A New Paradigm For Class I Cytokine Receptor Activation
Funder
National Health and Medical Research Council
Funding Amount
$954,946.00
Summary
Class I cytokine receptors include around 30 receptors with diverse functions such as controlling metabolism and inflammation. Cytokine receptors are molecular switches on cells that receive signals from other cells and transmit this signal into the cell’s nucleus to control the regulation of genes. This project will determine the molecular mechanisms involved in class I cytokine receptors and use this knowledge to develop novel ways to modulate these receptors for clinical applications.
Role Of STAT5 In Defining Lifespan In Mouse Models
Funder
National Health and Medical Research Council
Funding Amount
$547,216.00
Summary
We seek to elucidate the molecular basis for the extended lifespan seen in the Methuselah mouse, the longest lived mouse model of ageing. This mouse lacks the receptor for growth hormone, and we have identified a major gene-regulating protein activated by the growth hormone receptor as correlating with lifespan. This project seeks to establish if this protein does indeed regulate lifespan, and to determine how it does this, particularly in relation to metabolism of toxins and free radicals.
The Role Of Cellular Microdomains In G-protein Coupled Receptor Signalling.
Funder
National Health and Medical Research Council
Funding Amount
$385,297.00
Summary
Molecules communicate with cells by attaching to proteins called receptors on the outside of cells, and triggering a series of events inside the cell. These events initially include the assembly of multiple proteins at the cell surface. This project will examine the formation of receptors and other proteins into these ‘communication complexes’. This will provide novel targets for more selective drug development.
From Endoderm To Gut: Regulation Of Lineage Allocation And Morphogenesis In The Murine Embryo
Funder
National Health and Medical Research Council
Funding Amount
$439,500.00
Summary
One of the most critical steps in early development is the generation of the full complement of cell types required to build the embryo. A thorough understanding of the mechanisms underlying this is vital for the development of methods for directing the differentiation of stem cells for use in regenerative medicine. The objective of our research is to understand the cellular and molecular mechanisms underlying the assignment of cells to particular fates and the establishment of the body plan of ....One of the most critical steps in early development is the generation of the full complement of cell types required to build the embryo. A thorough understanding of the mechanisms underlying this is vital for the development of methods for directing the differentiation of stem cells for use in regenerative medicine. The objective of our research is to understand the cellular and molecular mechanisms underlying the assignment of cells to particular fates and the establishment of the body plan of the embryo. The endodermal cell layer forms the lining of the embryonic gut which gives rise to the entire gastrointestinal tract, the respiratory tract and other structures including the liver and the pancreas during organogenesis. This investigation focuses on the questions of how the pluripotent progenitor cells are allocated to the endodermal lineage and how the embryonic gut is patterned during early development of the mouse embryo. Analysis of endoderm development will provide insights into the roles of the allocation of progenitor cells to tissue lineages, cell movement, and diversification and maturation of functional cell types. These processes are universally relevant to the formation of all types of organ primordia in the embryo. Understanding the complexity of tissue interactions and the interplay of molecular mechanisms of cell lineage choice and differentiation in the embryo is a major challenge. However, knowledge of the processes that drive tissue differentiation in the embryo is absolutely crucial for enhancing our ability to direct cell and tissue differentiation for the realization of cell-based technologies in biomedicine.Read moreRead less
One of the most critical steps in embryonic development is the assembly of the different tissue components into a three-dimensional structure in order to build a major body part of the foetus. In the development of the head, this form-shaping process undertaken by different cell populations is coordinated by genetic activity that is triggered by signals received by cells. The objective of our research is to understand how one of the many signalling mechanisms, WNT signalling, works in making the ....One of the most critical steps in embryonic development is the assembly of the different tissue components into a three-dimensional structure in order to build a major body part of the foetus. In the development of the head, this form-shaping process undertaken by different cell populations is coordinated by genetic activity that is triggered by signals received by cells. The objective of our research is to understand how one of the many signalling mechanisms, WNT signalling, works in making the head and face of the embryo. We will study the development of embryos of mice in which mutations have been introduced experimentally in genes that code for factors of the WNT signalling pathway. Understanding the complexity of tissue interactions and the interplay of molecular mechanisms of head formation in the embryo is a major challenge. However, knowledge of the processes in animal models will contribute to a better delineation of the role of signalling in normal head development. It will also help to direct the focus of future clinical investigations to the most relevant genetic determinants of birth defects of the head and face, which is present in about 8 per 10,000 births in Australia.Read moreRead less
The Contribution Of Gp130-Stat3 During Wnt-beta-catenin Induced Intestinal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$396,275.00
Summary
There is growing evidence that cancer is initiated and develops not by the deregulation of a single gene or signaling pathway, but by multiple events. We will study the co-operation between two pathways - gp130-Stat and Wnt. These signaling pathways are frequently deregulated in many types of cancer, however their interaction remains poorly understood. We shall explore their mechanism of interaction during intestinal cancer in order to develop a novel therapeutic target for this disease.
Characterising The Physiological Roles Of The Asparaginyl Hydroxylase FIH-1 In Development And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$274,743.00
Summary
FIH-1 is an oxygen-sensing protein expressed in every cell. The ability for cells to detect and respond to oxygen deficiency is necessary for survival in heart disease and stroke, and is also a feature of cancer. This research aims to characterise the role FIH-1 plays in normal development and disease using mouse and tumour model systems. This research could ultimately indicate whether FIH-1 is a feasible drug target.