Genotypes And Phenotypes Of Human Primary Non-congenital Antibody Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$544,692.00
Summary
Antibodies represent a key component of the immune system, and a particularly important in defence against bacterial and viral infections. In some individuals, antibody production fails, rendering them more susceptible to infection. In most cases, the mechanism of antibody failure is unknown. This project seeks to determine the genetic and cellular mechanisms of antibody failure. This could improve diagnosis for immune deficiency, and improve our overall understanding of the immune system.
It is feasible to sequence patient genomes but we need to know more about how genetic variants cause complex disease. We have sequenced genomes from patients with immune deficiency and will test the idea that genetic variation causes consistent changes in particular white blood cells, thus providing a bridge between genomic information and clinical diagnosis. Outcomes will include more accurate diagnosis, better understanding of immunity, and a strategy for using whole genome information.
Investigating B Cell Development, Maintenance And High-affinity Antibody Production By ENU Mutagenesis
Funder
National Health and Medical Research Council
Funding Amount
$408,388.00
Summary
B cells are essential for the protection against infections. This application aims to identify new genes that are crucial for the development or function of B cells and will investigate how mutations in newly discovered genes contribute to defects in the development and function of B cells and the pathogenesis of B cell leukaemia.
We have discovered a single tumour factor which causes cancer cachexia, a wasting condition that is one of the worst complications of malignancy, for which there is no current effective treatment. We have developed antibodies which effectively block this condition in preclinical models and have produced human/humanised version of this. This application is to characterise these human antibodies to allow us proceed to clinical trials.
Alpha-particles linked to recombinant antibodies targeting tumour cells have potential to effectively treat tumours while minimising normal tissue side effects. We will explore a novel alpha-particle therapy approach to solid tumours, by delivering 225Ac directly into tumour cells, or into cells that support the tumour (microenvironment). This approach will hopefully result in development of a new approach to treatment of cancers that are resistant to conventional therapies.
Heparin-induced Thrombocytopenia And Thrombosis: Better Understanding Of Pathogenesis And Improving Diagnosis And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$653,137.00
Summary
Heparin, a widely used drug, can cause an adverse effect which results in a fall of the platelet count and the development of serious thrombosis. This drug complication is mediated by an immune mechanism. This proposal aims to provide a better understanding of the disease mechanism. It also aims to develop a new test that will improve the diagnosis, and to produce a novel drug that will effectively suppress the immune reaction and improve the treatment.
Discovery Early Career Researcher Award - Grant ID: DE120102166
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Identification and characterisation of anti-viral immune response genes in mosquitoes. Emerging viral diseases, transmitted by mosquito bite, present an increasing public health risk globally. Most research to date has neglected the infection dynamic in the insect vector. This project aims to characterise the defensive response of mosquitoes to viral infection, a potentially crucial factor in the epidemiology of vector-borne disease.
From genotype to phenotype: Molecular photofitting for criminal investigations. DNA found at crime scenes has the potential to provide a physical description of the donor in the same way as an eyewitness statement can be used to make a facial reconstruction. This project will investigate those physical traits which can be derived from the analysis of DNA present in samples collected in relation to criminal activities.
Photosynthetic traits as “key performance indicators” of coral health. The objective of this project is to advance knowledge on the healthy functioning of the coral–algal symbiosis, which defines the response of coral reef ecosystems to worldwide environmental change. Current approaches to address this problem have linked coral health to algal symbiont diversity but have been unable to resolve the fundamental symbiont functional traits that govern this link – the “key performance indicators (KPI ....Photosynthetic traits as “key performance indicators” of coral health. The objective of this project is to advance knowledge on the healthy functioning of the coral–algal symbiosis, which defines the response of coral reef ecosystems to worldwide environmental change. Current approaches to address this problem have linked coral health to algal symbiont diversity but have been unable to resolve the fundamental symbiont functional traits that govern this link – the “key performance indicators (KPIs)”. This project plans to couple advanced physiological and functional genomics techniques to transform our understanding of how algal symbiont metabolic KPIs regulate coral growth and stress susceptibility. This may provide new diagnostic capability for the assessment of coral health and may enable us to improve coral reef ecosystem management.Read moreRead less
A NOVEL MOUSE MODEL TO INVESTIGATE THE MECHANISMS OF VIRUS-INDUCED ARTHRITIS
Funder
National Health and Medical Research Council
Funding Amount
$336,000.00
Summary
We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators ( ....We have developed a novel animal model by which to study arthritic disease caused by insect-transmitted viruses known as arboviruses. The existence of this model and novel reagents provides an excellent opportunity to further explore the basic mechanisms of infectious disease in a complete functioning animal, rather than specific cultured cells. The study will use modern approaches in molecular and cellular biology to achieve this goal. The production by our immune systems of soluble mediators (cytokines-chemokines) and antibodies is an overwhelming positive aspect of our physiological response to infection by microbes. Protection from disease by these immune compounds can happen naturally, or the body's ability to produce these factors can be exploited to our benefit via the administration of vaccines. However, these factors can also be detrimental to the host contributing to severe disease. For instance, work performed almost 40 years ago showed for the first time that under particular conditions, antibodies against viruses can enhance infection, instead of inhibiting infection as normally seen. In the intervening years work by scientists all over the world has associated antibody-dependent enhancement (ADE) of infection to many types of viruses; ADE is even thought to be a risk factor to serious disease with dengue virus, and has been shown in vitro for the AIDS virus and Ebola virus. We have recently discovered a molecular mechanism which explains how antibody enhances viral infection in vitro. In studies on immune cells infected with Ross River Virus (RRV) we found that infection helped by antibody resulted in the specific disruption to the production of cellular chemicals which are toxic to viruses. Are these mechanisms of antibody-enhanced infection also found in animals? Will such mode of infection cause enhanced disease and tissue pathology (arthritis) in animals?Read moreRead less