Our Research Projects

Exploring the frontiers of computational biology and molecular modeling

Active Projects

P2X7

Active 2019

Elucidation of the mechanism of action of the homotrimeric channel receptor P2X7 and identification of novel positive and negative allosteric modulators

Coordinator:

Nicolas RENAULT, PhD

Team Members:

Corentin BEDART, PhD, PharmD, Amaury FARCE, PhD, Tanguy VILLEVAL

Funding:

CPER Resistomics

P2X7

Active 2019

Description

P2X7 is a homotrimeric channel receptor whose activation by extracellular ATP allows calcium influx and sodium efflux across the membrane. This receptor is involved in inflammation as its activation by an orthosteric agonist triggers the activation of the NLRP3 inflammasome and the release of pro-inflammatory cytokines IL-1β and IL-18. By adding certain positive allosteric modulators to the agonist, P2X7 can have an effect on the release of pro-inflammatory cytokines, helping to limit fibrosis and stimulate antitumor immunity. In terms of conformation, the binding of ATP to P2X7 causes a transition from the resting (closed) state to an open state. If this binding is prolonged, a new state appears, known as the macropore. This state allows molecules up to 900 Da to pass through. However, the molecular mechanisms governing the transition between the open state and the macropore state remain unknown. To try to address this issue, we used molecular dynamics to observe the stabilization of the receptor in its closed state or in these two other expected states. Elucidating this opening mechanism could pave the way for precision pharmacology. On the one hand, the development of positive allosteric modulators promoting macroporous opening in order to observe anti-fibrotic effects or to strengthen anti-tumor immunity. On the other hand, the development of negative allosteric modulators to stabilize the receptor in its closed state and observe anti-inflammatory effects.

Coordinator

Nicolas RENAULT, PhD

Team Members

Corentin BEDART, PhD, PharmD - Associate Professor
Amaury FARCE, PhD - Associate Professor
Tanguy VILLEVAL - PhD Student

Funding Sources

CPER Resistomics

Regional Ongoing 2021 - Present

Organization: CPER Resistomics

GPR35

Active 2026

Elucidation of the atomic-level pharmacology of GPR35 and identification of new, highly selective agonists, ideally possessing a biased signaling profile toward different biological response cascades.

Principal Investigator:

Corentin BEDART, PhD, PharmD

Team Members:

Amaury FARCE, PhD, Nicolas RENAULT, PhD, Tanguy VILLEVAL

GPR35

Active 2026

Description

Principal Investigator

Corentin BEDART, PhD, PharmD

Team Members

Amaury FARCE, PhD - Associate Professor
Nicolas RENAULT, PhD - Research Engineer
Tanguy VILLEVAL - PhD Student

ANDROMEDA

Active 2025

ANDROMEDA : a drug discovery library software that unifies laboratory data with computational drug discovery

Principal Investigator:

Corentin BEDART, PhD, PharmD

ANDROMEDA

Active 2025

Description

In the context of early drug discovery research, effective cooperation among all the key actors – namely chemists, biologists, and in silico researchers – is crucial. However, information sharing can rapidly become challenging due to the utilization of diverse tools and media by each discipline for the storage and exchange of its primary scientific outcomes. Certain tools are specifically designed for data sharing, such as chemical library software or research suites, including the free software L-g-chimio(1), TAMIS(2), or the commercial software Revvity Signals(3). Nevertheless, their usage remains constrained due to inherent limitations that restrict the capacity of specific disciplines to share their research data, offer sufficient ease of use within an entire laboratory, or in some cases, the financial burden that is difficult to assume at the academic level. To address these challenges, we introduce ANDROMEDA, a drug discovery library software that unifies laboratory data with computational drug discovery. Developed in Python using Django(4), PostgreSQL with the RDKit cartridge(5), and NGINX, ANDROMEDA provides a secure, local web application requiring no installation. Its intuitive interface ensures accessibility across disciplines, while Python integration enables seamless use of RDKit(5) and AI-driven prediction tools for ADMET parameters and pharmacological targets. ANDROMEDA centralizes synthesis/vendor data, biological assays, and storage information. Access is secured via IP whitelisting and user authentication, with granular permissions controlling project visibility and patentable structures. The main page displays compounds in a searchable grid, filterable by project, name, substructure, or similarity. Detailed compound pages include 1D/2D structures, physicochemical properties and structural alerts, synthesis batch data, biological activity, and supplementary files. The ANDROMEDA software solution remains in active development. If you are interested, feel free to try our demo and ask us to participate in the closed beta version.

