Only recently has it emerged that our cells have a built-in backup mechanism that instructs cells to die in extreme cases, such as when viruses have hijacked a cell. A misfiring backup mechanism is thought to underlie a number of human diseases, including inflammatory disease. Our investigation will establish a starting point for the development of novel anti-inflammatory drugs.
Structural and functional analysis of the protein kinase R. We have shown that protein kinase R (PKR) plays a key role in regulating the body's response to virus infections, inflammation and cancer. This project will identify mechanisms that regulate the activity of PKR and provide information useful for the development of novel drugs.
Molecular mechanisms of cyclic Adenosine Monophosphate (AMP) induced apoptosis. Cyclic Adenosine Monophosphate (cAMP) is an important cellular chemical necessary for cell growth. However, de-regulated cAMP production in response to altered physiology can result in cellular death or apoptosis. This is attributed to the development of certain human diseases and this project aims to understand the molecular mechanism behind this process.
Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic un ....Programmed cell death signalling in innate immunity. This proposal aims to address the under-explored potential for programmed cell death to promote innate immune cell signalling, which is a critical and fundamental biological process. It aims to generate new knowledge in the areas of cell death and innate signalling using innovative interdisciplinary approaches and discover new molecules that impact innate inflammatory responses. The expected outcomes of this project are to enhance our basic understanding of cell death, and build interdisciplinary collaborations. This work should provide significant benefit to the economy and health of Australians, as it is expected to identify molecules that will be of interest to the pharmaceutical and biotechnology industries.Read moreRead less
A molecular investigation into the naïve T cell repertoire. This project aims to interrogate the relationship between T cell receptor (TCR) recognition modes and T cell recruitment and activation. CD8+ T cells are important for adaptive immunity. Their recognition, via TCR, of peptides bound to MHC class I antigen-presenting molecules (pMHCI), initiates a signalling cascade which activates T cells effector functions. All structural information on TCR recognition of pMHCI is based on TCRs prevale ....A molecular investigation into the naïve T cell repertoire. This project aims to interrogate the relationship between T cell receptor (TCR) recognition modes and T cell recruitment and activation. CD8+ T cells are important for adaptive immunity. Their recognition, via TCR, of peptides bound to MHC class I antigen-presenting molecules (pMHCI), initiates a signalling cascade which activates T cells effector functions. All structural information on TCR recognition of pMHCI is based on TCRs prevalent in immune responses, and all recognise pMHCI using a conserved orientation. This project aims to use this observation to study the relationship between TCR recognition modes and T cell recruitment and activation.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100117
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Allosteric fingerprinting of G protein-coupled receptor monomers and oligomers. Allosteric modulation describes interactions between distinct, but conformationally linked, binding sites. Research will develop enabling technology using the unique profile, or 'fingerprint', of allosteric modulation at interacting and non-interacting G protein-coupled receptors to probe for receptor complexes within healthy and diseased tissue.
Exceptions Prove the Rule: How Antigen Recognition Drives T cell Activation. CD8+ T cells are immune cells that are critical for the adaptive immune response, which is central to immune function in vertebrates. CD8+ T cells mediate their effector functions only after activation, which occurs via T cell receptor (TCR) recognition of foreign antigens. Here, unique reagents and sophisticated technologies will be used to define precisely how the nature of TCR-antigen recognition impacts on T cell ac ....Exceptions Prove the Rule: How Antigen Recognition Drives T cell Activation. CD8+ T cells are immune cells that are critical for the adaptive immune response, which is central to immune function in vertebrates. CD8+ T cells mediate their effector functions only after activation, which occurs via T cell receptor (TCR) recognition of foreign antigens. Here, unique reagents and sophisticated technologies will be used to define precisely how the nature of TCR-antigen recognition impacts on T cell activation and effector function. This work builds on an earlier identification of an entirely novel mode of TCR-antigen recognition, and its success will establish novel paradigms in T cell biology and represent a key advance in knowledge in the life sciences.Read moreRead less
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
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.
Spatial And Temporal Dimensions Of Mu-opioid Receptor Signalling: Implications For The Development Of Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$799,316.00
Summary
The use of morphine as an analgesic is still limited by undesirable side effects such as tolerance. Despite decades of research, the mechanisms behind the development of tolerance are poorly understood. The ? opioid receptor is a protein expressed at the surface of the cells that is the target of morphine. This project will investigate the signalling events triggered by opioids with unprecedented resolution and will aim to elucidate why morphine elicits more tolerance than other opioid drugs.