Elucidating Mechanisms For The Biological Activities Of CD46.
Funder
National Health and Medical Research Council
Funding Amount
$228,000.00
Summary
The CD46 protein enables entry into cells of a number of different pathogens, including the measles virus, Neisseria meningitidis (the major cause of meningococcal disease), Neisseria gonorrhoea, Human Herpes Virus 6, and group A streptococcus. In addition, by binding to a key blood component that is often attached to foreign pathogens, CD46 can facilitate binding and entry of other pathogens. As well as facilitating entry of the pathogen, it has recently become apparent that CD46 binding trigge ....The CD46 protein enables entry into cells of a number of different pathogens, including the measles virus, Neisseria meningitidis (the major cause of meningococcal disease), Neisseria gonorrhoea, Human Herpes Virus 6, and group A streptococcus. In addition, by binding to a key blood component that is often attached to foreign pathogens, CD46 can facilitate binding and entry of other pathogens. As well as facilitating entry of the pathogen, it has recently become apparent that CD46 binding triggers a wide range of responses from the human host. Some of these responses are likely to further facilitate survival and proliferation of the pathogen, but others are more likely to facilitate host defence. For examples, signals triggered by binding to CD46 can both abrogate some aspects of the immune response (and it is though that this immunosuppression contributes to the secondary infections that cause the death of nearly one million children each year) and facilitate other aspects of the immune response. By understanding the mechanisms by which CD46 triggers these complex responses, we firstly be able to dissect how important each of these processes are to the overall pathogenecity of the virus or bacteria. Furthmore, this understanding will allow us to design better vaccines and drugs to combat these diseases.Read moreRead less
Assembly Of Mitochondrial Respiratory Chain Complexes And Defects Associated With Disease
Funder
National Health and Medical Research Council
Funding Amount
$464,610.00
Summary
A group of protein assemblies termed respiratory complexes are found in the inner membrane of mitochondria in our cells and are responsible for producing most of our energy. These complexes consist of many different protein subunits and are built by the help of numerous known and unknown assembly factors. For example, assembly of Complex I of the respiratory chain requires 39 different proteins that are made outside mitochondria and are then transported inside to be somehow joined together with ....A group of protein assemblies termed respiratory complexes are found in the inner membrane of mitochondria in our cells and are responsible for producing most of our energy. These complexes consist of many different protein subunits and are built by the help of numerous known and unknown assembly factors. For example, assembly of Complex I of the respiratory chain requires 39 different proteins that are made outside mitochondria and are then transported inside to be somehow joined together with the 7 other subunits that are made by mitochondria. This is clearly a complicated procedure and we have little information on how its assembly is achieved. We do know however that mistakes in the assembly of these complexes (particularly Complex I) do happen. In Australia, about 50 children born each year have inherited disorders of mitochondrial energy generation. The most severe disorders cause infant death, while others present later causing a range of degenerative diseases, particularly affecting brain, muscle and heart. Defects in the respiratory chain have also been implicated in Parkinson's disease, Alzheimer's disease, type-2 diabetes and in cell death. In order to understand how respiratory complex defects cause disease, we need to understand more about how these complexes are built. The aim of this proposal is to investigate how Complex I is assembled, how it interacts with other respiratory complexes, and to identify and characterise proteins that aid in its assembly. We will also analyse assembly defects in cells from patients with suspected respiratory complex deficiencies. This work will aid in our understanding of not only how protein complexes are built, but how defects in their assembly can cause disease. This will be informative to families of affected individuals and may aid in future diagnosis and prevention of diseases where defects in mitochondria are implicated.Read moreRead less