The Molecular Basis By Which The Interleukin-6 Cytokine Promotes Emphysema
Funder
National Health and Medical Research Council
Funding Amount
$659,457.00
Summary
Interleukin 6 (IL-6) is a potent immuno-modulatory cytokine that is commonly elevated in emphysema, the 5th leading cause of death in Australia. To understand the role of IL-6 in emphysema, we aim to demonstrate here by using a unique mouse model for IL-6-driven emphysema and clinical biopsies from emphysema patients, that IL-6 uses an alternative signalling mechanism in emphysema termed trans-signalling. Therefore this project could provide novel therapeutic targets for emphysema.
A Novel Class Of Negative Regulators Of Interleukin-6 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$626,950.00
Summary
Cytokines are protein messengers that activate the immune system to fight infections. When they are too active they cause inflammation and autoimmune diseases so their activity needs to be tightly controlled. We have discovered a new family of regulators (the MARCH proteins) that inhibit cytokine activity by routing cytokine receptors for destruction. We aim to understand how this process works in detail and the role of MARCH proteins in vivo in ameliorating autoimmune diseases.
Characterisation Of Autophagy Deficiency In Skeletal Muscle Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$956,237.00
Summary
Defects in skeletal muscle are a cause of muscle disease, and also have broad health implications for diabetes, obesity and liver disease. As such, it is important to understand the processes required for healthy muscle and how signals communicate from muscle to the liver and fat, which integrate whole body metabolism. This application examines how the cellular degradation process known as autophagy integrates these important processes by investigating a novel gene regulator of this pathway.
We have identified a novel gene, Inpp5e, that when mutated causes a disease similar to Joubert syndrome and MORMS disease which leads to abnormal movements, developmental delays, mental retardation, abnormal breathing and eye movement. We have identified a candidate gene for these diseases and have shown that deletion of this gene in mice results in similar pathology. We aim to determine the mechanism by which Inpp5e regulates human development and disease.
Investigation Of The Role Of PI3-kinase In The Regulation Of Angiogenesis
Funder
National Health and Medical Research Council
Funding Amount
$837,660.00
Summary
The formation of blood vessels is critical for the development of embryos, but also after birth in processes such as wound healing. However, the uncontrolled formation of new blood vessels is also a feature of many human diseases such as cancer, and eye diseases that lead to blindness in adults or in premature infants. We propose to identify new regulators of blood vessel development, in order to improve current treatment therapies for these debilitating diseases.
Protein tyrosine phosphatases (PTPs) control cell communication networks referred to as cellular signaling. This proposal is focused on understanding the roles of PTPs in cellular signaling networks perturbed in human disease & delineating novel opportunities for therapeutic intervention
Understanding The Role Of The Atypical Cadherin Fat4 In Lymphatic Vascular Development
Funder
National Health and Medical Research Council
Funding Amount
$1,006,248.00
Summary
This application will define the role of a large cell adhesion molecule, FAT4, in lymphatic vascular development. By understanding how FAT4 functions in lymphatic vessels, we will gain insight to the mechanisms by which mutations in the gene that encodes this protein cause a human lymphoedema syndrome.
T cells play a central role in the immune response. The primary event in T cell activation is the triggering of a specific T cell receptor (TCR). Our studies will define new mechanisms for the regulation of TCR-mediated T cell responses. Our studies may yield novel insight into processes that contribute to the development of type 1 diabetes & inflammatory bowel disease.
Discovery Early Career Researcher Award - Grant ID: DE220100259
Funder
Australian Research Council
Funding Amount
$467,964.00
Summary
Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. T ....Interrogating the adaptive potential of skeletal muscle. Disruptions to muscle oxidative capacity and growth signalling underpin atrophy and dysfunction with ageing, which impacts on an individual’s quality of life. These biological processes are thought to be mutually exclusive and compete during muscle adaptation. This project aims to define how these processes regulate the extent of muscle adaptation, and how modifying these attributes influence functional capacity in the context of ageing. This project will provide fundamental new knowledge in understanding how modifying muscle attributes influence successful ageing. This knowledge will improve resilience, productivity, and wellbeing of all Australians, with implications for reducing societal and economic burden.Read moreRead less
Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. T ....Target Of Rapamycin control of nutrient uptake. This project aims to study nutrient uptake in eukaryotes. It is expected to generate new knowledge of critical and conserved features of environmental and Target Of Rapamycin (TOR)-mediated control of nutrient uptake, specifically endocytosis, building on novel preliminary data that identifies novel TOR control points. The expected outcomes include new insights into mechanisms controlling nutrient uptake and fostering institutional collaboration. This knowledge is highly relevant to any industry or research project utilising living organisms, as nutrient availability supports survival, cell growth and proliferation.Read moreRead less