EXAMINING THE RELATIONSHIP BETWEEN MATRIPTASE-2 AND HEMOJUVELIN, TWO ESSENTIAL REGULATORS OF IRON HOMEOSTASIS
Funder
National Health and Medical Research Council
Funding Amount
$533,541.00
Summary
The control of iron levels is important in health and well being. Too little can lead to iron deficiency and anaemia, conversly too much can lead to haemochromatosis and tissue damage. We will examine the role of two proteins, matriptase-2 and hemojuvelin that when mutated cause iron deficiency or iron overload respectively. We will study how these proteins interact and work in opposite directions to control iron levels. The results will help to develop new therapeutics for iron disorders.
Polarized Trafficking Of E-cadherin In Epithelial Cells.
Funder
National Health and Medical Research Council
Funding Amount
$515,564.00
Summary
The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to ....The cell adhesion protein E-cadherin is expressed in all epithelial tissues of the body where it has essential functions during development and in the adult in establishing and maintaining polarized cell monolayers. E-cadherin is also a vital tumour suppressor, its normal function guarantees that cells or even early tumours cannot metastasise; in contrast E-cadherin is always lost or malfunctions in malignant tumours. Earlier studies showed that E-cadherin is constantly moved, or trafficked, to and from the surface of epithelial cells. This trafficking has dual roles, firstly in delivering newly-made E-cadherin to the surface where it functions and secondly, in regulating its adhesive function. Our research in this project is focussed on the molecules and intracellular compartments that control the delivery of E-cadherin to the cell surface. E-cadherin must be sorted in order to be delivered to the correct side of the cell. Having previously discovered the sorting signal in E-cadherin, we will now identify the cognate adaptor protein(s) that accomplish this sorting. New imaging techniques allow us to study protein trafficking inside live cells. Such studies have recently revealed that E-cadherin passes through a recycling endosome compartment on its way to the cell surface. This unexpected route, and the structure and role of the recycling endosome will now be studied in detail in live cells. Finally we will compare the sorting and trafficking of E-cadherin with the closely-related N-cadherin protein, to determine whether there are inherent differences in their trafficking that could explain their opposite roles in tumour cells, where N-cadherin is substituted for E-cadherin and allows metastatic behaviour. These studies will provide important information for understanding the adhesive and tumour suppressive roles of E-cadherin. In addition our findings will generate information fundamental to our understanding of cell polarity and protein sorting.Read moreRead less
20 Year Study Of Skin Cancer In A Queensland Community
Funder
National Health and Medical Research Council
Funding Amount
$396,415.00
Summary
Skin cancers are by far the commonest cancers diagnosed in Australia. Even though it is known that sun exposure in excess causes skin cancers there are complexities about the causes, especially of basal cell carcinoma (BCC) -the major type of skin cancer- that are still not understood. Relative intensity of sun exposure and perhaps its timing with respect to age in life may well be critical factors. We aim to study these causes in very great detail by collating information that has been gathered ....Skin cancers are by far the commonest cancers diagnosed in Australia. Even though it is known that sun exposure in excess causes skin cancers there are complexities about the causes, especially of basal cell carcinoma (BCC) -the major type of skin cancer- that are still not understood. Relative intensity of sun exposure and perhaps its timing with respect to age in life may well be critical factors. We aim to study these causes in very great detail by collating information that has been gathered over a 20 year period in a community-based skin cancer study in Nambour, Qld as well as performing some laboratory tests on skin cancer tissue collected from participants. This 3-year project will enable the full realisation of the potential of this esource-20 years in the making- with its wealth of information for answering questions about skin cancer decelopment and preventability. It should finally provide us with a clearer rationale for 'prevention of skin cancer' than is currently available. In addition we shall assess the costs of treatment of skin cancer in general and for the individual, and how much preventive practices for skin cancer might save the health budget, by using the releavnt data collected from this community sample.Read moreRead less
Mothers' History Of Mental Health Impairment And Its Impact During Mid-Life
Funder
National Health and Medical Research Council
Funding Amount
$421,580.00
Summary
There have been few specific studies of the health of women in mid-life. In mid-life, mental health impairment and health problems associated with biological and social transitions (e.g. menopause) are major concerns. National estimates indicate that between 15% and 20% of women in the mid-life age range have experienced a mental illness in the past year. The proportion of women experiencing a combination of emotional and physical symptoms, frequently associated with the menopause, is likely to ....There have been few specific studies of the health of women in mid-life. In mid-life, mental health impairment and health problems associated with biological and social transitions (e.g. menopause) are major concerns. National estimates indicate that between 15% and 20% of women in the mid-life age range have experienced a mental illness in the past year. The proportion of women experiencing a combination of emotional and physical symptoms, frequently associated with the menopause, is likely to be somewhat higher. This proposal involves merging information collected initially from 1981 onwards, with data on the mother's mental and physical health, to be collected in this follow-up. Women in this study (8556) were enrolled at their first obstetrical visit and they have been followed up shortly after the birth, when the child was 6 months, 5 years and 14 years. On each occasion extensive information has been obtained on the mother's mental and physical health, as well as on the child's health and development. This study will examine the chronicity of the mother's mental health symptoms over a 21-year period, and assess the association between her early mental health, the child's health and her current health status. This is the only large Australian cohort study to have followed a sample of women for 21 years. It will permit us to understand more of how women's health changes over time and the factors associated with these changes. It will provide the first large-scale study of factors influencing women's health transition through the menopause.Read moreRead less