Integration of enhanced protein function prediction with experimental studies of fertilisation in Plasmodium - a wet/dry study

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This proposal is to conduct a wet/dry study that will benefit from the synergies of a computational group developing novel bioinformatics strategies for protein function prediction working closely with an experimental group requiring these methodologies to prioritise wet studies to extend our understanding of fertilisation in Plasmodium. Genome projects are determining the sequences of proteins in numerous species including, man, model mammals, plants (including those of relevance to agriculture), and pathogens of human, animals and plants. Central to the understanding and exploitation of this information is the assignment of function to the proteins. A range of computational approaches have been developed to assign function to proteins. Several approaches, including one developed in our group, use information from the sequence and the 3D protein structure. Other approaches use information at a systems level / which genes are turned on or off together (transcriptomics, proteomic) and which proteins interact (interactomic). This proposal is to develop an enhanced method of function prediction that integrates information from sequences, structures, transcriptomes , proteomes and interactomes. The computer program will be made available to the academic community via a web server. We will also take part in international blind trials of function prediction. This general development of software will be targeted at understanding the fertilisation of Plasmodium gametes. One particular species of Plasmodium, (Plasmodium falciparum) is the parasite that is responsible for the majority of malarial deaths. The disease presents a risk to 40% of the world's population and is responsible for c. 400 million cases and 3 million deaths annually world wide. Plasmodium is transmitted from person to person by the bite of an anopheline mosquito. In addition, Plasmodium, and notably Plasmodium berghei (a parasite of rodents, that is not pathogenic to man) has become a model organism for study of parasite/host interactions because of the importance of understanding the molecular basis of malaria. The proteins in the gamete of P. berghei have been recently characterised in our laboratory. To direct our proposed experimental studies, the enhanced bioinformatics tools for function prediction will be applied to these gamete proteins. In addition, the bioinformatics tools will be used to improve the functional annotation of Plasmodium sequences. Our results will be added to the community databases (Gene DB and PlamoDB) describing the annotation of Plasmodium.