Unit: Macromolecular crystallisation and X-ray diffraction facility

Director: ALZARI, Pedro M.

The goal of the platform is to include all the equipment and technology required for crystallogenesis, computing and X ray diffraction that are required by the different research teams working on macromolecular crystallography at the Institut Pasteur, as well as to develop high-throughput methodologies for gene cloning, protein production and crystallization, by automating the different steps of the process.

Structural Genomics of Mycobacteria (P.M. Alzari, S.T. Cole, J.M. Betton, et al)

The availability of massive amounts of data from genomic projects is imposing a novel dynamics to structural biology, in particular promoting the introduction of high-throughput methodologies into the discipline. This is possible thanks to the remarkable technological advances in a number of disciplines such as gene cloning, protein expression and purification, structure determination methods, crystallogenesis, synchrotron radiation sources, computing science and cryocrystallography. We wish to use these technologies to contribute towards the development of a better chimiotherapy for tuberculosis. In particular, we propose a structural genomics approach as a tool for the discovery of novel drug targets in mycobacteria.

Supported by grants from the National Genopole Network, two European projects (X-TB and SPINE) and the Institut Pasteur, we have undertaken a structural genomics project on mycobacterial proteins, in collaboration with other laboratories within the Institute. The initial list of targets includes a number of proteins that are known to be important for mycobacterial survival and/or virulence, as well as many others of unknown biological function but whose relevance as potential therapeutic targets is highlighted by the comparative analysis of mycobacterial genomes (M. tuberculosis, M. leprae). The project is well underway: more than 300 mycobacterial genes have now been subcloned into bacterial expression vectors, several purified proteins have been subjected to crystallization trials and the first crystal structures have been determined during the last year. The up-to-date status of the project is described in the dedicated Web site "Structural Genomics of Mycobacteria" (http://www.pasteur.fr/SGM).

Keywords: structural genomics, gene cloning, protein purification, crystallogenesis, X-ray diffraction

Activity Reports 2003 - Institut Pasteur

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