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

这项建议是进行湿/干研究，将受益于一个计算组的协同作用，开发新的生物信息学策略，蛋白质功能预测与实验组密切合作，需要这些方法，优先考虑湿研究，以扩大我们对疟原虫受精的理解。基因组计划正在确定许多物种中的蛋白质序列，包括人、模式哺乳动物、植物（包括与农业有关的那些）以及人类、动物和植物的病原体。理解和利用这些信息的核心是蛋白质的功能分配。已经开发了一系列计算方法来分配蛋白质的功能。包括我们小组开发的一种方法在内的几种方法使用了来自序列和3D蛋白质结构的信息。其他方法使用系统水平的信息/哪些基因一起打开或关闭（转录组学，蛋白质组学）以及哪些蛋白质相互作用（interactomic）。本研究旨在发展一种整合序列、结构、转录组、蛋白质组和相互作用组信息的功能预测方法。计算机程序将通过网络服务器提供给学术界。我们还将参加国际功能预测盲法试验。这一软件的总体开发将以了解疟原虫配子的受精为目标。一种特殊的疟原虫（恶性疟原虫）是造成大多数疟疾死亡的寄生虫。这种疾病对世界40%的人口构成威胁，并导致C。全世界每年有4亿病例和300万死亡。疟原虫通过按蚊的叮咬在人与人之间传播。此外，疟原虫，特别是伯氏疟原虫（啮齿动物的寄生虫，对人不致病）已成为研究寄生虫/宿主相互作用的模式生物，因为了解疟疾的分子基础的重要性。最近在我们的实验室中已经表征了伯氏疟原虫配子中的蛋白质。为了指导我们提出的实验研究，增强的生物信息学工具的功能预测将适用于这些配子蛋白。此外，生物信息学工具将用于改进疟原虫序列的功能注释。我们的结果将被添加到社区数据库（基因DB和PlamoDB）描述疟原虫的注释。

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.