Characterisation Of Two New Kinases In The Hippo Tumour Suppressor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$550,602.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the Gish and Fray kinases control tissue growth by regulating the Hippo pathway. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
Control Of Organ Size And Cancer By The Hippo Pathway
Funder
National Health and Medical Research Council
Funding Amount
$638,517.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the Hippo pathway controls tissue growth and cancer. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
Tao Kinase, A New Member Of The Hippo Tumour Suppressor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
The Hippo pathway is a key regulator of tissue growth. It was first discovered in vinegar flies and plays a similar role in mammals. We aim to define the mechanism by which the Tao kinase controls tissue growth by regulating the Hippo pathway. These studies will be performed in flies and mammalian cell culture. Our studies will shed light on how tissue growth is controlled, and have the potential to inform the way that we treat human cancers and tissue growth disorders.
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.
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.
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.
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.
Regulation Of NOD Signalling By IAPs And RIP Kinases
Funder
National Health and Medical Research Council
Funding Amount
$643,172.00
Summary
Alterations in NOD signalling have been implicated in various human inflammatory diseases, particularly in Crohn’s disease and asthma. In this project we will identify new molecules that regulate NOD signalling and test the effect of drugs that inhibit known components of these pathways to determine their utility in treating inflammatory diseases.
Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understandi ....Histone deacetylase functions in immune cells. This project aims to define how an enzyme (a histone deacetylase) enables innate immune cells (macrophages) to respond to specific danger signals, such as those activating Toll-like Receptors. To identify processes that provide specificity to signal transduction pathways, this project will characterise protein targets and biological functions of a specific class IIa histone deacetylase in macrophages. This project expects to result in an understanding of histone deacetylases and protein deacetylation in immune cell responses which can be harnessed to manipulate cell functions for basic science and biotechnology uses.Read moreRead less