Studies Of Cullin 5 Deficiency For Novel Insights Into SOCS Redundancy And Specificity
Funder
National Health and Medical Research Council
Funding Amount
$658,571.00
Summary
Cytokines are hormones that regulate blood cell production and function. The research proposed in this application focuses on the biological roles and biochemical mechanisms of action of an important family of proteins that control the actions of cytokines, thereby allowing their beneficial effects in coordinating oxygen transport, blood clotting and responses to infection, while preventing the harmful effects of excess responses, such as myeloproliferative diseases or autoimmunity.
Molecular Dissection Of Aberrant IL6/gp130 And TGF? Signaling In The Pathogenesis Of Interstitial Pneumonitis
Funder
National Health and Medical Research Council
Funding Amount
$590,009.00
Summary
Interstitial pneumonia (IP) is frequently observed in the group of lung diseases which affect the transfer of oxygen from inhaled air into the bloodstream. Current treatments for these diseases only effectively manage patient’s symptoms but don’t cure patients of IP. We have developed a strategy to identify the exact cell type responsible for an acute IP and the molecular intermediates that may offer novel treatments and pave the way for a possible cure for this disease.
Cancer causes significant morbidity and mortality in Australia’s aging population. There is strong evidence that abnormal blood vessels in tumours limit drug access and drive metastases. We have identified a molecule which controls vessel remodelling in tumours. In this proposal we will study mechanisms on how the molecule itself is regulated with the aim to normalize blood vessels for improved therapy.
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.
Targeting The Interface Between Tumours And Their Microenvironment For The Treatment Of Gastrointestinal Cancers
Funder
National Health and Medical Research Council
Funding Amount
$785,045.00
Summary
This fellowship explores the synergistic interactions between intestinal cancer cells and the tumour microenvironment and which promote survival, expansion, migration and invasion as well as facilitating the development of resistance to anti-cancer therapy. Aided by the clinical expertise of my collaborators, my efforts are likely to yield translational outcomes, including the development of therapeutic IL-11 antagonists, and of a serum protein signature indicative of early stage gastric cancer.
Role Of PTEN Catalytic Function In Suppression Of Cancer And Metastasis
Funder
National Health and Medical Research Council
Funding Amount
$758,319.00
Summary
PTEN mutations are frequently described in various types of cancer. This proposal outlines different experimental strategies to probe how modulation of distinct PTEN functions can affect signalling pathways and be responsible for oncogenic outcomes. We will use animal models and cell lines in culture to identify new signatures/biomarkers to stratifying patients on genetic and molecular bases, and to facilitate the design of tailored combinational therapies directed toward cancer eradication.
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.
The ZIC3 Heterotaxy-associated Transcription Factor: A New Player In Nuclear Control Of Canonical Wnt Signalling
Funder
National Health and Medical Research Council
Funding Amount
$992,822.00
Summary
Humans have many internal asymmetries that need to occur in a consistent manner across all individuals. Examples of asymmetry include our unpaired organs (like the heart or liver) or a paired organ with asymmetry (like the lungs). In this project we will use cutting edge molecular embryology and cell biology techniques to explore the mechanisms behind the remarkable feat of establishing asymmetry so we are better able to help those individuals with laterality disorders.
Novel Regulation Of Inflammasomes By Cytokine Signalling Pathways In Gastric Disease
Funder
National Health and Medical Research Council
Funding Amount
$674,772.00
Summary
Stomach inflammation (gastritis) is strongly associated with Helicobacter pylori bacterial infection, and can also progress to gastric cancer. However, it remains largely unknown how Helicobacter triggers these gastric diseases in people. Using a mouse model which develops gastric inflammation and tumours, our aim is to determine the role of protein complexes in the stomach called inflammasomes in triggering chronic inflammatory responses to Helicobacter that lead to gastric disease.
Regulator Of G Protein Signalling-5 Loss And Gain Of Function In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$625,428.00
Summary
Cancer and cardiovascular diseases are amongst the largest causes of morbidity and mortality in Western populations. We have identified a molecule, called Regulator of G protein signalling 5 (RGS5), which is involved in vessel remodelling in both diseases. This molecule is a prime candidate for drug development. We will study the precise role of RGS5 in sophisticated preclinical models which will create future opportunities for urgent therapy.