Final Activity Report Summary - MALARIA SURFEOMICS (Plasmodium falciparum malaria: exploring sub-telomeric genes with the novel proteomics method "surfeomics")
This project was designed to examine the relationship between certain proteins in the malaria parasite and the severity of the accompanying disease. Following infection with the parasite, certain proteins are made by the parasite to defend itself against the host's immune system. These proteins consist of a large family of structurally different proteins with similar properties. The variability in the protein structure helps the parasite avoid the immune system as the host generally has a limited repertoire of antibodies. It has been hypothesised that the specific protein made at any given interval will correlate with the severity of the malaria infection. In other words, certain protein structures associate with the level of disease.
In order to explore this point, we examined proteins in the malaria parasite Plasmodium falciparum. The initial samples were obtained from children in Uganda who had been diagnosed with malaria - both mild and severe. We selected 93 children for inclusion in this study. We identified thousands of different proteins found in the malaria parasites from these children and attempted to correlate protein structure with the level of disease. Due to the large amount of data collected, it was necessary to develop custom computational (bioinformatics) methods to analyse the data. Using these specialised bioinformatics methods, we were able to identify specific structural regions of the protein that were associated with disease severity. These results could be useful for the development of a vaccine for malaria, because they provide information on which protein structures are important.
The next portion of the project involved developing a specialised database for all of the proteins analysed in the first portion of the project. This database contains all of the different proteins identified in the first phase of the project as well as thousands of other proteins taken from literature sources. We then further expanded this project beyond malaria to include proteins from other pathogens. Once all of these data were collected, we entered them into the database. This data is publicly available and can be viewed at http://www.vardb.org(odnośnik otworzy się w nowym oknie). In order to analyse these thousands of proteins, we developed a number of different custom bioinformatics tools. These tools have also been made freely available on the homepage of the database. This resource should be useful for comparing different mechanisms of disease across many different species. It is likely that mechanisms used in one species involving one specific set of proteins can be employed by other pathogens. Accordingly, results obtained for one disease can potentially be applied to many other diseases. It is therefore intended that this database serve as a resource and central repository for protein information from many different diseases. This information will hopefully be useful for the development of new vaccines and novel medicines.
In order to explore this point, we examined proteins in the malaria parasite Plasmodium falciparum. The initial samples were obtained from children in Uganda who had been diagnosed with malaria - both mild and severe. We selected 93 children for inclusion in this study. We identified thousands of different proteins found in the malaria parasites from these children and attempted to correlate protein structure with the level of disease. Due to the large amount of data collected, it was necessary to develop custom computational (bioinformatics) methods to analyse the data. Using these specialised bioinformatics methods, we were able to identify specific structural regions of the protein that were associated with disease severity. These results could be useful for the development of a vaccine for malaria, because they provide information on which protein structures are important.
The next portion of the project involved developing a specialised database for all of the proteins analysed in the first portion of the project. This database contains all of the different proteins identified in the first phase of the project as well as thousands of other proteins taken from literature sources. We then further expanded this project beyond malaria to include proteins from other pathogens. Once all of these data were collected, we entered them into the database. This data is publicly available and can be viewed at http://www.vardb.org(odnośnik otworzy się w nowym oknie). In order to analyse these thousands of proteins, we developed a number of different custom bioinformatics tools. These tools have also been made freely available on the homepage of the database. This resource should be useful for comparing different mechanisms of disease across many different species. It is likely that mechanisms used in one species involving one specific set of proteins can be employed by other pathogens. Accordingly, results obtained for one disease can potentially be applied to many other diseases. It is therefore intended that this database serve as a resource and central repository for protein information from many different diseases. This information will hopefully be useful for the development of new vaccines and novel medicines.