About

The Technological Targeted Action Drug Discovery and Screening (ATC-DDS) coordinates projects and collaborations at the Institut Pasteur Paris campus on therapeutic development.

It raises awareness for DDS in basic research projects and stimulates intra-campus collaborations between Units, technological platforms and researchers with complementary expertise for innovative projects in the field of drug discovery. The ATC-DDS aims to strengthen collaborations within the Pasteur network and to increase national and international visibility in therapeutic development. It implements novel DDS technologies and anticipates potential future pandemics.

The ATC-DDS is led by Fabrice Agou, head of the Chemogenomic and Biological Screening Platform (PF-CCB) and Nienke Buddelmeijer, group leader of the Cell Shape and Pathogenicity group in the Biology and Genetics of the Bacterial Cell Wall Unit. They are advised by the ATC-DDS Scientific Advisory Board composed of Hélène Strick-Marchand, Nadia Naffakh, Iuliana Ene, Eric Prina, Ludovic Sauguet, Marcel Hollenstein, Olivier Sperandio and Christophe Zimmer. The SAB covers expertise in screening, in silico docking of molecules, adapted animal models to study human diseases, vaccine development strategies, structural biology and modeling, chemical approaches and artificial intelligence, on the scientific axes and concerted actions defined in the 2019-2023 strategic plan : Emerging Infectious Diseases, Antimicrobial Resistance, Brain Connectivity and Neurodegenerative Diseases, Cancer Initiative and Vaccinology and Immunotherapy initiative.

The PF-CCB platform has a large repertoire of state-of-the-art equipment to fulfill the needs of both phenotypic (High content screening HCS) and target-based (High-throughput screening HTS) screening projects on campus. To this aim, the platform has already developed biochemical, cellular and fluorescence microscopy screening tests and plans to extend its expertise in screening (i) by spatio-transcriptomic imaging on single cells, from organoids or patient tissues (Rebus Biosystems, Santa Clara, USA) and (ii) by high-throughput microfluidic interferometry (Creoptix, Switzerland).

Thanks to the ATC-DDS, the PF-CCB equipment was reinforced and the compound library collection at Institut Pasteur Paris is diverse and has been extended since 2021 with 7 new compound libraries, providing a total of 27 774 new compounds to the community. Four short-term research projects were financed under the ATC-DDS trainee call 2021 that all focused on the development or improvement of biological assays for future screening for antibacterial and antiviral molecules. Our IP expertise in DDS was shared both in France and in Europe through 7 yearly international lectures at Radboud University (Netherlands), and a yearly masterclass & accelerated learning series at Sup’Biotech (France) — all coordinated by Fabrice Agou and the PF-CCB. Finally, 2 full days DDS symposia and 2 seminars with international invited guests with expertise un the DDS field were organized on the campus for Pasteur researchers and external participants.

Teams

Equipment

The PF-CCB includes a number of equipements (more information) :

Echo Liquid Handler System – Labcyte – Echo 550

Octet Instrument – ForteBio – Octet HTX System

Wide field microscope – Olympus – IX83

High resolution microscope equipped with a numerical aperture optical system based on the structured illumination of light (synthetic aperture optics) – Rebus Biosystems – StellarVision

Plate reader for Dynamic Light Scattering (DLS) – Wyatt Technology – DynaPro Plate Reader II

Combination Washer Dispenser EL406 for 96/384/1536 -well microplates, equipped with a microplate stacker “Biostak 3” – Agilent BioTek

 

The concomittant actions of the ATC-DDS, the PF-CCB and its collaborators allowed the acquisition of 2 new equipments which will complete the technology park of the DDS on the Institut Pasteur campus :

For HTS : Grated-coupled interferometry (GCI) (Creoptix AG , WAVEcore), available at the PF-CCB by the first semester of 2023

For HCS : Rebus Esper (Rebus Biosystems) ; available for tests, planned purchase by 2023-2024 if positive feedbacks

 

 

Chemical Libraries available at Institut Pasteur

Thanks to the work of the Institut Pasteur (IP) chemistry research teams and the ATC-DDS and PF-CCB efforts to strengthen the IP chemical diversity, a wide and growing variety of chemical libraries are now available on the campus:

