Analysis of Functionally Relevant Chromatin - Strasbourg, France - IGBMC Institut de Génétique et de Biologie Moléculaire et Cellulaire CERBM - GIE

Description

Analysis of functionally relevant chromatin organizations by artificial intelligence tools applied to cryo-electron tomography data:

• Réf

-
ABG-111388

• Sujet de Thèse 22/02/2023
• Contrat doctoral
• IGBMC Institut de Génétique et de Biologie Moléculaire et Cellulaire CERBM
• GIE
• Lieu de travail
• Strasbourg
• Grand Est
• France
• Intitulé du sujet
• Analysis of functionally relevant chromatin organizations by artificial intelligence tools applied to cryoelectron tomography data
• Champs scientifiques
• Science de la donnée (stockage, sécurité, mesure, analyse)
• Biologie
• Mots clés image processing, data mining, artificial intelligence, deep learning, computer vision, cryoelectron microscopy chromatin, epigenetics
  Description du sujet:

Tomographic reconstructions obtained from flash frozen samples represent the ultimate quality of the structural information of cell organization available to date, reaching near-atomic resolution.

However, the information extraction from cryo-electron tomography (cryo-ET) reconstructions remains challenging particularly because of a high noise and deformations due to a limited tilt angular range accessible in cryo-ET.

Emerging approaches based on computer vision and deep learning offer new opportunities to overcome these challenges to take full advantage of cryo-ET for understanding biological functions.

Recent work by the team has demonstrated the value of combining cryo-ET and deep learning denoising approaches to annotate nucleosomes and DNA linkers in their functional environment of the cell nucleus, preserved in a near-native state.

The aim of this project is to further develop this methodological synergy by developing new computational tools based on deep learning and involving 3D segmentation, pose estimation and deformable image registration to extract information from chromatin tomograms at three structural levels:
organization of chromatin domains, local geometry of nucleosome fibers and nucleosome conformation.

Comparative analysis of the local structural landscapes of active and inactive chromatin will reveal mechanisms of epigenetic regulation based on chromatin structure.

Nature du financement:

• Contrat doctoral

Précisions sur le financement:


Présentation établissement et labo d'accueil:

• IGBMC Institut de Génétique et de Biologie Moléculaire et Cellulaire CERBM
• GIE

Located in the Illkirch-Graffenstaden Innovation Park, the IGBMC is at the heart of the Alsace Biovalley competitiveness cluster. Interacting with other academic and industrial players, the Institute is involved in several large-scale projects to promote its research and equipment.

As an international biomedical research center, one of the main missions of the IGBMC is to train students in the most up-to-date biology.

Thanks to an excellent training environment, the institute currently welcomes nearly 250 students and post-doctoral fellows from some 40 different countries.

The institute has strong links with the Ecole doctorale des sciences de la vie et de la santé (ED 414) of the University of Strasbourg and is the only one authorized to deliver PhD degrees in biology.

Since 2018, the IGBMC has also participated in the IMCBio University Research School (EUR), whose objective is to offer high-level cross-disciplinary training in biology research from the master's to the doctoral level.

The Department of Integrated Structural Biology (ISB) of IGBMC develops cross-disciplinary research at the interfaces of biology, biochemistry, physics, and medicine.

The department addresses several thematic axes covering the regulation of gene expression, epigenetics, cell and developmental biology, pathological mechanisms, and molecular medicine.

The 12 teams of the department aim at understanding the molecular and atomic mechanisms of physiological or pathological processes by correlating the structural information with the functional properties of their molecular components.

Complex biological systems are analyzed by a combination of methods to integrate spatial, temporal, and functional dimensions.

• The ISB provides a leadingedge scientific and technological environment in integrated structural biology to address the structure and function of biological systems, notably on gene expression, from the atomic, molecular to the tissue scales. The ISB hosts the French and European Infrastructures for Integrated Structural Biology, FRISBI and Instruct-ERIC which comprises advanced electron microscopy facilities equipped with cuttingedge instrumentation such as 2 Titan Krios and 1 Glacious cryo electron microscopes, cryo Focused Ion Beam Scanning Electron Microscope (FIB/SEM) and superresolution fluorescence microscopy. In addition, the EM facility has a suite of associated equipment for sample preparation with a focus on cryo methods and dedicated computing resources for image processing and data mining.

Site web:


Intitulé du doctorat:

• PhD degree in biolo