Tailoring Dendritic Cell Diversity To Advance Effective Immunotherapies
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Dendritic cells (DCs) constitute the first line of defense against infection and cancer. To achieve this feat, DC have evolved into a sophisticated network of specialized subtypes, although how this diversification process occurs is yet to be fully clarified. We have uncovered a new molecule, termed DC-SCRIPT, which has a key role in establishing the DC network, specialization and function. This offers crucial new clues as to how to manipulate DCs to either boost or dampen the immune system.
The Molecular And Cellular Trajectories Of Clonal Dendritic Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$826,742.00
Summary
Dendritic cells (DCs) are a blood cell type with a crucial role in our immune system. They are made in the bone marrow from stem and progenitor cells. How each of these cells individually makes DCs is complex and dynamic. We seek to understand this using cutting edge technologies to track each cell’s step-by-step role in this important process. This knowledge may help the use of DCs in the treatment of several diseases including autoimmunity and cancer.
Dendritic cells (DCs) are the body’s sentinels, with three specialized subtypes. They monitor for infections and cancer and then activate immune T cells to clear it. Interestingly, they can all arise from a single cell, but the precise steps are unknown. By literally filming this process and analyzing the movie, we hope to draw the ‘family trees’ that lead to their generation. This knowledge will offer crucial clues as to how to boost or reduce their numbers for medical applications.
Immune Modifying Particles - A Novel Therapeutic Strategy To Treat West Nile Virus Encephalitis
Funder
National Health and Medical Research Council
Funding Amount
$550,926.00
Summary
The outcome of viral infection of the brain is determined by the attraction of white blood cells, especially monocytes into the brain. Monocytes have a paradoxical role during brain inflammation. On one hand they are essential defenders against viral infection. On the other they may cause lethal brain damage. This project aims to define the mechanism(s) through which a novel therapeutic strategy, known as immune modifying particles, can modulate monocytes migration and function during brain infe ....The outcome of viral infection of the brain is determined by the attraction of white blood cells, especially monocytes into the brain. Monocytes have a paradoxical role during brain inflammation. On one hand they are essential defenders against viral infection. On the other they may cause lethal brain damage. This project aims to define the mechanism(s) through which a novel therapeutic strategy, known as immune modifying particles, can modulate monocytes migration and function during brain infection.Read moreRead less
Members Of The CMRF-35 Leukocyte Receptor Complex On Human Chromosome 17q22-24 Modulate Immune Function
Funder
National Health and Medical Research Council
Funding Amount
$489,750.00
Summary
We have identified and characterized a group of proteins on the surface of different white blood cells called the CMRF-35 molecules. We hypothesize that these molecules play a role in regulating an immune response by acting as thermostat molecules i.e. molecules able to trigger or inhibit the immune response. This project aims to define the role of two of these molecules in regulating white blood cells in their response to foreign molecules or antigens. This project will have significant impact ....We have identified and characterized a group of proteins on the surface of different white blood cells called the CMRF-35 molecules. We hypothesize that these molecules play a role in regulating an immune response by acting as thermostat molecules i.e. molecules able to trigger or inhibit the immune response. This project aims to define the role of two of these molecules in regulating white blood cells in their response to foreign molecules or antigens. This project will have significant impact on understanding whether these triggering and inhibitory signals initiated from the CMRF-35 molecules effects i) how the cells divide, ii) what molecules are secreted by the cells, iii) whether the cells can mature or iv) whether a cell survives or dies. Some of the molecules involved in sending these signals will be identified. The ability to trigger or inhibit cellular effects through these molecules may be important in some forms of myeloid leukemia and in the ability to help manipulate the immune response to fight tumors.Read moreRead less
Transcriptional Regulation Of Specialized Subsets Of Dendritic Cells In Control Of Infection
Funder
National Health and Medical Research Council
Funding Amount
$616,912.00
Summary
Immune protection against viruses and bacteria depends on specialized cells called dendritic cells that display components of the invading organisms on their surface. There are multiple different types of dendritic cell and each population plays a specialized role in defending the body against infection. Our work will provide the framework for directly targeting these cells for novel vaccines to re-program the immune system for clinical conditions such as cancer, allergy and autoimmunity.
The Developmental Hierarchy Of Haemopoietic Lineage Relationships
Funder
National Health and Medical Research Council
Funding Amount
$192,000.00
Summary
The blood cells are all the progeny of a very rare stem cell, that is thought to reside in the bone marrow. The stem cell maintains itself throughout the life span of the individual as well as generating the billions of more mature cell types required in the blood. However the processes and stages that immature cells pass through from the stem cell to ultimately a mature functional blood cell such as a lymphocyte remain disputed. This study aims to determine to relationship of the various blood ....The blood cells are all the progeny of a very rare stem cell, that is thought to reside in the bone marrow. The stem cell maintains itself throughout the life span of the individual as well as generating the billions of more mature cell types required in the blood. However the processes and stages that immature cells pass through from the stem cell to ultimately a mature functional blood cell such as a lymphocyte remain disputed. This study aims to determine to relationship of the various blood cell progeny with each other and thus to provide a lineage map of the system. To do this we will isolate precursors at various stages along the developmental pathways and determine their capabilities to produce the normal range of progeny. We will then use a number of genetically altered mouse strains to assess the genes involved in this process. These studies will help provide an underlying scientific basis to the attempts to development a number of stem cell therapies that are aimed at boosting or directing stem cell production in procedures such as bone marrow transplantation for leukemia and immune deficiency. In addition a number of characterized human blood malignancies seem to have developed along aberrant pathways indicating that inappropriate lineage specification may be a factor in cancer.Read moreRead less