Suppression Of Immunity By The Malaria Parasite Antigen Plasmodium Falciparum Erythrocyte Membrane Protein-1 (PfEMP-1)
Funder
National Health and Medical Research Council
Funding Amount
$96,698.00
Summary
The malaria parasite P. falciparum infects red blood cells and makes the cells put on their surface a protein called PfEMP-1. The parasite can effectively “hide” by constantly changing this protein and making it unrecognizable by the immune system. PfEMP-1 can also suppress the immune system so that it can’t respond adequately to infection. Therefore, understanding PfEMP-1 function is important. I will investigate how PfEMP-1 can do this by looking at its cross talk with the immune system.
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.
New Insights Into Mechanisms That Coordinate Kinase Signalling And Molecular Motors In Mitosis: A Novel Role For The Protein Scaffold WD-repeat Protein 62 (WDR62).
Funder
National Health and Medical Research Council
Funding Amount
$529,122.00
Summary
Proteins perform all functions within a cell. Commonly, different proteins are assembled into large complexes to carry out processes, such as cell division, with significant implications for human health. Scaffold proteins facilitate the proper assembly of large complexes but are a poorly understood protein class. We will perform molecular analysis of a newly discovered scaffold, WDR62, to define how it drives cell division and reveal how this can be exploited to develop new anti-cancer drugs.
Why Is The Hijacking Of A Human Erythrocyte Signalling Pathway Essential For Malaria Infection?
Funder
National Health and Medical Research Council
Funding Amount
$510,890.00
Summary
Malaria drug resistance is spreading and the world needs cost-effective new drugs. We found 2 human enzymes, known targets of cancer chemotherapy, to be key for parasite survival in red blood cells. We aim to understand why these human proteins are crucial for the parasite and to identify new human proteins hijacked by malaria. This will open exciting options for antimalarial drug discovery: to harness funds invested in cancer drugs by targeting proteins with dual roles in cancer and malaria.
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.
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.
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.