Characterisation Of The Molecular Mechanisms Of Abeta-induced Proteolysis Of The Neural Cell Adhesion Molecule 2 (NCAM2)
Funder
National Health and Medical Research Council
Funding Amount
$374,666.00
Summary
Neurons in the brain are connected by synaptic contacts. Amyloid beta peptide accumulating in the brain in Alzheimer’s disease destroys synaptic contacts by degrading synaptic cell adhesion molecules which maintain the structure of the contacts. The aim of the project is to characterise the molecular mechanisms of amyloid beta-dependent degradation of synaptic cell adhesion molecules. The project will identify strategies that can be used to inhibit synapse loss in Alzheimer’s disease.
Exploring The Role Of Arrcd4 In Extracellular Vesicle Biogenesis And Its Implications In Tissue Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$678,742.00
Summary
Most cells in the body release small packages known as extracellular vesicles (or EVs in short), which carry proteins and other cellular material. EVs transport important cellular messages required for the everyday function of cells and play crucial roles both in normal wellbeing and disease. This proposal will investigate how EVs are formed, how they select their protein content and how they contribute to the maturation of some cell types in the body.
A Novel Mechanism For Regulating Membrane Proteins By Ubiquitin Ligases And Their Adaptors
Funder
National Health and Medical Research Council
Funding Amount
$627,897.00
Summary
Many membrane proteins act as ion channels, transporters or receptors for extracellular ligands and are critical to normal functioning of the cell. These proteins are generally regulated by transport to or from the membrane to ensure that correct levels are maintained at the membrane. This proposal is to study a novel way of regulating membrane proteins. The successful completion of the work will provide important knowledge relevant to many human diseases.
Molecular Basis Of Artemisinin Action And Resistance In Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$758,464.00
Summary
The malaria parasite, P. falciparum causes ~450,000 deaths each year. Resistance to the front-line antimalarial drug, artemisinin, is increasing, threatening at least another 100,000 lives per year, and potentially causing an additional ~A$500M in lost productivity. This project will identify the components of the parasite's cellular defence system that underpin resistance and will point to strategies for overcoming resistance to this important drug class.
Determining The Role Of Parkin And PACRG In Protein Turnover
Funder
National Health and Medical Research Council
Funding Amount
$555,780.00
Summary
Alterations in the parkin gene are associated with neurodegenerative disorders such as Parkinson's disease (PD). The aim of this proposal is to characterise the function of parkin and the role it plays in disease development. We will determine the role of parkin in the brain and how loss of this function causes specific nerve cells to die. These studies will provide the means to develop novel therapeutic approaches to alleviate or prevent these disorders.
Molecular Basis For The Efficient Processing Of Antigens Taken Up By Clec9A, A DAMP Receptor On Dendritic Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,302,392.00
Summary
Dendritic cells (DC) of the immune system utilise specific receptors to sense danger signals from their environment. We identified a DC danger receptor, Clec9A, which recognizes and induces immunity to “dangerous” dead cells eg. infected cells or killed tumour cells. We will investigate how DC use Clec9A to process “dangerous” dead cells, and the factors that control the potency of this immune response. This will enable us to develop novel immunotherapies for infectious diseases and cancer.
Enhancing Vaccine Efficacy By Harnessing Dendritic Cell Receptors And Their Unique Properties
Funder
National Health and Medical Research Council
Funding Amount
$687,519.00
Summary
Potent vaccination might be achieved by using monoclonal antibodies as magic bullets to target vaccines to special cells in the body. We show that targeting these special cells by using monoclonal antibodies that recognise Clec9A is effective, perhaps because it brings several different immune cells together so that they orchestrate very efficient immune responses. This application investigates how targeting Clec9A allows strong vaccination so that we can apply this to new generation vaccines.
Characterising An Important Control Point In Cholesterol Synthesis Beyond HMG-CoA Reductase
Funder
National Health and Medical Research Council
Funding Amount
$480,739.00
Summary
The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol- ....The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol-related diseases.Read moreRead less
The Regulatory Role Of Clec12A In Antigen Presentation And Inflammatory Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,381,077.00
Summary
The immune system maintains a balance between initiating immune responses to infections and suppressing immune responses in health. We have identified, on the surface of specialised immune cells, a protein that is critical for regulating immune responses and dampening down inflammation. This proposal aims to determine how this protein functions in health and under inflammatory conditions, and to develop approaches based on its molecular interactions to reduce inflammatory disease.
Molecular Characterisation Of The Dendritic Cell Receptor Clec9a And Its Ligand Interactions
Funder
National Health and Medical Research Council
Funding Amount
$651,784.00
Summary
The immune system senses danger from infectious diseases, damaged and dead cells. We identified a danger receptor, Clec9A, on a specialised cell type of the immune system in mice and humans. Clec9A recognizes and induces immunity to dangerous dead cells. Delivering vaccines to Clec9A improves vaccine responses. We will investigate how Clec9A recognises and reacts to danger, and how we can mimic this recognition to improve vaccine design.