Molecular Characterisation Of Early Precursor Lesions Of A Novel Ñserrated Pathwayî Of Colorectal Cancer Using Gene Expression And Proteomics.
Funder
National Health and Medical Research Council
Funding Amount
$318,338.00
Summary
In Australia, CRC is the second highest cause of all cancer-related deaths. If detected early, CRC has a high success rate of cure, but a percentage of precursor lesions escape detection and show aggressive clinical behaviour to progress to CRC. These are difficult to diagnosis with existing technologies. We aim to understand the biology behind sessile serrated adenoma pathways and hence enhance early detection, diagnosis and treatments strategies.
Understanding The Pathogenesis And Heterogeneity Of Autoimmunity As Failure Of Multiple Steps
Funder
National Health and Medical Research Council
Funding Amount
$504,023.00
Summary
Autoimmune diseases like diabetes, thyroid disease or rheumatoid arthritis affect around 1 in 15 people in Australia. It is clear that defects in a number of different genetic mechanisms can contribute to the development of autoimmunity. But it is currently not clear how these different mechanisms need to interact to prevent the onset of disease. This grant seeks to understand these interactions and how defects in two or more tolerance mechanisms can lead to autoimmunity.
How Does NF-kB2 Regulate Thymic Selection To Prevent Organ-specific Autoimmune Disease?
Funder
National Health and Medical Research Council
Funding Amount
$787,600.00
Summary
Autoimmune diseases like type 1 diabetes and thyroiditis arise from defects that cause the immune system to confuse self and non-self. Normally, this distinction is programmed in the thymus. We recently identified the gene that causes a form of autoimmune disease. We also made an important discovery about how the thymus gland regulates self-non-self discrimination. We will build on these two discoveries to gain a precise understanding of how the immune system normally avoids autoimmune disease.
Epigenetic Programming Of Immune Development In Utero: Role Of The Maternal Environment In The Allergy Epidemic
Funder
National Health and Medical Research Council
Funding Amount
$764,463.00
Summary
This study will provide new insights into the development of allergic disease. Specifically, we will explore the hypothesis that allergic disease and other disorders or immune dysregulation occur as a result of gene-environmental interactions in early life, and that these events begin in pregnancy when the developing fetus is still developing and most susceptible to these effects.
The Relationship Between Maternal And Infant Dietary Intake Of Fermentable Fibre, Gut Microbiota, Short Chain Fatty Acids And Allergic Disease And Asthma: A Population-derived Birth Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$871,700.00
Summary
The proposed study will involve the Barwon Infant Study (BIS) cohort of 1074 infants to provide the first systematic investigation of the hypotheses that the epidemic of allergic disease and asthma in many parts of the world relates to the paucity of fermentable fibre in the modern diet, and that the protective effect of fermentable fibre is mediated by changes in the organisms that colonise the gut and the metabolites that they produce.
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
Methylation-sensitive T Cell Genes And Childhood Food Allergy.
Funder
National Health and Medical Research Council
Funding Amount
$461,232.00
Summary
Australia has the highest reported prevalence food allergy in the world. Despite this, little is known about how allergy develops. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of food challenge proven food allergy with assessment of immune functioning & cutting edge genomics, to extensively characterise the pathways leading to food allergy in children.
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.
Understanding The Role Of The Putative Phospholipid Translocase ATP11c In B Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$455,153.00
Summary
The immune system protects humans against recurrent infections with a wide range of pathogens. Formation of antibodies is a crucial element of the immune response. Defects in the production of antibodies can lead to recurrent and often life-threatening infections. This project seeks to understand a genetic defect in mice resulting in an almost complete absence of antibody producing cells, thereby causing a disease that is similar to some forms of human immunodeficiency.