Defining the molecular and cellular mechanisms of beta cell dysfunction. This project will investigate the influence of environment in the functional adaptation and maladaptation of pancreatic beta cells in diabetes. The research will define the molecular and cellular mechanisms linking environmental triggers such as obesity, high fatty acid levels and hyperglycaemia to beta cell dedifferentiation and dysfunction.
Endocrine And Molecular Regulation Of Placental CRH Expression
Funder
National Health and Medical Research Council
Funding Amount
$466,980.00
Summary
Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotr ....Approximately 70% of infant death is associated with premature birth. Preterm birth occurs in 6-10% of pregnancies, and there has been no reduction in the rates of premature birth in the last 30 years. This is largely because we remain ignorant of how normal and abnormal birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotrophin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely a rise in CRH occurs earlier in the pregnancy and more rapidly, while in women who deliver late the rise occurs more slowly. This work has given rise to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this research project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done in two ways: (1) by examining the DNA sequences involved in controlling expression of the CRH gene and (2) by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and abnormal birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be invented.Read moreRead less
Special Research Initiatives - Grant ID: SR140100001
Funder
Australian Research Council
Funding Amount
$35,000,000.00
Summary
The Juvenile Diabetes Research Foundation Australian Type 1 Diabetes Research Network and Program. This Proposal continues the development of the initial Type 1 Diabetes Clinical Research Network (CRN), launched by JDRF in June 2011 with a $5m grant from the Australian Government.
The principal goal of the CRN is to positively impact the life of people with T1D in Australia through the support and promotion of clinical research. A further electoral commitment of $35m over 5 years will enable f ....The Juvenile Diabetes Research Foundation Australian Type 1 Diabetes Research Network and Program. This Proposal continues the development of the initial Type 1 Diabetes Clinical Research Network (CRN), launched by JDRF in June 2011 with a $5m grant from the Australian Government.
The principal goal of the CRN is to positively impact the life of people with T1D in Australia through the support and promotion of clinical research. A further electoral commitment of $35m over 5 years will enable further progress towards finding a cure for T1D, including delivering better and faster access to new therapies and treatments that can help prevent and manage the disease.
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Novel therapies to limit renal fibrosis in diverse models of renal disease. Kidney failure is a devastating health, social and financial outcome for the individual, their employer, family and the broader society, This project will carefully dissect mechanisms underpinning the scarring in the kidney that predisposes to kidney failure and will investigate novel therapies to prevent kidney damage.
Effect Of Sex Steroids, Inflammation, Environmental And Biopsychosocial Factors On Cardiometabolic Disease Risk In Men
Funder
National Health and Medical Research Council
Funding Amount
$1,817,271.00
Summary
Heart disease is more frequent and occurs at an earlier age in men than women. The reason is unknown. Apart from obesity and associated disturbances of metabolism, changes in sex hormones such as testosterone, together with the effects of inflammation may be important, and may in turn be affected by environment, lifestyle behaviours, and stress. To untangle these relationships, we will use cutting edge technology, in a large sample of men, in partnership with other international scientists.
Molecular Regulation Of CRH Gene Expression In The Human Placenta
Funder
National Health and Medical Research Council
Funding Amount
$70,285.00
Summary
Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormon ....Approximately 70% of infant death is a result of premature birth. Preterm delivery occurs in 6-10% of pregnancies, and there has been no reduction in this rate in the last 30 years. This is largely because we remain ignorant of how normal and preterm birth is controlled. Understanding the physiology of human pregnancy is a critical step in the development of ways to detect and prevent preterm birth. Our group has demonstrated a link between production of a hormone (corticotropin releasing hormone, CRH) in the placenta and the length of time the baby is carried in the mother. In women who will deliver prematurely the rise in CRH production occurs earlier and more rapidly, while in women who deliver late the rise occurs more slowly. This work has led to the concept of a biological clock that determines the length of time the fetus will be carried by the mother before birth, and in which production of CRH in the placenta plays a central role. We have been studying how the CRH gene is controlled in placental cells. We have discovered some regions in the DNA of the CRH gene which have important roles in controlling how much CRH is made by the placenta. The experiments described in this project will determine the molecular mechanisms that control the production of CRH in the human placenta. This will be done by examining the DNA sequences involved in controlling the CRH gene and by identifying the proteins that actually perform the regulating functions that result in either increased or decreased amounts of CRH being produced by the placenta. This important information will help us better understand how normal and preterm birth is controlled, and from that knowledge new ways to detect and prevent premature birth can be developed.Read moreRead less
Alpha-2-Macroglobulin And The Transport And Uptake Of The Hormone, Hepcidin
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
Hepcidin is a peptide hormone that is a major regulator of iron metabolism. It has been suggested that hepcidin is free in the blood. However, we recently identified that hepcidin binds with alpha-2-macroglobulin (a2-M) in the plasma and this increases the efficacy of this peptide. The demonstration that a2-M plays a role in hepcidin biology will lead to a better understanding of hepcidin physiology, the development of methods for its measurement and improved treatment of iron related diseases.
The Role Of The Intrauterine (pro) Renin-(pro)renin Receptor System In Prostaglandin Synthesis In Pregnancy.
Funder
National Health and Medical Research Council
Funding Amount
$488,478.00
Summary
Preterm birth is associated with a very high incidence of infant disability and mortality. This has long term economic and social costs to the Australian people. We will demonstrate that in late gestation, the intrauterine (pro)renin renin receptor system controls prostaglandin synthesis by the fetal membranes and the placenta. Prostaglandins can cause premature labour.
Gene therapy for islet transplantation. Improved understanding of aetiology of type I diabetes. Development of islet transplantation as a clinical therapeutic for type I diabetes. Improved efficacy of islet transplantation. Improved health for subjects with type I diabetes. Decreased diabetic complications. Improved quality of life for subjects with type I diabetes. Reduced burden on health system for management of diabetic complications for subjects with type I diabetes