Dr. Charline Fagnen
- Position: Research Fellow (Computational Biophysics)
- Areas of expertise: Molecular Dynamics, Coarse-Grains, All-atom simulations, Molecular Modelling, Channel, Gating, Membrane Protein, Mechanism, Method Development
- Email: C.Fagnen@leeds.ac.uk
- Location: Level 7 LIGHT Laboratories - LICAMM
- Website: LinkedIn | Researchgate | ORCID
I studied Chemistry at Cergy-Pontoise before focusing on Cheminformatics at the University of Strasbourg. From 2016 to 2020, I realized a PhD in Structural Bioinformatics at Sorbonne University under the supervision of Pr. Catherine Vénien-Bryan and Dr. David Perahia (ENS Paris-Saclay). My thesis work was based on studying the gating mechanism of KirBac3.1 channels.
From November 2020 to November 2021, I moved to the University of Caen as a postdoctoral researcher, where I studied the aggregation mechanism of the tau protein involved in Alzheimer’s disease under the supervision of the Pr. Jana Sopkova-de Oliveira Santos and the Pr. Anne Sophie Voisin-Chiret.
In March 2022, I moved to the University of Leeds to investigate the Piezo channel gating and the impact of the shear stress on it. I work under the supervision of Dr. Antreas Kalli, who obtained the funds from the British Heart Foundation for this project.
I am interested in investigating health and pharmaceutical issues by in silico methods and method development to improve the performance of the used tools.
My thesis project was focused on the KirBac3.1 channel, a homologous of Kir2.1 whose mutations can lead to rare diseases such as Andersen syndrome. My work was divided into three parts: i) the study of the gating mechanism of KirBac3.1 WT, ii) the impact of two mutations S129R and W46R that respectively opens and closes the channel, iii) the determination of the cryo-EM structure of human Kir2.1 channel. To perform the two first goals, we used a recent method called MDeNM (developed by Dr. Perahia) that combined all-atom molecular simulations and normal modes to access a larger conformational space. Regarding the last goal, I obtained a final model of 6.2Å that was improved at 4.30Å (PDB:7ZDZ ) by the lab after I left. Finally, I also had the opportunity to work on a method development called MDeNM-EMFit; it adapts MDeNM method to perform flexible fitting of a structure in its cryo-EM map.
During my postdoctoral time in Caen, I studied tau protein aggregation, one of the two phenomena responsible for Alzheimer’s disease. Thanks to all-atom simulations, I determined at the atomic level different mechanisms involved in this aggregation. I also worked on the impact of potential drug candidates like palmatine chloride.
Since I moved to Leeds, I have been focusing on the human mechanosensitive ion channel Piezo1. hPiezo1 is crucial in various mechanotransduction processes and is responsible for proprioception, touch, balance, and hearing. In case of mutations, the channel could cause lymphedema or hematological disorders (hemolytic anemia). My role is to investigate the Piezo1 gating in red blood cells by multi-scale molecular dynamics simulations.
- 2013 : Bachelor’s degree in Chemistry (Licence), University of Cergy-Pontoise, France
- 2015 : Master’s degree in Cheminformatics, University of Strasbourg, France
- 2020 : PhD in Bioinformatics and Biology of the Systems, Sorbonne Université, France
Research groups and institutes
- Leeds Institute of Cardiovascular and Metabolic Medicine