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High-Throughput screening facility - PARi

Plateformes
Published on 27 April 2022


The PARi facility, located at the Institute of Cellular and Molecular Radiobiology (CEA), is a technology platform dedicated to High-Throughput and High-content Screenings (HTS & HCS) performed on cell-based assays.

Our team has the expertise and the infrastructure to setup miniaturized and automated cell-based assays, to screen libraries of biological effectors in a systematic and massively parallel fashion, to quantitate single or multiplexed reporter assays and to perform statistical analyses of large datasets (Fig. 1).


   Guillaume PINNA
   Principal investigator​
   Phone: +33 (0)1 46 54 87 90
   guillaume.pinna@cea.fr

   Secretariat:
   Aurélie GOURET
   Phone: +33 (0)1 46 54 98 66

   Arielle LELIARD
   Phone: +33 (0)1 46 54 99 49

Image1.jpg
Figure 1: Areas of expertise of the PARi facility
 
In addition to its screening activities, our platform also offers access to its robotic and imaging infrastructure for routine cellular characterizations.



Technical offer

High-Throughput and High-content Screenings

All our screenings are conducted on mammalian cell-based assays, devised to report single or multiple biological functions. Additionally, some of our effector libraries (e.g. siRNAs, miRNAs...) require, by design, to work on human cells. In most cases, we rely on High content imaging for cell-based assay quantitation (Fig. 2).

Image2.jpg

Figure 2: High-Content Imaging (HCI). HCI couples automated fluorescence microscopy (allowing the acquisition of cellular images in microplates, typically in 96- or 384- well format) with image segmentation and analysis software. This approach allows the direct and simultaneous analysis of multiple cellular features (size, morphology, localization or intensity of fluorescence...), and establish a phenotypic profiling in response to a cellular perturbation. HCI used in the context of a screen is called High Content Screening (HCS).
 
Our facility works in close collaboration with the other iRCM platforms to propose a complete experimental solution for our screening projects (e.g. Cigex platform for the establishment of transgenic cell lines, cytometry platform for cell isolation or enrichment, irradiation platform for projects with a radiobiological component, imaging platform for the in-depth characterization of cellular assays, etc…). Our team adopts a quality approach to ensure traceability and confidentiality of results throughout a screening project.
 
Based on these fundamentals, we are able to propose multiple screening strategies:
 
  • Functional genomics by gene loss-of-function screens (siRNA library screening).
  •  Functional miRNomics by loss- or gain-of-function of microRNAs (screening of miRNA antisense or mimics libraries).
  •  Small molecule libraries screening.
  •  Custom screening solutions: combinatorial, modifier, differential screens, miRNA target identification by STaRs Assay (see FAQ), other custom screens...
All these screening approaches aim at cataloguing candidate drugs, genes or miRNAs playing a role in a biological function or a metabolic pathway of interest.These candidates can then serve as springboards for the development of new exploratory strategies, with fundamental or therapeutic aims.



Routine services

 
Our facility also offers various routine services:
 
  • Setup and optimization of miniaturized cell-based assays (96- and 384-well format).
  • Automation of cell handling (e.g. cell seeding, transfections, standardized dose-responses, reporter assays...). 
  • Image acquisitions and quantitation, phenotypic profiling.
  •  Data processing and statistical analysis of large-scale datasets.