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Analyse van serine proteasen en serine protease inhibitoren: evolutionaire en structurele inzichten

This work mainly deals with analyses of proteolytic enzymes, their sequence, structure and function. Serine proteases are an important class ofproteolytic enzymes and they play an important role in wide variety of pathways and they are inhibited by serpins (serine protease inhibitors).The evolution of serine proteases will be studied to prove that all theserine proteases have been evolved from a single gene by gene duplication. By comparative sequence analyses, new members would be identified inthe family of serine protease inhibitors, the neuroserpin and by comparative structural analyses, the unique structural patterns and the uniquestabilizing interactions of the neuroserpin family would be studied. The structural similarities between other classes of proteolytic enzymes such as, serine racemases and threonine deaminases would be studied to correlate functional similarities between the two enzymes. Protein-proteininteractions of a wide variety of protein complexes would be predicted using a statistical method called MAUT and the reliability of the methodwould be explained by predicting interface of a serine protease enzyme.Genomics of Daphnia Gene prioritization of immunity genes would be performed in Daphnia pulex using multi-objective genetic algorithms. So far,only 82 immune genes have been found using sequence-similarity measuresand phylo-genetic analysis. With the already known genes, the aim wouldbe to find new immune genes involved in Daphnia. Prioritization will bebased on data sources such as literature, Wfleabase database data (Daphnia genomics consortium), sequence similarity, EST and microarray data, gene location etc. Multi-objective genetic algorithms will then be used to obtain a pareto-surface (a set) of solutions, from which the user canselect the best solution, based on the priority given to a particular feature. This tool will be written using a combination of Java, shell script and perl and possibly other programming languages. The expected outcome will be a tool that can prioritize the genome and to find new genes that are involved in the immunity of Daphnia pulex. From the methodological point of view, this work would mainly focus on MAUT (Multi-AttributeUtility Theory) and MOGA (Multi-Objective Genetic Algorithms).
Datum:1 apr 2010  →  28 sep 2012
Project type:PhD project