Structural Imaging Facility #F2
To place the Human Technopole (HT) at the forefront of innovation in biomedical research, a state-of-the-art cryo-EM infrastructure is needed. Indeed, the past two years have seen a revolution in structural biology. Single-particle cryo-electron microscopy (cryo-EM) was once limited to determining structures at resolutions so low that chemical features could not be distinguished. But with the advent of direct-electron detectors, single-particle cryo-EM has begun to achieve atomic resolutions that were previously available through crystallography only. At these resolutions, chemistry can be related to both structure and sequence.
Importantly, cryo-EM does not require crystal formation and needs only minuscule amounts of homogeneous sample. In principle, any biological problem can be tackled, with sample preparation (i.e. biochemistry) being the primary (if not only) limiting factor. This technique is thus mandatory for a comprehensive approach to Precision Medicine. The genome sequencing of each individual patient will provide us with information on the mutations underlying genetic diseases or cancer. Meanwhile, structural proteomics can provide additional information, namely: (i) Why does the mutation cause the disease? (ii) How can new drugs be designed for currently untreatable diseases? (iii) What existing drugs might be useful for known diseases? (iv) How can existing drugs be optimized to increase their power?
The Structure Imaging Facility will comprise laboratories for Electron Diffraction Tomography and Electron Cryo-Tomography.
The F2 will act as a Structural Biology hub: molecular targets will be identified by the sequencing facility within the context of the activities of the Oncologic, Neurosciences and Nutrition Genomics Centers. These targets will then be sent to the Electron Microscopy Facility for structural characterization. This workflow will be of paramount importance in exploiting protein targets for drug design and in characterizing the molecular mechanisms of oncological and neurodegenerative disorders. The Structural Imaging Facility will collaborate closely with the Big Data and Biocomputing Center. This is crucial, as the Facility will easily produce more than one Terabyte of data per day, creating a data analysis challenge that can only be addressed by HT multicentric structure.
New experimental method of advanced 3D Electron Diffraction data collection developed for transmission electron microscopes.
Advanced imaging technique used to produce high-resolution (~4 nm) three-dimensional views of samples, typically biological macromolecules and cells.
This infrastructure will be positioned within HT and act as a Structural biology hub for the Oncologic, Neurosciences and Nutrition Genomics centers as well as for external laboratories. The F2 will closely collaborate with Big Data and Biocomputing centers to manage the daily production of more than 1 Terabyte of data. The facility will also actively promote the participation in European and global initiatives (Instruct, Inext) in order to act within a broader international context.