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.
Modeling Human Actin Related Protein 2/3 Complex Subunit 1B (ARPC1B) Deficiency In Mice
Funder
National Health and Medical Research Council
Funding Amount
$755,005.00
Summary
The actin cytoskeleton forms the structure that not only keeps cells in their normal shape but is also essential for the movement of cells and for interaction between cells. We have recently identified the first patients with an immunodeficiency caused by a defect in a gene called ARPC1B, which plays a crucial role in the regulation of actin. Through the investigation of novel mouse models we will elucidate the pathomechanism underlying the disease of these patients.
Discovery Early Career Researcher Award - Grant ID: DE130101760
Funder
Australian Research Council
Funding Amount
$374,000.00
Summary
Uncovering the roles of key ribonucleases critical for post-transcriptional control of chloroplast gene expression. Higher plant chloroplasts harbour key biological processes that are essential to life on earth. Deciphering the roles of important plastid-targeted ribonucleases, central to post-transcriptional ribonucleic acid (RNA) processing events, is crucial to elucidate the genetic elements required to engineer chloroplast metabolic pathways to enhance productive crop yields.
This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
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.
Genomic Analysis Of DNA Binding And Gene Regulation By The Chromatin Remodelling Factor UBF
Funder
National Health and Medical Research Council
Funding Amount
$624,254.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is the major anabolic event of a growing cell and is frequently dysregulated during disease such as cancer. This grant will examine a protein termed UBF that we think plays an important role in orchestrating the cellular response to dysregulated ribosome biogenesis. By understanding how UBF functions we hope to uncover novel therapeutic approaches to treat diseases associated with ribosome stress .
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.
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.
Methylation Sensitive Genes And The Transition To Allergic Disease: A Twin Study
Funder
National Health and Medical Research Council
Funding Amount
$493,843.00
Summary
Australia has amongst the highest reported prevalence allergic conditions (including asthma) in the world. Despite this, little is known about how these conditions arise. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of a unique collection of identical twins where one of a pair is sensitive to house dust mite, with cutting edge genomics, to characterise the pathways leading to allergy in ....Australia has amongst the highest reported prevalence allergic conditions (including asthma) in the world. Despite this, little is known about how these conditions arise. Mounting evidence implicates environmentally induced disruption of the genetic blueprint via a process known as epigenetics. We are combining the strengths of a unique collection of identical twins where one of a pair is sensitive to house dust mite, with cutting edge genomics, to characterise the pathways leading to allergy in children.Read moreRead less
Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people w ....Platelets are key blood elements that are essential for the prevention of bleeding in response to injury or infection. Overactive or spontaneously active platelets cause thrombosis and blood clot formation. My laboratory has identified new physiological pathways of activation of platelet metalloproteinases, the enzymes that regulate surface levels of the prothrombotic platelet receptors. By understanding this mechanism of receptor regulation, we can uniquely target platelet receptors in people with prothrombotic pathologies.Read moreRead less