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The Unfolded Protein Response In Inherited Musculoskeletal Disease - Mechanisms And Therapeutic Strategies
Funder
National Health and Medical Research Council
Funding Amount
$643,607.00
Summary
In genetic diseases, gene mutations commonly cause proteins to fold abnormally. This can cause cell stress resulting in cell death. Our studies will determine the role of cell stress in a clinically important group of debilitating inherited bone and cartilage diseases caused by collagen mutations. Our studies will explore the mechanisms of how this stress causes the disease, but importantly will translate these findings by testing a new therapeutic strategy strengthen bones in brittle bone disea ....In genetic diseases, gene mutations commonly cause proteins to fold abnormally. This can cause cell stress resulting in cell death. Our studies will determine the role of cell stress in a clinically important group of debilitating inherited bone and cartilage diseases caused by collagen mutations. Our studies will explore the mechanisms of how this stress causes the disease, but importantly will translate these findings by testing a new therapeutic strategy strengthen bones in brittle bone disease.Read moreRead less
Despite the high mortality associated with colon cancer only limited therapy options are available to treat these cancers. Here we propose a new strategy for inhibiting colon cancers driven by a specific type of mutations. Our preliminary data show that loss of DNA encoding a tumor suppressor gene creates a unique vulnerability in colon cancers. The aim of this proposal is to exploit this vulnerability as a strategy for combating colon cancer.
The proposal focuses on a novel angle explaining how pancreatic beta cells normally match their insulin synthesis, storage and secretion in response to an enhanced demand as occurs during obesity, and how this fails in the progression to Type 2 diabetes. In particular we will expand our discovery that glucose rapidly enhances the synthesis of a novel factor regulating gene transcription. This will generate basic knowledge that will potentially help design of novel therapies for Type 2 diabetes.
The Obesity Prone Oocyte- Causes, Consequences, Treatments
Funder
National Health and Medical Research Council
Funding Amount
$516,159.00
Summary
Obesity is perpetuated from mothers to offspring, in part due to changes in the oocyte (egg) that affect embryo growth. We have discovered that obesity causes changes in the mitochondria (the energy producers) of the egg. We hypothesise this causes long-lasting changes to embryo metabolism and will test, in mice, novel treatments to reverse the detrimental effects. The project will show how obesity affects embryo metabolism and growth, and determine whether defects can be prevented by drugs or l ....Obesity is perpetuated from mothers to offspring, in part due to changes in the oocyte (egg) that affect embryo growth. We have discovered that obesity causes changes in the mitochondria (the energy producers) of the egg. We hypothesise this causes long-lasting changes to embryo metabolism and will test, in mice, novel treatments to reverse the detrimental effects. The project will show how obesity affects embryo metabolism and growth, and determine whether defects can be prevented by drugs or lifestyle changes.Read moreRead less
Graves’ disease is the most common cause of hyperthyroidism. It leads to long-term impairments in quality of life and has a 40% higher mortality rate compared with the general population. We know surprisingly little about the causes of Graves’ disease. One possible trigger is stressful life events; however, the relationship is yet to be proven. This study will assess whether stressful life events, specifically military deployment, are associated with Graves’ disease.
Consequences Of Elevated Maternal Glucocorticoids For Early Childhood Renal Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$605,190.00
Summary
A growing body of evidence links maternal stress, such as that precipitated by financial problems or relationship issues (marriage break-up, physical or emotional abuse), with preterm birth and low-birth weight, which in turn has been linked to increased risk of adult disease. Our studies examine how maternal stress impacts on kidney development in childhood and sets the child on the path to cardiovascular disease in adulthood.
Interactions Between The Serotonin Transporter And Sympathetic Nervous Activation In Patients With Major Depressive Disorder - Understanding The Link Between The Brain And The Heart
Funder
National Health and Medical Research Council
Funding Amount
$527,109.00
Summary
There is evidence that patients with major depressive disorder (MDD) are at increased risk of developing heart disease. While the mechanisms responsible remain unknown we have previously demonstrated that cardiac sympathetic nervous activity in patients with MDD follows a bimodal distribution, with values in some patients being extraordinarily high. In this project we will determine the physiological consequences of sympathetic activation in patients with MDD.
MicroRNA serves as critical factors in diverse biological events. However, it remains poorly understood how microRNAs contribute to the regulation of lifespan and age-associated changes, such as alterations in metabolic activity and an increased incidence of disorders. We aim to understand how microRNAs regulate stress response pathways and caloric restriction-mediated lifespan extension using the nematode Caenorhabditis elegans, an excellent model organism for ageing biology.
The Effect Of Hypochlorite On The Toxicity And Clearance Of The Alzheimer’s Disease-associated Amyloid Beta Peptide
Funder
National Health and Medical Research Council
Funding Amount
$461,496.00
Summary
Alzheimer’s disease (AD) is the leading cause of dementia worldwide and a growing burden on our aging society. Recent studies support the idea that in AD a deleterious relationship exists between inflammation in the brain and the accumulation of amyloid beta (A?), a peptide with toxic properties. This proposal aims to examine the details of this relationship with a focus on the toxicity and clearance of A? when it is modified by hypochlortie, a chemical that is generated during inflammation.
Norovirus Infection At The Stress Granule-PKR-p-elF2α Axis
Funder
National Health and Medical Research Council
Funding Amount
$505,967.00
Summary
This project application will aim to investigate and understand how viruses that cause vomiting and diarrhoea are able to infect, proliferate and spread within the human body. It aims to address how viruses are able to avoid and replicate in the presence of an effective immune response. We have evidence showing that Noroviruses are able to exploit certain antiviral proteins to paradoxically aid in virus replication and survival.