Netherlands Centre for Electron Nanoscopy

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New treatments against tuberculosis

The group of prof. Peter J. Peters (NKI-AVL) identified a pathogenic pathway of M. tuberculosis (Cell, 2007) and aims at using the cryo-TEMs for investigating this pathway at macromolecular level. They will use single particle analysis to study proteins of the bacteria type VII secretion systems (Nature Rev Microbiol, 2007), that are involved in the killing of human cells. Atomic structures will be ‘docked’ into the lower resolution particle density maps to create templates for a macromolecular atlas of the nano machinery in cells made by cryo-electron tomography.

Reconstruction of a protein used by Tubercle bacillus. From 2D tem images to a 3D reconstruction

Figure: substrate of a novel secretion nano-machine used by Tubercle bacillus to cause tuberculosis. The image shows a number of two dimensional particles randomly positioned; a three dimensional model of these particles resolved by single particle analysis at 9.4 Å resolution is depicted. (M. Sani et al. in prepation)

Publication:

van der Wel, N., D. Hava, D. Houben, D. Fluitsma, M. van Zon, J. Pierson, M. Brenner and P. J. Peters (2007). “M. tuberculosis and M. leprae Translocate from the Phagolysosome to the Cytosol in Myeloid Cells.” Cell 129(7): 1287-1298.

NeCEN is supported by:

Investing in your future Netherlands Organisation for Scientific Research Medical Delta - Health Science & Technology FEI Company - Tools for nanotech