Nuclear Retention-and-release Of RNA: A Naturally-occurring Mechanism For Controlling Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$428,753.00
Summary
The deliberate retention of messenger RNA in the nucleus is a newly-discovered biological mechanism used by cells to control which genes are made into proteins, and when. This is a fundamental process in health and disease. The project will employ cutting edge molecular and cellular techniques to discover the principles underpinning nuclear retention. These insights will allow the development of new methods to spatially and temporally control gene expression in diverse gene therapy applications.
Malaria is a very important disease worldwide, causing hundreds of millions of cases and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by red blood cells which contain malaria parasites sticking to the lining of microscopic veins and clogging them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by ....Malaria is a very important disease worldwide, causing hundreds of millions of cases and about two million deaths per year. Severe malaria including cerebral malaria is a major cause of death. It is caused by red blood cells which contain malaria parasites sticking to the lining of microscopic veins and clogging them; what happens after this is complex. The process of sticking is called cytoadherence. We have discovered a gene which is important in this process of sticking. We have called it by the acronym clag, for cytoadherence-linked asexual gene; most Australians know of Clag as a glue. Our evidence for this has been accepted for publication by the prestigious USA journal Proceedings of the National Academy of Sciences of the USA. Recent work overseas aimed at determining the entire DNA sequence of the malaria parasite has shown that clag is not alone; there are at least 9 slightly different clag genes in the malaria parasite. What do the others do? We propose two possibilities. The first is that all of them act in cytoadherence but that different clags enable the parasitised cells to stick to different things on the lining of veins. The second is that they enable the parasitised cells, or perhaps the parasites alone, to stick to other things at different stages of the complex life cycle of the parasite. The experiments that we propose should show whether either of these proposals is true.Read moreRead less
Modulation Of Gene Regulation By DBHS Protein Interactions
Funder
National Health and Medical Research Council
Funding Amount
$443,244.00
Summary
The DBHS family of proteins have been shown to affect, in a novel manner, the way human cells control which genes are made into proteins - a fundamental process in healthy and cancerous cells. This project will employ cutting edge structural, molecular and cellular techniques to determine how these protein molecules interact with each other and with important gene regulatory proteins to determine cell fate.
I am a neuroscientist working on determining the different pathogenic mechanisms occurring in neurodegenerative movement disorders and dementias, and translating these findings for clinical neurologists and neuropathologists.
The cell is the building block of life. This proposal focusses on the surface of the cell, the plasma membrane, and specialised structures called caveolae that are an abundant feature of animal cells. Altered caveolae are a feature of many human disease conditions. In this proposal we will address the function of caveolae. We will test the idea that proteins are released from caveolae into the cell when cells are stressed forming a novel signalling pathway disrupted in disease.
Defining The Role Of A Palmitoylated Variant Of Sphingosine Kinase 1 In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$603,452.00
Summary
Sphingosine kinase is a protein that when dysregulated is involved in cancer development and progression. We have recently made a substantial breakthrough in this area by identifing a naturally occuring variant of sphingosine kinase that is constantly activated and has an enhanced ability to induce cancer. In this study we will examine and target this form of sphingosine kinase as a potential therapeutic intervention in cancer.