Metabolomic Analysis And Membrane Transport Proteins In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$368,875.00
Summary
The malaria parasite is a single celled organism which invades the red blood cells of those it infects. There is no vaccine and the parasite is becoming increasingly resistant to the drugs that we have available. There is therefore an urgent need for new antimalarial strategies. Research in this area has been helped by the sequencing of the genome of the parasite. However we still don t know what most of the genes in the parasite do, and it is not a straightforward matter to find out. One of the ....The malaria parasite is a single celled organism which invades the red blood cells of those it infects. There is no vaccine and the parasite is becoming increasingly resistant to the drugs that we have available. There is therefore an urgent need for new antimalarial strategies. Research in this area has been helped by the sequencing of the genome of the parasite. However we still don t know what most of the genes in the parasite do, and it is not a straightforward matter to find out. One of the things hampering us in our efforts to develop new antimalarial drugs is our relatively poor understanding of the sorts of biochemical pathways that the parasite relies on to support its high rate of growth and replication inside the red blood cell, as well the biochemical mechanisms that enable it to becomes drug-resistant. In this study we will use a range of modern analytical techniques to carry out the first detailed survey of the biochemical composition - the so-called metabolome - of the parasite. We will investigate how this changes in response to nutrient deprivation, in response to mutations in genes which play a key role in antimalarial drug resistance and in response to changes in the expression of genes encoding proteins which we believe to be involved in the uptake of nutrients by the parasite. This project will provide us with a wealth of new information about the biochemical make-up of the parasite, and it will provide new insights into the biochemical pathways that are operating and which might be targeted with new drugs. The work is likely to provide new insights into mechanisms of antimalarial drug resistance. It will also form the basis for a strategy that is likely to be extremely useful in helping us to ascribe function to the many genes involved in the biochemistry of this important human pathogen.Read moreRead less
Examining The Role Of Profilin As A Regulator Of Cancer Aggressiveness
Funder
National Health and Medical Research Council
Funding Amount
$261,778.00
Summary
Cancer treatment in Australia costs ~ $2.7 billion per annum. Current mainstream treatments often cause major side effects and thus less toxic therapeutic approaches are urgently needed. Profilin has recently emerged as a promising anti-cancer target. We will investigate how cancer can be suppressed by altering the interaction between profilin and its partners (lipids, phosphoinositides, and actin). This project will provide essential groundwork for the development of novel cancer therapeutics.
Our current understanding of cellular signalling and disease is based on ensemble measurements over a cellular or molecular population. While these measurements have provided valuable information on the molecular circuitry required for cellular function, there is a lack of detail on the spatio-temporal dynamics of signal initiation and propagation at the single molecule and single cellular level. Single particle (molecule or cell) approaches offer the advantage of being able to detect individual ....Our current understanding of cellular signalling and disease is based on ensemble measurements over a cellular or molecular population. While these measurements have provided valuable information on the molecular circuitry required for cellular function, there is a lack of detail on the spatio-temporal dynamics of signal initiation and propagation at the single molecule and single cellular level. Single particle (molecule or cell) approaches offer the advantage of being able to detect individual processes including rare events that would be lost in an ensemble measurement. Moreover single particle approaches provide dynamic-kinetic information that does not rely on synchronising a population of molecules or cells. In this proposal we aim to build on our combined expertise in EGF-EGFR signalling, biophysics, biosensors, quantum dot nanotechnology and single molecule spectroscopy to learn more about how EGFR cellular signalling works and how it is impaired in cancer. This project will provide basic information that could lead to the design of more effective drugs directed agaisnt this therapeutic target.Read moreRead less