Investigating The Biological Significance Of Proteolytic Prion Protein Processing.
Funder
National Health and Medical Research Council
Funding Amount
$328,558.00
Summary
Prion diseases, including Bovine Spongiform encephalopathy (“mad cow disease”) and Creutzfeldt-Jakob Disease in humans are transmissible and fatal diseases that occur when the normal prion protein (PrPc) mis-folds and accumulates in the brain. The specific function of PrPc within a cell remains unclear, however its presence is essential for prion diseases to occur. This project aims to define how PrPc cleavage affects its biological function(s), and influences susceptibility to prion infection.
Haemolysins And Haemoglobinases As Anti-hookworm Vaccines.
Funder
National Health and Medical Research Council
Funding Amount
$322,951.00
Summary
To meet its growth and reproductive requirements, hookworms must be able to utilise host haemoglobin located in the red blood cells. To puncture the red blood cell membrane, and break down the exposed haemoglobin into small peptides or single amino acids; the hookworm uses proteases called haemolysins and haemoglobinases. Identifying these proteases and disrupting their function may lead to reduced worm burdens, size and fecundity. Therefore these proteases could be ideal vaccine candidates.
TRF2 Protein And T-loop Replication In Alternative Lengthening Of Telomeres
Funder
National Health and Medical Research Council
Funding Amount
$398,156.00
Summary
Telomere loss acts as a clock telling cells when to stop proliferating. Cancer cells ignore this clock and grow indefinitely by preventing the normal loss of telomeres. Little is known about one of the methods cancers use to preserve telomeres, called ALT, which is employed by some brain tumours and other cancers. We will determine if the TRF2 protein is involved in controlling ALT. This will lay the basis for future anti-cancer treatments targeted at ALT.
The Role Of Huntingtin Misfolding And Oligomerization In Huntingtons Disease
Funder
National Health and Medical Research Council
Funding Amount
$474,329.00
Summary
Mutations in the huntingtin gene cause Huntington's disease by making the gene product aggregate together into non-normal and different sized polymers. However, it is not understood how this process causes cells to die, largely because we don't understand how the abnormal forms accumulate in cells over time. We will examine where in cells the abnormal shapes accumulate and how they cause toxicity. This research will identify critically-needed therapeutic targets against Huntington's disease.
DNA-binding proteins regulate gene expression and co-ordinate normal patterns of development. We are investigating a set of DNA-binding proteins, termed the Ikaros family. These proteins are known to be important regulators of white blood cell production and mutations that interfere with Ikaros activity are associated with aggressive childhood leukaemias that are resistant to treatment. Recently, it has become apparent that Ikaros proteins also regulate genes in red blood cells. One observation ....DNA-binding proteins regulate gene expression and co-ordinate normal patterns of development. We are investigating a set of DNA-binding proteins, termed the Ikaros family. These proteins are known to be important regulators of white blood cell production and mutations that interfere with Ikaros activity are associated with aggressive childhood leukaemias that are resistant to treatment. Recently, it has become apparent that Ikaros proteins also regulate genes in red blood cells. One observation is that Ikaros plays a role in silencing the foetal haemoglobin genes. The haemoglobin genes have been extensively studied because diseases, such as beta-thalassaemia, which are caused by mutations in the adult haemoglobin genes, are among the most common genetic diseases known. One strategy to alleviate beta-thalassaemia centres around re-activating the foetal globin genes and thereby re-supplying globin to adults who have only mutant forms. In this context, the observation that Ikaros plays a role in foetal globin silencing is of considerable medical significance. We have recently identified two new regulatory proteins that are related to Ikaros and are found in red blood cells. Little is known about these proteins but they can directly bind to Ikaros and they are capable of silencing gene expression. We therefore wish to test the hypothesis that they work together with Ikaros to silence gene expression. Ultimately we expect that understanding how these proteins and Ikaros operate will suggest new strategies for re-activating the silent foetal globin genes to treat beta-thalassaemia, as well as preventing the proliferation of white blood cells carrying mutant Ikaros proteins.Read moreRead less