MPM Non-invasive Imaging Of Biological Interactions Following Drug Delivery With Micro-nanoprojection Patches.
Funder
National Health and Medical Research Council
Funding Amount
$403,612.00
Summary
The overarching aim of my research is to develop and evaluate effective, practical and reproducible physical methods for delivering genes and drugs to specific immunologically-sensitive cells in the skin to ultimately treat and vaccinate against human diseases. I recently patented a method using arrays of nano-scale projections on a patch to accurately, efficiently and safely deliver biomolecules not just to specific skin cells, but also to organelles within them. Conceptually, the delivery devi ....The overarching aim of my research is to develop and evaluate effective, practical and reproducible physical methods for delivering genes and drugs to specific immunologically-sensitive cells in the skin to ultimately treat and vaccinate against human diseases. I recently patented a method using arrays of nano-scale projections on a patch to accurately, efficiently and safely deliver biomolecules not just to specific skin cells, but also to organelles within them. Conceptually, the delivery device is a set of microscopic nanoneedles coated with drug substance and applied to the skin as a small patch. The device is practical, needle-free and pain-free. The aim of this current project is to use the micro-nanoprojection array patches-configured to uniquely deliver biomolecules to cells within given strata-to find: 1) what delivery sites of antigen-expression plasmid- toll like receptor (TLR) agonist lead to strong humoral immune responses in the intact animal. 2) whether delivery of different TLR agonists have different effects on the maturation and migration of the different professional antigen presenting cells (APCs) in the skin, as visualised locally by Multi-Photon Microscopy (MPM). 3) whether differences in APC maturation and migration are associated with different systemic antibody responses. We will identify optimal delivery sites of drugs-vaccines to the skin (layer, cells targeted, duration of delivery) with MPM for desired systemic immune responses. This will have important contributions towards improving immunotherapeutics of major diseases via skin targeting with micro-nanoprojection array patch technologies (and other methods).Read moreRead less
CD4+CD8β+ Double-positive T-cell Regulation Of CD8 T-cell Responses
Funder
National Health and Medical Research Council
Funding Amount
$430,983.00
Summary
T-cells are a type of white blood cell that play an essential role in the immune system. CD4+CD8+ Double-Positive (DP) T-cells are a rare and poorly defined T-cell subset associated with skin disease - however their function and subsequently their contribution to disease is not known. Our preliminary data suggest that these DP cells may regulate the function of other immune populations in the skin. This project aims to deliver key insights into DP cells and their role in skin disease.
Dendritic Cell-mediated Induction Of T Cell Tolerance
Funder
National Health and Medical Research Council
Funding Amount
$654,725.00
Summary
Australia has some of the highest rates of immune-mediated diseases in the world. These diseases include autoimmune, allergic and inflammatory conditions. We will use a mouse model to study how dendritic cells can prevent the onset of these conditions by inactivating the immune cells that cause them. Our findings will aid in understanding why these diseases develop and how they may be prevented and treated.
Antigen Recognition By CD1a-restricted T Cells In The Human Immune System
Funder
National Health and Medical Research Council
Funding Amount
$615,520.00
Summary
Human immunity requires protective T cells that target foreign molecules for removal. Even though substantial populations of T cells exist that recognise lipid molecules, little is known about their basic biology. We will identify and characterise lipid reactive human T cells and examine their response to foreign or self-lipids expressed by infectious organisms and host cells. This work will have important implications in understanding lipid reactive T cells in health and disease.
We have identified a population of immune cells called ‘resident memory T cells’ that reside in tissues of the body. These resident memory T cells play an important role in controlling infections, but it is also apparent that they can lead to aberrant immune reactions, causing autoimmune diseases. This project aims to further our understanding of these immune cells, including how they can be identified and generated, and how they can be controlled to prevent disease.
Subset Determination Of Tissue-Resident T Cell Memory
Funder
National Health and Medical Research Council
Funding Amount
$473,394.00
Summary
Immunity relies on white blood cells called T cells that circulate around the body and which are also found permanently lodged at body surfaces. It is non-circulating T cells that are the most important in protecting against infection. In this application we propose to show that only a subset of T cells can form the resident population and to identify the molecules that determine T cell residency. This information can then be used for the efficient construction of disease preventing vaccines.
The body’s surfaces are continually under threat from microbes that may cause debilitating disease. Our ability to control such infections relies on our immune system, consisting of different cell types with specialised functions. We will study frontline immune cells that populate barrier tissues such as skin and mucosa where they provide enhanced local protection by responding vigorously on infection. Our studies will guide the development of future therapies harnessing our immune system.
Regulation Of Tissue-Resident Memory T Cell Development
Funder
National Health and Medical Research Council
Funding Amount
$494,554.00
Summary
A recently identified subset of T cells that reside in the skin are critical to combat viral infection. However, little is known about how these T cell populations are formed. This project will characterise the pathways required to generate these cells and will identify novel factors that regulate their development. A greater understanding of how these T cells can be generated will open the way to utilise these cells in new vaccine strategies.
Biological Function Of The Chemokine Receptor 6 Expression On B Cells
Funder
National Health and Medical Research Council
Funding Amount
$241,500.00
Summary
The correct movement of cells is important for the defence of the body against micro-organisms. White blood cells have to arrive quickly at the site of an infection and information about this infection has to be spread. White blood cells that navigate the body are using molecules on their surface termed as receptors which help them to detect the scent of their target. One of these receptors is located on white blood cells that produce antibodies and enables these cells to migrate to appropriate ....The correct movement of cells is important for the defence of the body against micro-organisms. White blood cells have to arrive quickly at the site of an infection and information about this infection has to be spread. White blood cells that navigate the body are using molecules on their surface termed as receptors which help them to detect the scent of their target. One of these receptors is located on white blood cells that produce antibodies and enables these cells to migrate to appropriate tissues . We want to know more about the biological role of this receptor and its functions during the immune response to pathogens. It would be of significant importance to understand the impact of these cell surface receptors in detail because this could open the possibility to new therapies of infectious diseases and chronic inflammation.Read moreRead less
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$15,780,848.00
Summary
This program focuses on understanding the development of immune response to viruses and other infectious agents using a broad array of techniques to dissect the function of various immune cell types and to explore the relationship between structure and function of important cell surface molecules. These studies will improve our ability to design new generation vaccines for combating infectious diseases, controlling cancer, or limiting autoimmune diseases like diabetes.