L-amino Acid Sensing By The Extracellular Calcium-sensing Receptor: Molecular, Cellular And In Vivo Studies
Funder
National Health and Medical Research Council
Funding Amount
$362,545.00
Summary
Recent work by Dr Conigrave and colleagues demonstrates for the first time that protein and calcium metabolism are linked at the molecular level by the widely distributed calcium-sensing receptor. The project will aim to demonstrate the physiological significance of this finding by testing whether L-amino acids, the building blocks of body protein, exert receptor-dependent control over the secretion and blood levels of hormones that regulate body calcium levels. It will further test the hypothes ....Recent work by Dr Conigrave and colleagues demonstrates for the first time that protein and calcium metabolism are linked at the molecular level by the widely distributed calcium-sensing receptor. The project will aim to demonstrate the physiological significance of this finding by testing whether L-amino acids, the building blocks of body protein, exert receptor-dependent control over the secretion and blood levels of hormones that regulate body calcium levels. It will further test the hypothesis by determining whether amino acids exert receptor-dependent control over the proliferation of bone forming cells and urinary excretion of calcium.Read moreRead less
Parathyroid Tumorigenesis - A Role For The Newly Identified Putative Tumour Suppressor HRPT2
Funder
National Health and Medical Research Council
Funding Amount
$432,750.00
Summary
Primary hyperparathyroidism is one of the most common tumour associated diseases of hormone secreting glands affecting 0.1-0.5% of adults and up to 3.4% of post-menopausal women. It can occur in family members, either alone or with other tumours, and can also occur with no family history (sporadic). Hyperparathyroidism is caused by secretion of excessive levels of parathyroid hormone. Amongst other problems, this causes significant bone disease that can lead to fracture. What is going wrong at t ....Primary hyperparathyroidism is one of the most common tumour associated diseases of hormone secreting glands affecting 0.1-0.5% of adults and up to 3.4% of post-menopausal women. It can occur in family members, either alone or with other tumours, and can also occur with no family history (sporadic). Hyperparathyroidism is caused by secretion of excessive levels of parathyroid hormone. Amongst other problems, this causes significant bone disease that can lead to fracture. What is going wrong at the genetic level to cause this disease is, in most cases, poorly understood. In Hyperparathyroidism Jaw Tumour Syndrome (HPT-JT), one form of familial hyperparathyroidism, we and our international collaborators have recently identified mutations in the gene HRPT2 predicted to lead to loss of function of this gene. HRPT2 has no known similarities to other genes that may give hints as to its function. The overall aim of this project is to test our theory that HRPT2 has an important role in abnormal growth of parathyroid tissue that, in some cases, will lead to cancer. Further, we hypothesise that this gene will have a role in both familial and sporadic presentations of parathyroid disease. We will investigate this gene in parathyroid tumour specimens from patients with familial and sporadic disease for gene mutations and also different levels of gene expression. We will also explore a mechanism for how these mutations may function to cause disease and look at the effect of reduced HRPT2 expression on expression of thousands of other genes using a technique known as microarray analysis. The expected outcomes of this study include the identification of individuals at risk of developing cancer whose treatment will be tailored to their genetic profile. Characterisation of HRPT2, and the genes its expression influence, may lead to the identification of suitable targets for future treatment of hyperparathyroidism and its effects on bone disease.Read moreRead less
A Solution To The Parathyroid Gland Secretion Problem
Funder
National Health and Medical Research Council
Funding Amount
$508,003.00
Summary
Parathyroid hormone is the master hormone regulator of whole body calcium metabolism and a powerful new treatment for osteoporosis but the mechanism by which its natural secretion is controlled has never been solved. In this project we will apply new insights and advanced technical approaches to resolve this most fundamental question of calcium homeostasis, namely how parathyroid hormone secretion is controlled.
Engendering Biased Signalling At The Human Calcium Sensing Receptor (CaSR) To Correct Pathophysiology
Funder
National Health and Medical Research Council
Funding Amount
$633,860.00
Summary
The human calcium sensing receptor (CaSR) has been targeted therapeutically in hyperparathyroidism and osteoporosis, but current CaSR therapeutics exhibit problematic side effects or are ineffective. Thus, the current research proposal seeks to understand the specific properties of CaSR drugs required to selectively control whole body calcium and bone mineral metabolism, to identify ligands that can mediate desired therapeutic effects at the exclusion of adverse effects.
