Role Of IGF Binding Protein-3 (IGFBP-3) And IGFBP-5 As Modulators Of Nuclear Hormone Signalling
Funder
National Health and Medical Research Council
Funding Amount
$465,750.00
Summary
The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain ....The insulin-like growth factors are small proteins involved in the growth of most tissues. Their actions are regulated by binding to larger proteins (known as IGFBPs) in the bloodstream and outside the cell. However, some IGFBPs are also found inside cells, where they seem to carry out other functions. We believe that two of these binding proteins, IGFBP-3 and IGFBP-5, change the way cells respond to vitamin A and vitamin D. These two vitamins are important in cell growth and in the way certain cells perform specialised functions. In test-tube experiments, IGFBP-3 and IGFBP-5 interact directly with the receptors that regulate the effects of these hormones. If the same thing happens inside the cell, IGFBP-3 and IGFBP-5 could change the way these receptors respond to signals from outside the cell. We will investigate what effect these IGFBPs have in living cells and in whole animals and how this may relate to human disease. If we are able to understand how IGFBP-3 and IGFBP-5 affect the way cells respond to vitamin A and D, then we may be able to develop new ways to treat certain human diseases.Read moreRead less
E-Cadherin Endocytosis In Morphogenesis: Recycling And Growth Factor Induced Uptake.
Funder
National Health and Medical Research Council
Funding Amount
$498,088.00
Summary
E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell ....E-cadherin is a cell-cell adhesion protein expressed in all epithelia with essential roles in establishing cell polarity and in tissue patterning during development. In the adult, E-cadherin functions to maintain epithelial integrity. E-cadherin is also a vital tumour suppressor, protecting cells against metastatic transformation. Our earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. The endocytosis or internalisation of cell surface E-cadherin serves to regulate its role in adhesion. More recently, we and others have shown that E-cadherin is endocytosed in response to growth factors, in conjunction with the activated growth factor receptors themselves. E-cadherin can influence the trafficking and signaling of these receptor tyrosine kinases. This joint endocytosis is an elegant mechanism for the simultaneous downregulation of cell adhesion and activation of signaling for cell growth and motility. The growth and differentiation of epithelial cells during tissue patterning or morphogenesis relies critically on these endocytic pathways. Our research is aimed at defining the endosomes and cellular machinery involved in E-cadherin-receptor endocytosis, moreover we will pursue initial findings suggesting that there are different pathways and fates for E-cadherin endocytosed at the behest of different growth factors. We will study endocytosis during the processes of epithelial cyst formation and tubulation of cysts as an in vitro model for mammalian morphogenesis. These studies will provide important and novel information for understanding the roles of E-cadherin in adhesion and in growth factor signaling during epithelial morphogenesis. Ultimately these findings will be of relevance to epithelial development and the prevention of cancer.Read moreRead less
Cancers of the skin are the most common tumours in humans, and their diagnosis and treatment impose the largest costs on Australia’s cancer budget. While much has been learned about the roles of sunlight and skin type as risk factors for skin cancer, relatively little is known about the genes conferring risk. This study will compare the genetic profiles of over 6000 patients with skin cancer to 3000 people without skin cancer to pinpoint the genes responsible for skin cancer.
Prevalence Of Dementia In The Torres Strait And Common Health Issues Of Later Life In The Torres Strait
Funder
National Health and Medical Research Council
Funding Amount
$365,000.00
Summary
The aim of the project is to assess the prevalence of dementia in people aged 45 years and over living in Torres Strait Islander communities and identify potential risk and protective factors associated with dementia risk. An additional aim is to revalidate a culturally appropriate cognitive assessment tool, the Kimberley Indigenous Cognitive Assessment (KICA) for use in the Torres Strait.
Prospective Imaging Study Of Ageing: Genes, Brain & Behaviour
Funder
National Health and Medical Research Council
Funding Amount
$6,465,047.00
Summary
While the burden of dementia in Australia occurs late in life, the underlying brain disease accumulates for decades prior to dementia onset. Disease modifying interventions have the greatest potential to avert later disease burden if introduced during this crucial window, well before the onset of clear cognitive decline. To reduce Australia's future dementia burden, it is thus imperative to identify those Australians at risk of dementia whilst they are still relatively young.
Enhancing aquaculture production of the tropical abalone using complementary genetic and environmental approaches. While temperate abalone are one of our most valuable seafoods, there is a growing demand worldwide for the ?cocktail?-sized tropical abalone Haliotis asinina. Australia is well positioned to capture the market for this rapidly growing species. We propose to enhance the already favourable growth rates of Haliotis asinina in aquaculture by delineating critical environmental and geneti ....Enhancing aquaculture production of the tropical abalone using complementary genetic and environmental approaches. While temperate abalone are one of our most valuable seafoods, there is a growing demand worldwide for the ?cocktail?-sized tropical abalone Haliotis asinina. Australia is well positioned to capture the market for this rapidly growing species. We propose to enhance the already favourable growth rates of Haliotis asinina in aquaculture by delineating critical environmental and genetic factors that effect production. This proposal uniquely melds commercial production practices at MG Kailis Export Pty Ltd with expertise in aquaculture and marine biotechnology present at The University of Queensland and CSIRO Marine Research. This knowledge will enhance the development of this new aquaculture industry in tropical Australia.Read moreRead less
The Aetiology Of Alcohol Use Disorders In Adulthood: A Generational Perspective
Funder
National Health and Medical Research Council
Funding Amount
$630,927.00
Summary
This study aims to investigate the causes of alcohol problems in adult Australians. We will follow-up participants from a birth cohort study who are now in their thirties. We will assess long term outcomes from in-utero exposure to alcohol and biological, developmental and genetic predictors of alcohol disorders in adulthood. This study also aims to study genetic factors which may be important in the development of alcohol abuse and dependence.
Which Modifiable Risk Factors Actually Cause Cancer?
Funder
National Health and Medical Research Council
Funding Amount
$384,076.00
Summary
Observational studies suggest that modifiable risk factors such as low vitamin D levels, coffee consumption, alcohol consumption and obesity may be important in cancer risk. However, observational studies can only demonstrate association between a risk factor and cancer, and association does not equal causation. We present an alternative approach to help determine which risk factors actually cause cancer.