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
LKB1 - The Link Between Obesity And Breast Cancer In Postmenopausal Women
Funder
National Health and Medical Research Council
Funding Amount
$292,216.00
Summary
Obesity is a worldwide epidemic affecting 60% of Australians and is linked to many diseases including breast cancer. Changes in sex hormone levels during menopause may cause these diseases. The focus of this proposal is to determine the role of the sex hormones to regulate a protein (LKB1) involved in both fat metabolism and cancer. This research will benefit the ageing population by making a contribution toward generating therapeutics to combat obesity and breast cancer.
Pathways For Estrogen Feedback To Gonadotropin Releasing Hormone Neurons
Funder
National Health and Medical Research Council
Funding Amount
$466,980.00
Summary
Gonadotropin releasing hormone (GnRH) is the brain hormone that drives the reproductive process. In the female, a surge in the secretion of GnRH is the trigger for ovulation. An understanding of the mechanisms that regulate the secretion of GnRH is, therefore, extremely important if we are to decipher abnormalities that lead to infertility. Understanding of the ovulatory process is also important for the development of new (possibly simpler) means of contraception. Our research is intended to pr ....Gonadotropin releasing hormone (GnRH) is the brain hormone that drives the reproductive process. In the female, a surge in the secretion of GnRH is the trigger for ovulation. An understanding of the mechanisms that regulate the secretion of GnRH is, therefore, extremely important if we are to decipher abnormalities that lead to infertility. Understanding of the ovulatory process is also important for the development of new (possibly simpler) means of contraception. Our research is intended to provide a full understanding of the brain circuits that provide input to the GnRH neurons. In particular, we will focus on the microcircuitry in the preoptic area, where GnRH cells are found. In addition to providing a full understanding of the circuits that are primarily involved in regulating GnRH secretion, this work will provide a substrate upon which we can expand knowledge of how factors such as emotion and stress can impact on the reproductive process.Read moreRead less
I am a cellular physiologist investigating the role of ion channels, receptors and intracellular signalling systems in the control of hormone secretion from endocrine cells, contraction of cardiac myocytes and to a lesser extent, growth of endometrium can
Structural And Functional Investigation Into The Cooperation Of IGF And Vitronectin-binding Receptors In Cell Migration
Funder
National Health and Medical Research Council
Funding Amount
$239,250.00
Summary
Breast cancer is the most commonly diagnosed form of cancer in Australian women, accounting for 26% of diagnosed cancers and 21% of cancer deaths among women. One in fourteen Australian and one in nine women worldwide will develop breast cancer in their lifetime. Significantly, approximately one in four of those diagnosed will die from their disease. The primary factor that determines survival is early diagnosis and treatment. Indeed, the primary tumour itself rarely causes death. Rather, the di ....Breast cancer is the most commonly diagnosed form of cancer in Australian women, accounting for 26% of diagnosed cancers and 21% of cancer deaths among women. One in fourteen Australian and one in nine women worldwide will develop breast cancer in their lifetime. Significantly, approximately one in four of those diagnosed will die from their disease. The primary factor that determines survival is early diagnosis and treatment. Indeed, the primary tumour itself rarely causes death. Rather, the dissemination of tumour cells to remote sites and the establishment of secondary tumours in critical sites in the body is the major mechanism of mortality. An understanding of the processes that lead to the establishment of secondary tumour bodies and strategies to halt the spread of cancer beyond the primary site are therefore highly valuable. Two factors thought to be pivotal in breast cancer metastasis are altered interactions with the microenvironment surrounding cells and exposure to increased levels of hormones and growth factors, such as the insulin-like growth factors (IGFs). We have recently found that IGFs form complexes with a protein called vitronectin, found in the microenvironment, and these complexes can stimulate increased migration of breast cancer cells. This project will examine the interaction of IGF and VN in stimulating cell migration and in particular, aims to identify the genes involved in the enhanced cell migration. In addition we will examine how the IGF:vitronectin complexes form and how these in turn interact with receptors on the surface of the cell. The data obtained will provide critical fundamental information that is necessary to develop targeted therapies for the treatment and control of breast cancer.Read moreRead less