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.
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.
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
Uncovering The Basis Of Inflammatory And Immunodeficiency Diseases
Funder
National Health and Medical Research Council
Funding Amount
$15,718,075.00
Summary
A world-class team from 3 institutions, spanning disciplines of clinical and experimental immunology, therapeutics, signalling and genetics, will identify how immune and inflammatory responses are controlled in both health and disease. The major outcomes of this work will be the generation of new knowledge, concepts and approaches to diagnose, prevent and treat the major human health problems of autoimmune diseases, inflammation, allergy and immunodeficiency.
The Shape of Plants; Discovering factors that control morphology by organizing the cytoskeleton. Understanding how plants generate the huge diversity of shapes seen in nature is both a scientific challenge and a biotechnological opportunity. Microtubules dominate cell architecture, providing dynamic, yet rigid, frameworks for defining or changing growth polarity. We recently discovered and cloned MOR1, a gene that is essential for organizing microtubules and controlling morphogenesis. This place ....The Shape of Plants; Discovering factors that control morphology by organizing the cytoskeleton. Understanding how plants generate the huge diversity of shapes seen in nature is both a scientific challenge and a biotechnological opportunity. Microtubules dominate cell architecture, providing dynamic, yet rigid, frameworks for defining or changing growth polarity. We recently discovered and cloned MOR1, a gene that is essential for organizing microtubules and controlling morphogenesis. This places us in a strong position to resolve a long-standing mystery: how are microtubules organized? We intend to define MOR1's structural attributes, identify its interacting proteins and innovate an ambitious screen for additional genes that have related functions. This project should stimulate new ideas and applications.Read moreRead less
Investigating The Cellular Response To Iron-Depletion: The Trilogy Of ASK1, Thioredoxin And Ribonucleotide Reductase
Funder
National Health and Medical Research Council
Funding Amount
$552,572.00
Summary
Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for t ....Iron is crucial for many essential biological processes. Recently, we demonstrated that iron-depletion can affects important signalling pathways (e.g., JNK and p38) that play important roles in growth arrest and apoptosis. This study is designed to investigate the cellular and molecular effects of iron depletion which currently remains unclear. The research is crucial for understanding: (1) the effects of iron deficiency and (2) for understanding the effects of iron chelators that are used for treating various diseases.Read moreRead less