Mots-Clés

drug screening microscopy image features statistics GUI

Description

Offer: Master 2 - Computational analysis of data from functional screening of drugs on cellular models

Background: The discovery of new anti-cancer treatments remains a major challenge in public health, particularly due to problems of toxicity of current molecules (side effects) and the development of mechanisms of resistance of cancer cells to these treatments in order to survive and metastasize (relapses). With the aim of identifying new molecules capable of killing cancer cells without impacting normal cells and targeting cancer cells that have developed drug resistance mechanisms, the Screening for BioActive Molecules (CMBA) platform at CEA Grenoble screens libraries of chemical molecules on different cancerous versus non-cancerous cell models. Currently several molecules have been selected for their preferential toxicity on cancer cells versus healthy cells. The objective is to characterize the mechanisms of action of these compounds using different biological tests to identify the mechanisms of toxicity or the signaling pathways involved. These studies are carried out on living cells treated with molecules at a dose or dose response, by automated imaging, and over time (kinetics). This type of high-throughput experiment generates a very large quantity of microscopy images, which are then analyzed in order to extract quantitative parameters (number of living or dead cells, area, fluorescence intensity, etc.).

Objective: This internship will consist of the development of a data analysis workflow, associated with a graphical user interface, taking as input multiple quantitative features extracted from microscopy images of cells exposed to drugs, and being able to perform statistical analyses and visualizations relevant to evaluate drug sensitivity data.

Workplan: The intern will carry out its development and analysis work within a working group made up of research members of the CMBA platform, a PhD student and a senior researcher in bioinformatics. He/she will be able to build on the data analysis approaches already in place on the CMBA platform to extend and automate them in order to reduce analysis times while gaining data exploratory and interaction capabilities.

Host laboratory: The intern will be hosted in the MODAL (Multiscale bioinformatics & digital health) group (https://www.bge-lab.fr/en/GenChem/Research/MODAL) within the “Genetics & Chemogenomics” team of the Interdisciplinary Research Institute of Grenoble (IRIG) of the CEA Grenoble. He/she will be supervised by Emmanuelle Soleilhac, head of the High Content Screening Imaging service from the CMBA platform (https://www.bge-lab.fr/en/Pages/CMBA/Cell-profiling-using-automated-microscopy-HCS-HCA.aspx), and co-supervised by Christophe Battail, expert in bioinformatics and computational biology. He/she will evolve in a multidisciplinary research environment composed of bioinformaticians and biologists.

Candidate profile:

Knowledge and skills in bioinformatics: R programming language, Dash/Shiny framework, unix command line, statistics

Professional aptitude: curiosity and desire to improve their scientific and technological skills, rigor and organization, a ability to work in a team and interact with other students, engineers and researchers.

Job contract:

6-month master's internship starting in January 2024.

Please send a CV, a cover letter and the name of a referee to emmanuelle.soleilhac@cea.fr and christophe.battail@cea.fr.