MICROFABRICATED DEVICES: A SIGNIFICANT ADVANCE FOR THE DETECTION AND MOLECULAR ANALYSES OF CIRCULATING CANCER CELLS?
Funder
National Health and Medical Research Council
Funding Amount
$422,107.00
Summary
Using advanced microfabrication concepts, this project aims to develop a platform technology able to capture tumour cells circulating in the blood of cancer patients. Although present only in extremely small numbers, these cells provide invaluable insights into the pathophysiology of the disease and consequently provide vital diagnostic and prognostic information. Molecular analyses of these cancer cells could ultimately enable the design of improved and personalized cancer treatment.
Determinants Of Circulating Surfactant Protein Levels In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$276,221.00
Summary
The lung allows the oxygenation of blood and clearance of carbon dioxide. To achieve this a large surface area (50-100 m2) interfaces with a complex microcirculation across a 0.1-0.2 ?m barrier - the alveolocapillary membrane. The alveolocapillary membrane is damaged under a variety of circumstances, of varying severity. Whereas severe impairment results in respiratory failure, often there is no clear delineation between OacceptableO and OpathologicalO changes. Therefore, we have coined the term ....The lung allows the oxygenation of blood and clearance of carbon dioxide. To achieve this a large surface area (50-100 m2) interfaces with a complex microcirculation across a 0.1-0.2 ?m barrier - the alveolocapillary membrane. The alveolocapillary membrane is damaged under a variety of circumstances, of varying severity. Whereas severe impairment results in respiratory failure, often there is no clear delineation between OacceptableO and OpathologicalO changes. Therefore, we have coined the term Olung healthO to encompass the broad spectrum. Generally speaking, lung health can be compromised by lifestyle or disease. Whereas lifestyle changes are typically progressive and chronic, those associated with disease tend to be severe and acute. Monitoring lung health clearly has important implications in terms of occupational health and lifestyle issues, including smoking. The need for a marker of lung permeability is also regarded as the Oholy grailO in the intensive care setting. Currently, there is no way of doing so. The alveolus is lined with a liquid layer into which is secreted a complex mixture of lipids and specific proteins known as alveolar surfactant. Surfactant reduces the work of breathing. Recently, we fortuitously discovered that surfactant proteins leak into the circulation and that changes in their levels are a sensitive and early generic index of the lung?s integrity. We discovered that lung damage from conditions as diverse as smoking to the acute respiratory distress syndrome elevate circulating surfactant proteins levels. To refine our discovery we aim to: Improve the techniques used to measure the proteins Study the rate at which they enter and clear the circulation Study the influence of storage, gender, age, circadian rhythm, and smoking on the levels Study the levels in acute lung injury and in radiotherapy and cytotoxic drug treatment where the ability to monitor lung damage has immediate benefit for the patients.Read moreRead less
The behaviour of prostate cancer cells is regulated by their surrounding environment known as the stroma. The stroma has been proposed as a therapeutic target, but it is a diverse mix of cells that needs to be specifically targeted. Not all stromal cells are equal; cells surrounding tumours have different features from cells in normal tissue. Therefore, the goal of this project is to directly isolate cancer-associated stromal cells from patient tissue and study their role in cancer progression.
Understanding The Molecular Pathways That Determine Response To Anti-angiogenic Therapy
Funder
National Health and Medical Research Council
Funding Amount
$209,539.00
Summary
Anti-angiogenesis is an important new approach to treat conditions such as cancer and eye disease. Our study is designed to understand the molecular pathways that lead to patients either being or developing resistance to these treatments. Using advanced cell and molecular biology techniques we will identify ways in which the blood vessels evade these therapies. Once identified these molecules will provide additional targets for developing therapeutics and diagnostics.
Adult and embryonic stem cells have enormous therapeutic potential. Haemopoietic stem cells have been the most intensely studied and widely used in a therapeutic setting, yet we have only a patchy knowledge of the genes required for their proliferation and survival. I will use classical genetic screens in the mouse to identify genes that regulate stem cell behaviour. I will analyse two existing mutant mouse strains with reduced numbers of haemopoietic stem cells, and execute a novel genetic scre ....Adult and embryonic stem cells have enormous therapeutic potential. Haemopoietic stem cells have been the most intensely studied and widely used in a therapeutic setting, yet we have only a patchy knowledge of the genes required for their proliferation and survival. I will use classical genetic screens in the mouse to identify genes that regulate stem cell behaviour. I will analyse two existing mutant mouse strains with reduced numbers of haemopoietic stem cells, and execute a novel genetic screen utilising mice with a defect in the self-renewal of adult haemopoietic and neural stem cells, to find mice with a recovered stem cell compartment.Read moreRead less
The Role Of CD4+ T Cells In The Tumour Killing By CD8+ Memory T Cells.
Funder
National Health and Medical Research Council
Funding Amount
$303,000.00
Summary
It has been observed that human cancers grow in spite of the presence of tumour antigen specific memory CD8+ tumour killer T cells in the body. These memory killer cells are unable to kill the cancer. Our research work in a mouse model indicates that the CD8+ T cells can be activated to kill cancers if cancer antigen specific CD4+ T helper cells are activated. The mechanism how this happens is not clear. The role of regulatory or suppressor CD4+ T cells are also not known. In this proposal we wi ....It has been observed that human cancers grow in spite of the presence of tumour antigen specific memory CD8+ tumour killer T cells in the body. These memory killer cells are unable to kill the cancer. Our research work in a mouse model indicates that the CD8+ T cells can be activated to kill cancers if cancer antigen specific CD4+ T helper cells are activated. The mechanism how this happens is not clear. The role of regulatory or suppressor CD4+ T cells are also not known. In this proposal we wish to study the mechanism of how CD8+ memory T cells get activated to cancer killer cells by the CD4+ T helper cells. This information will help us to design better immunotherapies for cancer patients.Read moreRead less