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Automated screening of compounds libraries

Published on 5 August 2022
Collaborations and service activities
Leader Caroline Barette

The role of this activity is to allow academic laboratories access to the necessary tools to perform chemical genetics screens.

Chemogenetic approaches require several essential elements, all available at the CMBA: a collection of chemical compounds, an automated screening platform, miniaturised tests, and an information system allowing recording and analysis of data ("TAMIS" software). This screening activity is carried out in collaboration with the project leaders from academic laboratories. More rarely, this activity is also available to industrial laboratories. Almost 20 screening projects have been completed or are ongoing.

A screen can be summarised as follows:
• Analysis of the project and evaluation of its feasibility.
• Advice and assistance for miniaturisation.
• Access to the screening laboratory and apparatus for adaptation of the tests.
• Access to collections of chemical compounds, as part of inter-platforms agreements and links with compound library suppliers (when compound libraries are distributed through academic laboratories).
• Assistance in the choice of chemical collections to test, depending on the ultimate aim.
• Robot programming and optimisation of the test.
• Screening of all or part of the collections of chemical compounds in 96-well plates.
• Analysis and selection of hits.
• Hit-picking and validation screening.
• Transfer of results (minimally as raw data associated with the structures of the compounds from the compound library) both to the project leader (biologist) and to the chemists holding the compound libraries (only in the case of academic screens).

The search for commercially available structural analogues is carried out by external experts (chemists) and their synthesis can be carried out in collaboration with the CCHD (Saclay).

In parallel to its screening activity, the CMBA has developed the TAMIS software for the analysis and management of chemical and biological data. This software was developed with the software engineers at the CEA (EDyP and GIPSE) and is regularly implemented through the participation of the CMBA. In addition, the CMBA collaborates with Robert Nadon (Université McGill, Canada) for the development of a new statistical method for the analysis of automated screening data, in order to be able to detect weakly bioactive compounds.