The Interaction Of LPS Pathway Genes With Pre-natal And Early Exposure To LPS And Allergens Predicts Atopy At Age One
Funder
National Health and Medical Research Council
Funding Amount
$381,263.00
Summary
The poor understanding of the cause of asthma has made prevention strategies unsuccessful. This study will provide valuable data for understanding the interactions between exposure to environmental stimuli and LPS pathway genes on the development of allergy and asthma in infants. As environmental modifications and dietary interventions during pregnancy are being investigated, the findings from the proposed study will be important in guiding prevention practices of allergic diseases.
Alcoholic Chronic Pancreatitis: Induction, Progression And Reversal
Funder
National Health and Medical Research Council
Funding Amount
$632,211.00
Summary
Pancreatitis (inflammation of the pancreas) is a serious complication of alcohol abuse. Patients suffer from severe and often intractable abdominal pain, maldigestion and diabetes, We have recently shown that gut toxins (endotoxins) may act as a trigger factor for pancreatitis in alcoholics. The proposed project aims to characterise the effects of gut toxins on the pancreas during alcohol abuse so as to identify pathways that may be therapeutically targeted to prevent or retard the disease.
Alcoholic Pancreatitis : Role Of Alcohol, Endotoxin And Stellate Cells
Funder
National Health and Medical Research Council
Funding Amount
$501,653.00
Summary
The pancreas is the major digestive organ of the body. It contains many proteins (enzymes) which break down food. One of the more serious complications of alcohol (ethanol) abuse is pancreatitis, a condition that has both acute and chronic manifestations. Patients with acute pancreatitis suffer from acute abdominal pain; in severe cases the condition can be fatal. Repeated attacks of acute pancreatitis can lead to chronic pancreatitis, a condition in which, normal pancreatic tissue is lost and i ....The pancreas is the major digestive organ of the body. It contains many proteins (enzymes) which break down food. One of the more serious complications of alcohol (ethanol) abuse is pancreatitis, a condition that has both acute and chronic manifestations. Patients with acute pancreatitis suffer from acute abdominal pain; in severe cases the condition can be fatal. Repeated attacks of acute pancreatitis can lead to chronic pancreatitis, a condition in which, normal pancreatic tissue is lost and is replaced by scarring. This disease causes chronic pain, inability to digest food with consequent malnutrition and destruction of the insulin producing cells of the gland leading to diabetes. The mechanisms by which alcohol causes pancreatitis are not yet known. Although it is well established that the risk of developing pancreatitis increases with increasing intake of alcohol, suggesting that alcohol exerts toxic effects on the gland, it is also clear that not all alcoholics develop pancreatitis, indicating that an additional trigger factor-susceptibility factor is required to produce overt disease. The proposed project aims to determine the mechanisms responsible for alcohol-induced acute and chronic pancreatitis. It seeks i) to determine whether toxins from gut bacteria (endotoxins) may act as the trigger factor for acute alcoholic pancreatitis; and ii) to characterise the effects of alcohol and endotoxin on the cells responsible for pancreatic scarring, namely, pancreatic stellate cells. Our experiments will involve an animal model of alcohol feeding as well as pancreatic cells grown in dishes (cultured cells). Identification of the pathways by which alcohol causes pancreatic injury may enable the development of treatment strategies to prevent and-or retard the progress of alcoholic pancreatitisRead moreRead less
A Population-based Birth Cohort Study Of The Development Of Atherosclerosis In Early Life
Funder
National Health and Medical Research Council
Funding Amount
$780,067.00
Summary
Cardiovascular disease (heart attack and stroke) are leading causes of death and illness in adults in Australia. The changes in blood vessels that lead to these conditions begin before birth. This project investigates the factors that contribute to these early changes from birth onwards, and will facilitate development of targeted prevention in high-risk groups to reduce cardiovascular disease in later life.
The Role Of Mal In Toll-like Receptor Signal Transduction Of The Pro-inflammatory Response.
Funder
National Health and Medical Research Council
Funding Amount
$472,500.00
Summary
Sepsis kills more people per year than the cancers of the breast, colon, prostate and pancreas combined. Sepsis occurs in 1 of 50 hospital admissions and is the leading cause of death n intensive care units. The instance of sepsis has doubled in the last decade and is expected to increase. One of the major causes of sepsis si lipopolysaccharide (LPS), the main constituent of gram-negative bacteria's cell wall, and the prototypic inducer of the pro-inflammatory response of the innate immune syste ....Sepsis kills more people per year than the cancers of the breast, colon, prostate and pancreas combined. Sepsis occurs in 1 of 50 hospital admissions and is the leading cause of death n intensive care units. The instance of sepsis has doubled in the last decade and is expected to increase. One of the major causes of sepsis si lipopolysaccharide (LPS), the main constituent of gram-negative bacteria's cell wall, and the prototypic inducer of the pro-inflammatory response of the innate immune system. Dysregulation of the pro-inflammatory response can lead to sepsis. Recently, the mammalian receptor for LPS was found to be Toll-like receptor (TLR)-4, the activation of which activates a signal transduction pathway that initiates the pro-inflammatory response. We have previously shown a key role for an adapter protein called Mal in mediating signal transduction pathways upon activation of TLR-4. Interaction of Mal with a key signal transduction mediator called TRAF6 has been shown to induce the activation of the pro-inflammatory response. Furthermore, Mal has been found to undergo degradation which may indicate a means of regulating the continued activation of the pro-inflammatory pathway. This research program will investigate the role of Mal in mediating signal transduction in TLR activated macrophages, key responsive cells of the innate immune system to microbial infection. A greater understanding of these processes will assist in the development of therapeutics to alleviate the consequences of microbial-induced inflammation, including chronic inflammatory diseases and sepsis.Read moreRead less