Principal Investigator

Corentin BEDART, PhD, PharmD

Transcriptomic analysis of bulk and single cell RNA sequencing

Active 2023

Support for the analysis of INFINITE transcriptomic data obtained by bulk and single-cell RNA-Seq.

Principal Investigator:

Corentin BEDART, PhD, PharmD

Team Members:

Nicolas RENAULT, PhD

Transcriptomic analysis of bulk and single cell RNA sequencing

Active 2023

Description

Support for the analysis of INFINITE transcriptomic data obtained by bulk and single-cell RNA-Seq. - Identification of early genes in the pathophysiology of fibrotic interstitial lung disease in a new model of pulmonary fibrosis, in collaboration with Dr. DESSEYN Jean-Luc and HENNION Nathan - Evaluation of fibroblast and immune cells homogeneity and role in IBD, SS, HA and HC by single cell RNA sequencing, funded by the Fondation pour la Recherche Médicale (FRM)

Principal Investigator

Corentin BEDART, PhD, PharmD

Team Members

Nicolas RENAULT, PhD - Research Engineer

ACSL4

Active 2022

In silico study of Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) for the identification of potent inhibitors with antiferroptotic properties, in collaboration with Dr. EL BAKALI Jamal & Dr. RAVEZ Séverine, from LilNCog, Inserm U1172, Lille

Principal Investigator:

Nicolas RENAULT, PhD

ACSL4

Active 2022

Description

Principal Investigator

Nicolas RENAULT, PhD

Digestive mucins

Active 2022

Study of digestive mucins Muc5b and Muc5ac, in collaboration with Dr. Jean-Luc DESSEYN, INFINITE

Principal Investigator:

Nicolas RENAULT, PhD

Team Members:

Corentin BEDART, PhD, PharmD, Tanguy VILLEVAL

Digestive mucins

Active 2022

Description

Study of digestive mucins Muc5b and Muc5ac, in collaboration with Dr. Jean-Luc DESSEYN, INFINITE

Principal Investigator

Nicolas RENAULT, PhD

Team Members

Corentin BEDART, PhD, PharmD - Associate Professor
Tanguy VILLEVAL - Lpro student

FFAR4 (GPR120)

Active 2021

Leveraged homology modeling and molecular dynamics to map the structural activation of FFAR4 (GPR120), identifying novel pharmacophore constraints for the next generation of anti-obesity therapeutics.

Principal Investigator:

Amaury FARCE, PhD

Team Members:

Corentin BEDART, PhD, PharmD, Nicolas RENAULT, PhD, Guillaume PATIENT

FFAR4 (GPR120)

Active 2021

Description

G protein-coupled receptors (GPCRs) are important drug targets, accounting for 35% of all approved drug targets. These receptors are transmembrane proteins involved in cell signaling of external stimuli (hormones, neurotransmitters, ions...) and induce activation of the associated G protein via GDP/GTP exchange. Over the last 20 years, deorphanized GPCRs have been shown to be active in lipid metabolism: studies have shown that modulating the activity of GPR 120 (FFA4), mainly expressed in the tongue and intestine, has an impact on lipid intake (feeding) and absorption in mice, representing a new approach to promoting treatments for the prevention of obesity and cardiovascular disease. In addition to classical pharmaceutical chemistry studies, in collaboration with Prof. Naim Khan's team at the University of Burgundy, in silico methods were applied to study the structural characteristics of the protein.The lack of structural information on FFA4 and limited drug testing contribute to the application of in silico methods to determine the structural features and dynamic interactions of the protein. Homology modeling of different FFA4 states (inactive, intermediate and active) was carried out, and the associated G protein was modeled for the receptor's active state. Dynamic studies of the receptor in the membrane were used to refine the transmembrane (TM) helix domain. Identification of the active site and ligand interactions enabled preliminary docking studies of TUG-891, a potent selective FFA4 agonist, and revealed ionic interactions with positively charged residues in the binding pocket. Experimental cryo-EM structures were published during our in silico studies. While the experimental structures confirmed the structural properties of FFA4 observed in our homology model, further information on ligand binding can be derived from our model for FFA4 activation. Docking studies of 4 agonist ligands (TUG-891, oleic acid, linoleic acid and linolenic acid) were carried out and the results refined using molecular dynamics with the AMBER 14IPQ force field to take account of ionic interactions between the positively charged residues in the binding pocket and the carboxylic acid group of the ligands. Molecular dynamics experiments for the different protein-ligand systems identified the most stable binding mode, and enabled us to determine pharmacophore constraints for high-throughput virtual screening. The most promising compounds have been selected for biological testing.

