This project has a double goal: to develop a descriptive analysis grid with all known mutations, and to develop a predictive tool to facilitate the understanding of human disease mutations. This project is part of the overall goal to understand the mechanisms controlling protein functions. Indeed, the way a protein folds determines its interactions with the cellular environment, including the way in which it interacts with therapeutic molecules.
Firstly, a relational database (MS2PH-db) was created. It contains the structural and evolutionary data, linked to the phenotypic and mutational data of 1036 proteins involved in human genetic diseases. This database is updated automatically.
A web server, MAGOS, was also developed. It enables scientists to perform an exhaustive research of the sequences/structures homologous to a particular protein involved in a human disease. It will be coupled with the automatic generation of a 3D model of the protein sequence, based on the closest known structure.

Members of the MS2PH team: from left to right: Olivier Poch, Anne Friedrich, Luc Moulinier, and Raphaël Bolze, at the "Institute of Genetics and Molecular and Cellular Biology (IGBMC) in Illkirch.
 
In 2005, Hoan Nguyen became a member of the Strasbourg team in order to develop a relational database able to integrate and interrogate all of the accumulated data.

To synthesize a protein, the gene (present in the DNA molecule) delivers into the cell, a production code in a process called splicing. During this step, the cell assembles end-to-end, elements from the original code - the exons. The same gene can therefore produce several generation codes. This process is called "alternative splicing", the process by which a single gene can produce several proteins.
This project proposes to analyse the links between splicing defects and genetic diseases.
The analysis of the mutations in the genes of individuals affected by genetic diseases and the splicing consequences should provide fundamental knowledge for the comprehension of these diseases. This study should enable scientists to develop therapies based on the splicing reparation, e.g. exon skipping.
The first part of the project consisted in establishing a database of the different splicing sites of human genes.

Some of the team members: from left to right: Yann Guermeur, Fabrice Leclerc, and Raphaël Bolze in the "Laboratoire Lorrain de Recherche en Informatique et ses Applications" (LORIA), in Nancy.
 
Raphaël Bolze, from the ENS Lyon, carries out the adaptation of the algorithm applications (gridification and portage) for both teams.