The Structural Basis Of Cytokine Signalling Inhibition
Funder
National Health and Medical Research Council
Funding Amount
$239,473.00
Summary
Cell-cell communcation is vital for the correct functioning of the body. Cells need to be told the correct time to divide, to produce certain enzymes or chemicals, to migrate and also when to apoptose, or die. Cells receive these signals through the binding of small soluble proteins called cytokines. Cytokines bind to specialized receptors on the surface of the cell and initiate an intracellular signaling cascade that passes the correct message to the nucleus. It is important that cells react to ....Cell-cell communcation is vital for the correct functioning of the body. Cells need to be told the correct time to divide, to produce certain enzymes or chemicals, to migrate and also when to apoptose, or die. Cells receive these signals through the binding of small soluble proteins called cytokines. Cytokines bind to specialized receptors on the surface of the cell and initiate an intracellular signaling cascade that passes the correct message to the nucleus. It is important that cells react to these protein messengers however it is just as vital that they don't overreact. Many human diseases, especially inflammatory diseases such as rheumatoid arthritis and type II diabetes, are due to aberrant cytokine signaling. To ensure this doesn't occur, cells have evolved a mechanism to quickly switch off the signaling cascade after it has started. This mechanism involves an entire family of proteins, the Suppressors of Cytokine Signalling (SOCS) family. These proteins can act via two distinct mechanisms. The first is to directly block the JAK-STAT proteins, proteins that initiate the intracellular part of the signaling cascade. The second mechanism has been less well studied, it involves the SOCS proteins upregulating the degradation of signaling intermediates. The SOCS proteins can do this through the action of a 40 residue domain called the SOCS box. The SOCS box directs proteins bound to other domains of the SOCS proteins to be degraded by interacting with a complex called an E3 ubiquitin ligase. This project involves determining the three-dimensional atomic structure of the SOCS-E3 ligase interaction and investigating biophysical aspects of the interaction. This information will lead to a fuller understanding of the mechanism of signaling inhibition and will provide information crucial to the design of SOCS inhibitors. Such inhibitors would be therapeutically important in the treatment of a number of human diseases such as cancer, arthritis and type II diabetes.Read moreRead less
The Role Of Alpha-haemoglobin Stabilising Protein In Haemoglobin Production And As A Therapeutic For Thalassaemia.
Funder
National Health and Medical Research Council
Funding Amount
$320,936.00
Summary
Thalassaemias are the most common hereditary diseases effecting the production of red blood cells. The underlying cause of disease is a failure to produce normal quantities of haemoglobin (Hb; the essential oxygen-carrying molecule in blood), resulting in severe anaemia. We have discovered a new protein with an important role in Hb production. We will elucidate the function of this protein in red blood cells and investigate novel treatments for thalssaemia disease.
The Implications Of Focal Adhesion Organization On Signal Transduction
Funder
National Health and Medical Research Council
Funding Amount
$565,614.00
Summary
The areas of a cell's attachment to their surroundings are known as focal adhesion. Apart from linking the inside and outside of a cell, focal adhesions act as a communication centre transmitting incoming and outgoing signals. How focal adhesions themselves are organized is currently not known. We propose to adhere cells to model surfaces to control the protein and membrane structure of focal adhesions and measure how focal adhesion structure affects cell communication.
Investigating The Role Of Novel Heterochromatin And Centromere Proteins In Chromosome Segregation
Funder
National Health and Medical Research Council
Funding Amount
$522,896.00
Summary
The equal division of genetic material during cell division is essential so that genetic material is not lost or gained. This process is controlled by a complex array of proteins that replicate the genome, maintain its structural integrity, and equally distribute one copy to each daughter cell. This research aims to study the functions of newly identified proteins required for this process in a single cell yeast model-system and in human and mouse cells.