Cytokine-driven Allergic Inflammation: Characterization Of Two Isoform-specific Modes Of IL-3 Receptor Activation And Investigation Of New Receptor-associated Signalling Partners.
Funder
National Health and Medical Research Council
Funding Amount
$620,716.00
Summary
In asthma, the symptoms are caused by an allergic reaction in the lung orchestrated by immune cells which produce small proteins called cytokines thus stimulating inflammatory cell production. The cytokine IL-3 is critical for the production of basophils which have an important role in the inflammation. The project will investigate the molecular details of how the IL-3 binds to its receptor and stimulates basophil production and reveal new targets for controlling inflammation in asthma.
Immunodominance And Protective Immunity In The Context Of A Complex Host-pathogen System.
Funder
National Health and Medical Research Council
Funding Amount
$899,832.00
Summary
In experimental infection models with simple organisms, pathogen-specific immune responses recognize only a small fraction of potential epitopes encoded by the genome. This phenomenon is termed immunodominance. We propose the first comprehensive study of immunodominance in humans in response to a complex pathogen, the Plasmodium parasite that causes malaria. This will provide valuable new knowledge of host-pathogen immunity and facilitate rational vaccine design.
Characterization Of A Novel IFNbeta Signaling Axis Mediated Via IFNAR1
Funder
National Health and Medical Research Council
Funding Amount
$353,754.00
Summary
Type I interferons (IFNs) play an important role in regulating immune responses to pathogens and tumors and are used therapeutically. This project will investigate a novel IFN signaling axis that we have recently characterized that is mediated via the low affinity IFN receptor, IFNAR1. This signaling axis occurs independently of the high affinity IFN receptor IFNAR2 and contributes to lethality in a model of septic shock.
Characterisation Of The Adiponectin Receptors - AdipoR1 And AdipoR2
Funder
National Health and Medical Research Council
Funding Amount
$445,158.00
Summary
The increasing incidence of cardiometabolic disease highlights an unmet need for novel therapeutic approaches. Greater understanding of the detail governing cardiometabolic function is required to provide a foundation to construct effective strategies. We will characterise 2 novel receptors that are important in the regulation and maintenance of cardiometabolic systems, seeking to identify strategies to enhance receptor, improve cardiometabolic function and reduce disease burden.
Allosteric Targeting Of The Dopamine D2 Receptor: A Novel Approach For The Treatment Of Parkinson’s Disease And Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$469,644.00
Summary
The dopamine D2 receptor is a brain protein that is the target for drugs that are used in the treatment of schizophrenia and Parkinson's disease (PD). In both cases the current drugs have significant side effects because they simply act to switch the receptor off or on respectively. We will focus on a new class of drugs that, because they act to tune up or tune down the activity of the D2 receptor, may be a safer more effective approach to treat these disorders.
The Novel CXCR4/CCR7 Heterodimeric Chemokine Receptor Is A Key Determinant Of Breast Cancer Metastasis.
Funder
National Health and Medical Research Council
Funding Amount
$461,252.00
Summary
Novel cellular receptor has been identified that works as a switch to turn on cellular functions that are responsible for the metastatic dissemination of cancer cell to distant organs. The make-up and regulatory mechanisms of this novel receptor will be studied together with its potential utility as the marker of metastatic breast cancer.
The Structure And Composition Of The T-cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$434,644.00
Summary
Our research will provide a fundamental advance in our understanding of how foreign viruses and pathogens trigger the immune system. Gaining a greater understanding of these central events will facilitate the design of novel therapies to treat immune associated disorders such as transplant rejection, autoimmune disease and some cancers.
New Mediators Of GPCR-growth Factor Receptor Transactivation
Funder
National Health and Medical Research Council
Funding Amount
$607,842.00
Summary
Hormones bind to receptors on the surface of cells. Receptors can modify each other’s function and this “cross-talk” is important for the receptors for a peptide hormone (termed angiotensin) and a growth factor receptor (EGFR), which are major regulators of the cardiovascular system. We have identified a number of mediators of the angiotensin-EGFR crosstalk and this current grant aims to use molecular and cellular and in vivo approaches to examine the molecular basis of their actions.
Discovery And Mechanisms Of Host Cell Factors In HIV Uncoating
Funder
National Health and Medical Research Council
Funding Amount
$635,098.00
Summary
HIV entry into the host cell involves release of its capsid, a protein shell protecting the viral genome. The capsid hijacks host proteins to cloak itself from cellular defenses while the cell has evolved sensors that can block viral infection. This proposal aims to discover proteins involved in this arms race between host and virus and decipher how they control capsid disassembly. This insight will help design new drugs against HIV infection and new ways to deliver genes for gene therapies.
Mechanism Of Epidermal Growth Factor Receptor Transactivation
Funder
National Health and Medical Research Council
Funding Amount
$578,268.00
Summary
This application examines the cellular events that control heart growth in response to angiotensin, a hormone linked to heart failure. We believe that the same cell processes are also involved in cancer cell growth and by understanding the mechanism by which angiotensin promotes growth, better therapies against human cardiovascular disease and its relationship to uncontrolled growth will evolve.