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 Persisting Vascular Effects Of Activation Of The Renin-Angiotensin System
Funder
National Health and Medical Research Council
Funding Amount
$628,456.00
Summary
Heart attacks and strokes are the major cause of death and disability in Australians. Heart disease is widely viewed to be the legacy of our diet and lifestyle, and even that of our parents. We propose to explore in detail the molecular mechanism of how this imprinting comes about and identify new targets to prevent, retard or reverse heart disease.
Neural Control Of Renin Expression By MicroRNA In Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$805,972.00
Summary
We identified that mice bred to have high blood pressure have an overactive nervous system that affects a gene that controls a hormone in the kidney that increases blood pressure. The proposal will determine the effects of a novel treatment to alter the gene to reverse the changes in the kidney and thereby normalizing blood pressure. This will lead to new therapy and reduce the major risk factor of cardiovascular disease.
Type 2 diabetes is a health crisis in Australia. In this project, we will investigate the mechanisms whereby high glucose and fat impair pancreatic beta-cell function leading to type 2 diabetes. We will establish how endoplasmic reticulum stress and the protein Id1 are linked with loss of beta-cell gene expression and function. The information gained will further our understanding of the basic mechanisms regulating insulin secretion and provide new therapeutic targets for diabetes treatment.
Maternal Recognition Of Fetal Sex In The Regulation Of Labour
Funder
National Health and Medical Research Council
Funding Amount
$455,821.00
Summary
Preterm birth is the largest cause of death in infants and males are more likely to be born preterm than females. We propose that the intrauterine renin-angiotensin system, the activity of which is regulated in a sex-specific manner, plays a critical role in protecting against preterm labour. Our study will further our understanding of the mechanisms of preterm labour and provide new insight into the sex-specific differences in the prevalence of preterm birth.
Interactions Between RAGE And The Type 1 Angiotensin Receptor Determine The Pro-atherosclerotic Actions Of Angiotensin II
Funder
National Health and Medical Research Council
Funding Amount
$521,956.00
Summary
Heart attacks and strokes are a major cause of death and disability in Australians. Activation of the renin angiotensin system plays a key role in the development and progression of atherosclerosis, the process that leads to narrowing and obstruction of arteries. In preliminary data we have found a way to block these pathways without affecting the control of blood pressure. We believe that interventions based on these data will be important for the prevention and treatment of heart disease.
Altered Protein Secretion Links The Fatty Liver To Metabolic Disease
Funder
National Health and Medical Research Council
Funding Amount
$415,797.00
Summary
The liver secretes proteins to alter metabolism in other tissues of the body. Fatty liver is a major feature of obesity and type 2 diabetes. This project aims to understand how fatty liver changes protein secretion and how this impacts on metabolic processes. The outcomes of this project will be the identification of protein biomarkers of fatty liver and the prediction of insulin resistance development in other tissues of the body.
Investigating The Novel Role Of SEPS1 In The Prevention Of Islet Beta Cell Failure And Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$535,804.00
Summary
SEPS1 is an important glucose-regulated protein whose function is to protect tissues from oxidative stress. Inhibition of SEPS1 by hyperglycaemia, is a mechanism for progression of Type 1 and Type 2 diabetes once hyperglycaemia supervenes. The overall aim of the project is to investigate the function of the novel SEPS1, using transgenic and knockout approaches.
New Molecular Mechanisms Of Islet Protection Against Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$673,259.00
Summary
Type 2 diabetes is an enormous health and economic burden. The mechanisms of ?-cell compensation for insulin resistance and of ?-cell failure in type 2 diabetes are unclear. This proposal will test the novel hypothesis that the adaptation of endoplasmic reticulum (ER) capacity mediates ?-cell compensation, and that the failure of ?-cell adaptation to ER stress causes diabetes. The studies will show that targeting ER capacity is an important novel strategy for type 2 diabetes therapy.
Reversal Of Diabetes In A Humanised Mouse Using A Clinically Applicable Vector System
Funder
National Health and Medical Research Council
Funding Amount
$842,173.00
Summary
Somatic gene therapy is one of the strategies that is being considered to cure Type I diabetes. Specifically, we wish to engineer liver cells to replace beta cell function. The aim of this project is to design a clinically-applicable protocol for the reversal of diabetes using a recombinant adeno-associated vector that delivers genes to human livers with high efficiency showing long term expression without pathogenicity and immunogenicity following a simple intra-peritoneal injection.