Mast Cells Determine Susceptibility To Induction Of Systemic Immunomodulation By UVB Radiation
Funder
National Health and Medical Research Council
Funding Amount
$194,993.00
Summary
The ultraviolet B component of sunlight causes an immunosuppression in humans such that UV-induced tumours develop. In a murine model, we have shown that dermal mast cells at the irradiated site are crucially important in the mechanisms by which UVB stimulates this immunosuppression. In this project we wish to study in more depth the mechanisms by which sunlight stimulates mast cells to produce molecules which in turn signal immunosuppressive events. We hypothesise that there is an intermediary ....The ultraviolet B component of sunlight causes an immunosuppression in humans such that UV-induced tumours develop. In a murine model, we have shown that dermal mast cells at the irradiated site are crucially important in the mechanisms by which UVB stimulates this immunosuppression. In this project we wish to study in more depth the mechanisms by which sunlight stimulates mast cells to produce molecules which in turn signal immunosuppressive events. We hypothesise that there is an intermediary by which sunlight stimulates mast cell activity; we hypothesise that cis-urocanic acid may be involved directly or indirectly in this process. There is considerable evidence that histamine may be the major product of mast cells involved in this process; however it is unknown whether its primary action is on keratinocytes (stimulating prostanoid production), antigen presenting cells or lymph node cells. This project will also investigate the relationship of studies with mice to UVB-induced systemic immunosuppression in humans. Non-sun-exposed skin from controls and patients with non-melanoma skin cancers will be examined and dermal mast cell prevalence evaluated; we hypothesise that people with high dermal mast cell numbers are more prone to immunosuppression and thus, the outgrowth of UV-induced non-melanoma skin cancers. We hypothesise that there may also be qualitative differences in the mast cells of UV-sensitive and UV-resistant individuals; variations may occur in the granule contents of neutral proteinases or cytokines. It is necessary that we better understand the basis of immune system modulation by UVB that allows non-melanoma skin cancer development as these patients have a 20-30% higher risk of death from other cancers.Read moreRead less
Determining Regulators Of ILC3 In Mucosal Barrier Function And Immune Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$705,209.00
Summary
Innate lymphoid cells (ILCs) are specialized cells that defend the body against invading microorganisms at the body’s surfaces, mediate pathogen clearance and tissue repair but may also drive inflammatory conditions such as allergic asthma and inflammatory bowel disease. We will investigate the molecular switches that regulate this novel cell type and potentially uncover novel molecules or pathways for therapeutic targets.
Characterisation Of Immune Regulators In The Human Myometrium.
Funder
National Health and Medical Research Council
Funding Amount
$85,285.00
Summary
Premature birth is a major cause of perinatal death and morbidity. It further predisposes the individual to increased morbidity throughout life. Although the mechanism of birth has been heavily researched with an objective of preventing preterm babies, it is still not fully understood. A major problem has been the lack of suitable and accessible animal models. A key organ coordinating the birth event is the uterine smooth muscle, myometrium. For effective birth and delivery, the myometrium needs ....Premature birth is a major cause of perinatal death and morbidity. It further predisposes the individual to increased morbidity throughout life. Although the mechanism of birth has been heavily researched with an objective of preventing preterm babies, it is still not fully understood. A major problem has been the lack of suitable and accessible animal models. A key organ coordinating the birth event is the uterine smooth muscle, myometrium. For effective birth and delivery, the myometrium needs to be contracting synchronously in a coordinated manner to dilate the cervix while pushing the fetus into position for eventual delivery through the birth canal. This project aims to characterise the molecular events occurring at the myometrium which precedes and precipitates labour. These local changes will be linked with the systemic hormonal changes in order to approach a model for human parturition.Read moreRead less
Colorectal cancer is a leading cause of cancer-related deaths worldwide. Chronic inflammation is recognized as a predisposing factor for the development of colon cancer, but the molecular mechanisms linking inflammation and tumourigenesis have remained elusive. Our work will dissect the cellular and molecular circuitry that leads to tumourigenesis and investigate interventions aimed to significantly slow or prevent tumour formation. This work will have significant implications for treatments of ....Colorectal cancer is a leading cause of cancer-related deaths worldwide. Chronic inflammation is recognized as a predisposing factor for the development of colon cancer, but the molecular mechanisms linking inflammation and tumourigenesis have remained elusive. Our work will dissect the cellular and molecular circuitry that leads to tumourigenesis and investigate interventions aimed to significantly slow or prevent tumour formation. This work will have significant implications for treatments of intestinal inflammation and colon cancer.Read moreRead less
Failure-to-progress In Human Labour Results From A Profound Electrical Negativity Of The Uterine Cells: Targeting The Ion Channels Involved
Funder
National Health and Medical Research Council
Funding Amount
$564,541.00
Summary
The incidence of failure to progress in labour has increased in recent years, being linked to the rise in obesity. The result is a significant escalation in the rate of delivery by Caesarean Section (CS) which increases the risk of serious complications during subsequent pregnancies. We have identified dysfunctional systems associated with poor uterine contraction. We now aim to determine the mechanisms underlying these dysfunctional systems to lay the foundations for better therapeutics.