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.
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.
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.
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.
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
T cells play a central role in the immune response. The primary event in T cell activation is the triggering of a specific T cell receptor (TCR). Our studies will define new mechanisms for the regulation of TCR-mediated T cell responses. Our studies may yield novel insight into processes that contribute to the development of type 1 diabetes & inflammatory bowel disease.
Regulation of mRNA translation by the microtubule-associated protein Tau. This project aims to understand the molecular processes in a cell type and subcellular compartment that underlies learning and memory formation. Fundamental neuronal functions such as synaptic strengthening and memory formation are dependent on the tightly regulated process of protein translation. The kinase Fyn (which is localised to dendritic spines where memories are formed) activates the ERK/S6 pathway leading to massi ....Regulation of mRNA translation by the microtubule-associated protein Tau. This project aims to understand the molecular processes in a cell type and subcellular compartment that underlies learning and memory formation. Fundamental neuronal functions such as synaptic strengthening and memory formation are dependent on the tightly regulated process of protein translation. The kinase Fyn (which is localised to dendritic spines where memories are formed) activates the ERK/S6 pathway leading to massive translation of the scaffolding protein Tau. More importantly, the activation of this cascade is Tau-dependent. This project aims to determine how Tau activates this pathway, and to decipher the physiological role of the Tau/Fyn/Tau feedback loop. This will inform our understanding of the molecular regulation of learning and memory.Read moreRead less
Toll-like receptors in infectious and inflammatory diseases: the double-edged sword of innate immunity. The innate immune system is the first line of defence against invading microorganisms. This project will explore the role of specific innate immune genes in the control of infections and the development of inflammatory diseases.
Huntingtin-associated protein 1 controls cell communication. The purpose of this study is to identify the mechanisms by which a novel regulator of cell communication which we have identified is able to control the release of chemical signals from a cell. This project will provide critical insight into a cellular pathway that underlies hormone secretion, neurotransmission and higher brain functions.
Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels ....Inflammasomes: molecular drivers of anti-microbial defence. The innate immune system is the body’s first line of defence against infection, but also drives unhealthy inflammation. Families of innate immune receptors, such as nucleotide-binding oligomerisation domain (NOD-like Receptors), were recently discovered to control both anti-microbial defence and unhealthy inflammation. This project will characterise the basic biology of NOD-like Receptors at the molecular, cellular and organismal levels, and will thereby lead to a greater understanding of the fundamental biological pathways controlling inflammation and defence against infection. This may ultimately lead to commercial opportunities for treating infection and chronic inflammation.Read moreRead less