Molecular Targeting Of Innate Immune Signalling Pathways In Cancer And Auto-Inflammatory Diseases
Funder
National Health and Medical Research Council
Funding Amount
$753,300.00
Summary
To achieve an accurate molecular understanding of innate immune system receptor signalling, both intracellularly and in whole organisms, in health and disease. This knowledge will then be used to generate better treatments for the extensive range of human diseases that are caused or exacerbated by dysfunctional innate immune signalling, including Crohn's disease, psoriasis and cancer.
This application describes a research proposal that will achieve an accurate molecular understanding of innate immune system receptor signalling in health and disease. This knowledge will then be used to generate better treatments for the extensive range of human diseases that are caused or exacerbated by dysfunctional innate immune signalling, including Crohn's disease, psoriasis and 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 Role Of PLZF In Regulating The Antiviral Activity Of Interferons
Funder
National Health and Medical Research Council
Funding Amount
$652,005.00
Summary
Interferons are the first line of defence against viral infection. We have shown that the transcription factor promyelocytic leukemia zinc finger protein (PLZF) is a novel regulator of the interferon response. Thus we hypothesize that PLZF is a critical component of the host's innate immune system. This study will provide new insights into the understanding of signal transduction mechanisms, as well as improve our ability to modulate sensitivity to interferon to protect against viral diseases.
Understanding The Role Of The IL11-Stat3-Th17 Signaling Axis In Gastrointestinal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$531,743.00
Summary
Gastrointestinal cancers arise when abnormal cells grow out from otherwise normal tissue. The resulting tumours contain a number of different types of cells, some of which help the tumour to grow, and some of which fight the tumour. We are interested in understanding how soluble molecules called cytokines influence the cells that promote tumour growth. In particular, we will explore the role of a cytokine called Interleukin-11 in these processes to identify novel cancer therapies.
Interleukin-1β Biology: Mechanisms Of Regulation, Activation And Secretion
Funder
National Health and Medical Research Council
Funding Amount
$641,979.00
Summary
The protein called intelreukin-1 (IL-1) is required to fight off invading pathogens but more recently has been implicated as contributing to diverse diseases characterised by excessive inflammation, such as arthritis, gout, atherosclerosis and even cancer. This project aims to understand how IL-1 is made within cells and then activated to cause inflammation, which will enable these processes to be therapeutically targeted.
Mapping The TNF Pathway: A Qualitative And Quantative Molecular Analysis Of The Components And Post-translational Modifications Involved In Physiological And Pathological TNFR1 Signalling
Funder
National Health and Medical Research Council
Funding Amount
$636,258.00
Summary
TNF is a master regulator of the inflammation response and dysregulated TNF signalling causes many human diseases. We will use a cutting edge mass spectrometry technique that we have developed to analyse molecules required for TNF signalling. Understanding how the TNF signalling works in all cell types and with different forms of ligands will open up therapeutic opportunities to selectively target TNF signalling in inflammatory diseases, such as Rheumatoid Arthritis and Cancer.
ROLE OF RIP KINASES & IAPs IN MUCOSAL IMMUNE DEFENCE
Funder
National Health and Medical Research Council
Funding Amount
$631,168.00
Summary
Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes in ....Pathogenic bacteria are master manipulators of the inflammatory signalling pathways designed to thwart them. Understanding how they do this will allow us to develop drugs that limit their ability to infect. We have shown that pathogenic bacteria inject a protein called EspL into human cells to promote the destruction of a family of human proteins, called RIP Kinases (RIPK), that co-ordinate the inflammatory response and aim now to discover how EspL causes RIPK degradation and thereby promotes infection.Read moreRead less
Structure-function Of Type I Interferon Receptors: Informing The Basis For Selective Modulation Of Signal Transduction And Function
Funder
National Health and Medical Research Council
Funding Amount
$1,316,153.00
Summary
Interferons (IFNs) are a family of proteins with critical roles in infectious and inflammatory diseases and cancers. Currently we do not understand why there are so many type I IFNs, their different functions and how they are achieved. This project will determine at a fine molecular level how different IFNs interact with molecules on target cells and transmit particular signals. We will focus on a novel IFN? that we discovered. These studies will underpin the development of new therapies.