Molecular Determinants Of Amino Acid-dependent Signalling By The Calcium-sensing Receptor
Funder
National Health and Medical Research Council
Funding Amount
$566,035.00
Summary
Amino acids are the building blocks of proteins and an alternative energy source to carbohydrate and fat. Proteins are major structural components of our bodies. They also fulfil an amazing diversity of cellular and bodily functions acting, for example, as enzymes (biological catalysts), receptors, molecular chaperones and biological machines. Thus, amino acids are key nutrients and the human body has developed mechanisms for tightly regulating cellular responses depending upon their levels in b ....Amino acids are the building blocks of proteins and an alternative energy source to carbohydrate and fat. Proteins are major structural components of our bodies. They also fulfil an amazing diversity of cellular and bodily functions acting, for example, as enzymes (biological catalysts), receptors, molecular chaperones and biological machines. Thus, amino acids are key nutrients and the human body has developed mechanisms for tightly regulating cellular responses depending upon their levels in blood. Identifying amino acid sensing molecules and identifying the mechanisms they use to control cellular responses is thus a key issue in human biology. The applicant identified the calcium-sensing receptor as an amino acid sensor and has shown that this receptor provides a means by which fluctuations in amino acid levels regulate the secretion of the key calcium-regulating hormone, PTH. In the current proposal, the mechanisms that link amino acid activation of the calcium-sensing receptor to its key cellular responses will be determined.Read moreRead less
Teachers' professional development, communities of practice, and the secondary school subject department: The case of health and physical education. Schools are significant sites of authentic learning for teacher professional development. This study will contribute to a better understanding of how the culture of the secondary school subject department can facilitate or hinder such development. The project will: contribute to creating more supportive work contexts for teachers thereby reducing te ....Teachers' professional development, communities of practice, and the secondary school subject department: The case of health and physical education. Schools are significant sites of authentic learning for teacher professional development. This study will contribute to a better understanding of how the culture of the secondary school subject department can facilitate or hinder such development. The project will: contribute to creating more supportive work contexts for teachers thereby reducing teacher attrition; inform the development of better polices and practices surrounding teachers' professional learning communities; contribute to national and state level initiatives for the articulation of professional standards for teaching; and optimise the professional practices of HPE teachers who, as 'allied health workers', are integral to addressing Australia's health priorities.Read moreRead less
Scholarship in Science Teaching: an examination of the relationships between science content, teaching and learning. Excellent science teachers have profound impact on the students they teach. A central core of their excellence is the intertwined understandings they have of the content they teach and pedagogies for teaching this (termed pedagogical content knowledge). This knowledge is largely implicit, and hence not available to others. This research will develop enhanced methodologies to doc ....Scholarship in Science Teaching: an examination of the relationships between science content, teaching and learning. Excellent science teachers have profound impact on the students they teach. A central core of their excellence is the intertwined understandings they have of the content they teach and pedagogies for teaching this (termed pedagogical content knowledge). This knowledge is largely implicit, and hence not available to others. This research will develop enhanced methodologies to document and disseminate the knowledge of practice that underpins claims of professional excellence. Such research is crucial to the national and international moves to recognise, articulate, document, justify/validate, and share professional teaching excellence.Read moreRead less
Investigating ways to enhance teachers' science explanations and students' concept learning using cycles of reflective explanations. Explanation is central to learning because teachers explain phenomena to students and students are assessed on their explanations to other students and the teacher. Teacher explanations are not always effective and many lower secondary students provide descriptions when an explanation is needed. This projects aims for three outcomes: first, it researches teacher ....Investigating ways to enhance teachers' science explanations and students' concept learning using cycles of reflective explanations. Explanation is central to learning because teachers explain phenomena to students and students are assessed on their explanations to other students and the teacher. Teacher explanations are not always effective and many lower secondary students provide descriptions when an explanation is needed. This projects aims for three outcomes: first, it researches teacher explanations for teachers. Second, it researches student-student and student-teacher explanations to find which explanatory types maximise concept learning; and third, it evaluates a cycle of reflective explanations model for enhancing science teacher explanations.Read moreRead less