Principal Investigator

Amaury FARCE, PhD

Team Members

Corentin BEDART, PhD, PharmD - Associate Professor
Nicolas RENAULT, PhD - Research Engineer
Guillaume PATIENT - PhD Student

Nuclear receptors

Active 2020

Study of nuclear receptors involved in inflammatory diseases, including PPAR, glucocorticoid receptor, steroid receptors, etc.

Principal Investigator:

Amaury FARCE, PhD

Nuclear receptors

Active 2020

Description

Study of nuclear receptors involved in inflammatory diseases, including PPAR, glucocorticoid receptor, steroid receptors, etc.

Principal Investigator

Amaury FARCE, PhD

PPM6

Active 2026

Study of a phosphatase essential for the Plasmodium replication cycle, PPM6, in collaboration with Pr ALIOUAT El Moukhtar from Institut Pasteur, Lille

Principal Investigator:

Amaury FARCE, PhD

PPM6

Active 2026

Description

Study of a phosphatase essential for the Plasmodium replication cycle, PPM6, in collaboration with Pr ALIOUAT El Moukhtar from Institut Pasteur, Lille

Principal Investigator

Amaury FARCE, PhD

Toxoplasmosis

Active 2022

Study of toxic compounds for the cystic form of Toxoplasma gondii, and identification of the molecular target, in collaboration with Dr GISSOT Mathieu from Institut Pasteur, Lille

Principal Investigator:

Amaury FARCE, PhD

Toxoplasmosis

Active 2022

Description

Study of toxic compounds for the cystic form of Toxoplasma gondii, and identification of the molecular target, in collaboration with Dr GISSOT Mathieu from Institut Pasteur, Lille

Principal Investigator

Amaury FARCE, PhD

Planned Projects

SINAPs v2

Planned Starting 2026

Development of version 2 of SINAPs, a tool designed to automate the identification and 3D visualization of key molecular interaction networks that drive protein activation and bioactive states

Principal Investigator:

Corentin BEDART, PhD, PharmD

SINAPs v2

Planned Starting 2026

Description

Development of version 2 of SINAPs, a tool designed to automate the identification and 3D visualization of key molecular interaction networks that drive protein activation and bioactive states

Principal Investigator

Corentin BEDART, PhD, PharmD

Completed Projects

PPM9

Completed 2019-2025

Study of a phosphatase essential for the Plasmodium replication cycle, PPM9, in collaboration with Pr ALIOUAT El Moukhtar from Institut Pasteur, Lille

Principal Investigator:

Amaury FARCE, PhD

PPM9

Completed 2019-2025

Description

Study of a phosphatase essential for the Plasmodium replication cycle, PPM9, in collaboration with Pr ALIOUAT El Moukhtar from Institut Pasteur, Lille

Principal Investigator

Amaury FARCE, PhD

P28GST - Design and evaluation of pharmacological tools for studying the immunomodulatory function of a parasitic protein in CD

Completed 2017-2021

Deciphered the dual anti-inflammatory mechanisms of the parasitic protein shP28GST through in silico modeling and in vivo validation to optimize future treatments for Crohn’s Disease

Principal Investigator:

Amaury FARCE, PhD

Team Members:

Corentin BEDART

P28GST - Design and evaluation of pharmacological tools for studying the immunomodulatory function of a parasitic protein in CD

Completed 2017-2021

Description

Studies of schistosome-host interactions have revealed that the regulation of host immune activity is involved in schistosome survival. The use of complete schistosome eggs has shown value in the treatment of inflammatory diseases, especially IBD. Previous research conducted at U995 identified a 28 KDa anti-oxidant, pro-Th2 glutathione S transferase (shP28GST). These results were validated in an animal model of colitis and enabled the initiation of a Phase II clinical trial in CD (ACROHNEM). Glutathione production is responsible for the antioxidant activity and an increase in the prostaglandin D2 level. The purpose of this project was to determine which of these activities was responsible for the reduction in intestinal inflammation. In silico analysis of the active site helped define the pharmacophoric elements required to bind P28GST. Further refinements provided information about the enzyme’s two mechanisms of action on the atomic level. On this basis, compounds able to selectively inhibit one of the activities were virtually screened. These were tested in vitro for their inhibitory potential in an enzymatic assay for GST activity; a second assay was used to confirm their lack of effect on PGD2 production, and vice versa. The molecules with an interesting activity profile at that stage were subsequently tested in an in vivo model of TNBS-induced colitis, once the absence of toxicity had been confirmed.

Principal Investigator

Amaury FARCE, PhD

Team Members

Corentin BEDART - PhD Student

Interested in Collaboration?

We're always open to new collaborations with academic and industrial partners