RNA-protein interaction inhibitors Library (2095 compounds, ChemDiv)

Small drug-derived metabolites Library (149 compounds, MedChemTronica)

FDA-approved & Passed Phase-I Drug Library (3256 compounds, L3800, Selleck Chemicals)

Antibacterial Screening Compounds Library (10 880 composés, Antibacterial, LifeChemicals)

         Antifungal Compound Library (253 compounds, L4500-UB100, TargetMol)

         Discovery Diversity Set (10 240 compounds, Enamine)

FDA-approved Compound Library (1262 compounds, 2018 LOPAC, Sigma)

FDA-approved Compound Library (1070 compounds, 2021, Home-made IP)

Anti-Cancer Compound Library (901 compounds, L3000, Selleck Chemicals), completed in 2022 with 2936 additional anti-cancer compounds thanks to Institut Pasteur Cancer Initiative

Nucleoside Analogue Library (134 compounds, L7200, Selleck Chemicals)

Higly Selective Inhibitor Library  (597 compounds, L3500, Selleck Chemicals)

Fragment Library (1014 compounds, L1600, Selleck Chemicals)

Ubiquitination Compound Library (198 compounds, L6000, Selleck Chemicals)

Compound Library for research on Ubiquitination (678 genes / 4 siRNA / 4 gRNA, Dharmacon)

Antiviral Library (105 compounds, Home-made IP)

3CLpro-Targeted Compound Library (162 compounds, L1712, TargetMol Chemicals)

Lipid Metabolism Compound Library (292 compounds, L2510, TargetMol Chemicals)

Natural Compound Library (480 composés, Green Pharma)

National Compounds Library / Chimiothèque Nationale (71744 compounds, ChemBio France)

Protein Kinases Inhibitors Library (10000 compounds, InhibKinase, ChemDiv)

Nucleoside Analogs Library (4620 compounds, NECAN, ChemDiv)

ATP Analogs Library (10000 compounds, Chem-X-infinity)

Protein-protein Interaction Inhibitors FrPPIChem Library (10 314 compounds, Home-made IP)

DARPin Library (N2C et N3C, > 1012 variants, Home-made IP)

Coiled-coil Peptides Library (> 1012 variants, Home-made IP)

Nucleosides and Epidrugs Library (318 compounds, Dr Paola Arimondo, Home-made IP)

Nucleoside Analogs Library (1360 compounds, Dr Sylvie Pochet, Home-made IP)

IPPA Library (1600 compounds, Dr. Yves Janin, Home-made IP)

Serine Proteases Inhibitors Library (50 compounds, Pr. Charazade El Amri, Sorbonne Université)

Teaching

  7 international Courses on  “Imaging in modern cell biology and drug screening” lectured by Fabrice Agou (Institut Pasteur) at  Radboud University (Netherlands)
–> Annual 6-weeks Teaching cycle, starting Spring 2023

         Masterclass / Sup’Biotech Accelerated Learning Series on “Advanced Techniques for Drug Discovery: From Screening Strategies to Preclinical Animal Testing (models)” by the PF-CCB Team members at Sup’Biotech (June 2023) :

        • “Screening strategies and technologies” (J. Chiaravalli – PF-CCB)
        • “Biophysical methods for hit validation” (O. Reznichenko – PF-CCB)
        • “ADME studies in early drug discovery” (F. Leroux)
        • “Accelerating the development of new drugs – infrastructures and services to implement in vivo studies from maximal tolerated dose to efficacy testing” (M. Bérard)
        • “Development of preclinical animal models” (E. Giraud – PF-CCB)

 

–> Full program of the Masterclass

Animation and Support

The coordinators of the ATC – Drug Discovery & Screening are supported by Mallory Perrin-Wolff and Emilie Boutet (Scientific Programming and Incentive Actions Department – SPAIS) for the organization of different actions: communication, workshops, incentive actions, training, etc…

Emilie Boutet
Project Manager
Mallory Perrin-Wolff
Head of Structure