National Health and Medical Research Council
Funding Amount
$16,230,996.00
Summary
Bacterial infectious diseases are a serious threat to human health, accounting for over 10 million deaths each year. This multidisciplinary collaborative team is investigating the complex interactions between major disease-causing bacteria and their human hosts, in order to determine how they cause disease. These studies will make a major contribution to fundamental knowledge in this field. This information is also essential for the development of cheaper and more effective vaccines, as well as ....Bacterial infectious diseases are a serious threat to human health, accounting for over 10 million deaths each year. This multidisciplinary collaborative team is investigating the complex interactions between major disease-causing bacteria and their human hosts, in order to determine how they cause disease. These studies will make a major contribution to fundamental knowledge in this field. This information is also essential for the development of cheaper and more effective vaccines, as well as novel drugs. These are urgently needed to reduce death and illness due to bacterial infectious diseases in the 21st century. 11Read moreRead less
Functional Genomics Of Malaria Liver Infection And Transmission
Funder
National Health and Medical Research Council
Funding Amount
$470,144.00
Summary
Chemotherapy is the front line defense against malaria but resistance is emerging. The WHO has advised that new drugs should target parasite stages that perpetuate the transmission of malaria to break the cycle of infection. We have identified proteins that are essential for the two transmissive stages of the most deadly parasite to infect their hosts. We will determine the precise function of these proteins and the mechanisms they govern. This may guide the development of new interventions.
Antibiotic resistance is a looming public health crisis. New antibiotics with new mechanisms of action are desperately needed. The long-term goal of this research is to develop new drugs that disarm bacteria to overcome the problem of antibiotic resistance.
ROLE OF RIP KINASES & IAPs IN MUCOSAL IMMUNE DEFENCE
Funder
National Health and Medical Research Council
Funding Amount
$631,168.00
Summary
Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes in ....Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes infection.Read moreRead less
Infectious diseases plague mankind; with infections responsible for approximately 20% of all deaths worldwide. New strategies are urgently needed and we have positioned our research to address questions around how to forestall bacterial pathogens in the initial phases of invasion of human tissues and provide full understanding of the key molecules on the surfaces of bacterial cells. This fundamental knowledge is crucial to new drugs, vaccines and infection-resistant medical devices.
This program will investigate the strategies used by pathogenic bacteria to cause human diseases. The research will focus on how bacteria initiate infections, how they invade, cause cell and tissue damage and respond to their human host. It will also examine how the host’s innate immune system interacts with these bacteria. The results will provide new insights into host-pathogen interactions and reveal new targets for the development of novel antibacterial drugs and vaccines.
Function And Inhibition Of Plasmepsin V In Targeting Malaria Virulence Proteins Into Human Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$407,845.00
Summary
Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cel ....Malaria parasites dramatically renovate infected erythrocytes to survive and evade the host immune system by delivering hundreds of exported parasite proteins into the cell. The parasite protease Plasmepsin V is essential for protein export. We aim to develop potent inhibitors of this protease in the hope of blocking its function and killing the parasite. We also aim to discover the components of the trafficking pathway after cleavage by Plasmepsin V that sorts virulence proteins to the host cell.Read moreRead less
Integrating Immunity And Genetics In Follicular Lymphoma To Establish A Prognostic Score Fit For The Modern Era
Funder
National Health and Medical Research Council
Funding Amount
$1,377,174.00
Summary
Follicular lymphoma (FL) is divided into early and advanced stages. Early stage FL is frequently cured, but there is no way to identify who will be cured and who won't. By contrast advanced stage FL is incurable. Our unique access to well-annotated clinical trial and population based cohorts allows us to perform a detailed biological comparison of early and advanced FL, to gain a deeper understanding of the impediments to eradicating the disease, and to predict outcome to conventional therapy.
Development Of Therapeutically Useful Human Artificial Chromosomes For Gene Delivery And Optimal Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$496,986.00
Summary
Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in ....Gene therapy is an exciting new form of treatment for genetic disorders aimed at providing long-term correction of the problems at source - namely the affected gene. The biggest technical hurdle facing gene therapy is to be able to deliver the therapeutic genes efficiently and safely into patient cells. Many gene therapy protocols are currently being trialled clinically. These protocols, based mostly on the use of attenuated viruses to deliver the genes, carry potential risks to the patients in terms of infection, immune response, and germline modification. We have developed the first stage of a new technology for gene delivery that does not require the use of viruses. This technology is based on the generation of human artificial chromosomes, which are smaller versions of the naturally occurring chromosomes that carry all the genes inside our cells. Safety in these artificial chromosomes comes from the use of entirely human materials for their engineering. These artificial chromosomes also have other advantages over the viral approaches, including allowing large genes to be carried, and providing a permanent cure in a single treatment. We have already successfully constructed, published, and patented a number of first-generation human artificial chromosomes. The current project aims to complete the next proof-of-concept milestone towards the further development of this technology. Specifically, we propose to demonstrate the ability of the artificial chromosomes to carry genes and provide sustainable expression of these genes in cells and in animal models. Success in this study will allow the technology to proceed rapidly into commercialisation and clinical trial as a new improved tool for gene delivery and gene therapy.Read moreRead less
Discovering And Targeting Genes Regulating Skeletal Muscle Function, Metabolism, And Adaptations To Exercise Interventions
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Muscle wasting and decreased in mitochondrial function due to ageing or lack of physical activity are associated with reduced quality of life. The overarching aim is to develop a unique research program focusing on targeting specific genes, and to discover novel genes regulating muscle wasting and mitochondrial (dis)function. I anticipate this approach to assist in the development of targeted and personalised prevention and therapy for diseases associated with muscle (dis)function.