Var Gene Diversity And Naturally Acquired Immunity To Malaria
Funder
National Health and Medical Research Council
Funding Amount
$410,664.00
Summary
In areas where malaria is common, people develop natural immunity to the disease albeit very slowly due to the many parasite strains that circulate. The project will use protein microarrays to investigate the patterns by which antibodies are acquired to the majority of strains. This will reveal how antibodies are acquired with age and which are associated with protection against malaria symptoms. The research aims to identify biomarkers of malaria immunity and may lead to new vaccine candidates.
Haematopoietic Stem Cell Glycome Regulates Outcome Of Niche Interactions
Funder
National Health and Medical Research Council
Funding Amount
$913,729.00
Summary
Hematopoietic stem cells (HSC) reside in the bone marrow (BM) and make all the cells of the blood system. We have found a factor in the BM which when blocked, puts normal HSC to sleep helping them survive chemotherapy. This means cancer patients should suffer less side-effects from their therapy. This factor also helps leukaemia stem cells (LSC) resist chemotherapy. Inhibitors may a) reduce patient mortality caused by chemotherapy and b) sensitise LSC to chemotherapy enabling long-term cure.
Mechanisms By Which Endothelial Selectins Regulate Normal And Malignant Stem Cell Fate
Funder
National Health and Medical Research Council
Funding Amount
$708,742.00
Summary
Hematopoietic stem and progenitor cells (HSPC) reside in the bone marrow (BM) and make all the cells of the blood system. We have found a molecule in the BM which when increased during inflammation, awakens normal HSPC. We previously showed this molecule also helps leukaemia and other cancer stem cells resist chemotherapy. We have now identified the mechanism why. These proposed studies open new therapeutic avenues to sensitise cancer stem cells to therapy enabling long-term cure.
Elucidating The Role Of Claudin-2 In Tumour Initiation And Metastasis Development From Colorectal Cancer: Consequence For Tumour Relapse
Funder
National Health and Medical Research Council
Funding Amount
$398,993.00
Summary
Mortality from colorectal cancer is often due to the development of metastases. Cancer stem cells (CSC) are suspected to provide a major drive for metastasis development, to resist current therapies, and to initiate tumour relapse. Yet, little is known about mechanisms that control CSC behaviour. Our project investigates the role of claudin-2, a cell adhesion protein that is strongly overexpressed in colorectal cancer, in the regulation of CSCs, metastasis development and tumour relapse.
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.
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.
The Impact Of The Changes In Levels Of Adhesion Molecules NCAM2 And DsCAM On Synapse Formation And Function: Implications For Down Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$334,053.00
Summary
Down syndrome (DS) results from triplication of chromosome 21 and leads to mental retardation, molecular mechanisms of which are not understood. We found that two proteins, NCAM2 and DSCAM, encoded at chromosome 21 are highly expressed in synapses. Synapses are specialized contacts between neurons which allow neurons to process information in the brain. In this project we will test a hypothesis that changes in NCAM2 and DSCAM expression result in synapse abnormalities observed in DS.
Transplantation of pancreatic islets is the only cure for type 1 diabetes (T1D). Unfortunately, many of the transplanted islet cells die quickly due to an inadequate supply of blood. Herein, we investigate a novel cell surface protein for its role in islet and blood vessel survival and function. Furthermore, we use nanotechnology to provide said protein to the islet cells during transplantation for increased survival and function. Ultimately, this work may cure more patients with diabetes.