Influence Of TNF And TGF-beta On Langerhans Cell Mobilisation From Regressor And Progressor Skin Tumours
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Skin cancer is the most common type of cancer in humans. It is caused by the ultraviolet wavelengths found in sunlight. Australia has the highest incidence of skin cancer in the world, due to the large amount of sun exposure experienced by Australians during work and leisure. Considerable research needs to be directed towards this disease to understand how it forms and how it can be treated. Skin cancer can be controlled by the immune system, which in some cases is able to destroy the cancer, so ....Skin cancer is the most common type of cancer in humans. It is caused by the ultraviolet wavelengths found in sunlight. Australia has the highest incidence of skin cancer in the world, due to the large amount of sun exposure experienced by Australians during work and leisure. Considerable research needs to be directed towards this disease to understand how it forms and how it can be treated. Skin cancer can be controlled by the immune system, which in some cases is able to destroy the cancer, so that it disappears, or regresses. Other skin tumours fail to be destroyed by the immune system and therefore grow progressively. Differences between progressor and regressor tumours can help define why the immune system is able to destroy some but not other tumours. The cell of the immune system that is responsible for initiating immune responses against skin cancer is called the Langerhans cell. This cell migrates between the cancer and the local lymph node, where it activates lymphocytes to leave the lymph node and destroy the cancer. Our studies have shown that a major difference between progressor and regressor skin tumours is the ability of Langerhans cells to migrate from these tumours. Skin tumours produce cytokines (hormone like molecules) which enhance or inhibit Langerhans cell mobilization from the tumour. We have identified some of the cytokines involved, and plan to study how these cytokines interfere with this process and whether they do this by increasing the production of other factors, or by having a direct influence on the Langerhans cells. This knowledge would increase our ability to utilize these cells for treatment of cancer. This study will also further basic understanding of the biological factors which regulate the movement of this important cell from our tissues to the draining lymph node, which is of fundamental importance in the development of immunity.Read moreRead less
Dissecting The Contribution Of CD103+ DC To Priming Of Virus-specific CD8 T Cells
Funder
National Health and Medical Research Council
Funding Amount
$336,767.00
Summary
Dendritic cells are key regulators of T cell responses against pathogens. This project will examine the contribution and individual function of distinct dendritic cell to the initiation of adaptive immune responses against herpes-simplex virus. Unraveling the delicate interplay between different dendritic cells will provide novel insights into host-pathogen interactions and will have important implications for the development of efficient vaccination strategies.
Defining The Mechanisms That Control Exocytosis And Cell Signalling In Health And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$473,477.00
Summary
This research focuses on pathways regulating nervous communication and hormone release. It centres on proteins that regulate this process and on the function of specific endocrine cells in health and disease. It uses unique research tools developed in this laboratory enabling the study of mechanisms regulating cell signalling. Through this research I aim to identify how the cells in our body communicate with each other and how this relates to diseases such as type 2 diabetes.
Do Synaptic-like Mechanisms Control Insulin Secretion?
Funder
National Health and Medical Research Council
Funding Amount
$593,235.00
Summary
An estimated 415 million people world-wide were diagnosed with diabetes in 2015. One of the causal factors in disease is the dysregulation of insulin secretion. We have developed new techniques to study insulin secretion that has led us to propose a new model for secretory control. This proposal sets out experiments to critically test this model. The outcomes could have wide-reaching impact on understanding and for future treatment and prevention of the diabetes.
The Structure And Function Of The Apical Domain In Insulin Secreting Beta Cells.
Funder
National Health and Medical Research Council
Funding Amount
$571,741.00
Summary
Loss of control of insulin secretion is causal in diabetes and therefore its understanding is a key goal to shed light on the disease. We have recently identified a new domain in the insulin secreting cells, called the apical domain. This proposal will define the role of this apical domain in controlling insulin secretion. The outcomes could provide new insights into how diabetes develops and new targets for therapies.
Cytoskeletal Regulation Of Adhesion Structure And Cell Movement
Funder
National Health and Medical Research Council
Funding Amount
$60,420.00
Summary
Metastatic (secondary) cancers are a frequent cause of patient mortality. Central to the development of metastasis is cell motility-movement. A key component of cell movement is the way that cells bind and release the extra-cellular matrix as they move. By understanding how the dynamics of cell interaction with the matrix are regulated, we will identify molecules that are critical to the development of metastatic cancer and thus novel targets for inhibition of metastasis.
The Preferential Release Of Young Insulin Secretory Granules.
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
The aim of this study is to investigate the cause of reduced glucose induced insulin secretion in type 2 diabetes. In pancreatic beta-cells, insulin is packaged and stored in secretory granules (SGs). Upon stimulation, these SGs deliver insulin to the bloodstream. It is known that insulin SGs exist in two functionally distinct pools; and one pool is preferentially secreted upon stimulation. How a cell can differentiate the two SG pools is unclear, and we will address this issue in this project.