M1 - Epigenetics, Genetics and Cell Biology (EpiGenBio)

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The main communication pathways between normal cells and intracellular transduction pathways, encountered in physiological and neurophysiological mechanisms, will be discussed, such as G protein coupled receptors (GPCRs), their structure, function and modulation by interacting proteins involved in the desensitization phenomenon. The main intracellular pathways activated by GPCRs will be discussed (MAPkinase, PI3kinase, etc...).

Secondly, an important part of the course will focus on calcium signaling and Ca2+ homeostasis; Ca2+ being a ubiquitous signal in cell signaling. Calcium homeostasis will be studied in particular during the response of lymphocytes after antigenic stimulation. Moreover, the production of oxygenated free radicals, at the origin of oxidative stress, is dependent on intracellular Ca2+. The physiological role of free radicals will be discussed, as well as their involvement in oxidative stress. In this context, the pathways of protection against oxidative stress will also be studied.The following chapter will address the endocannabinoid system which allows to recapitulate all the themes that will be evoked previously in the course. The endocannabinoid system is at the origin of multiple central and peripheral regulations.

Finally, two other themes will be addressed: the blood-brain barrier which allows to evoke the cellular communication in a very integrated way between two environments and the -pancreatic cell whose activity is crucial for the regulation of glycemia by the secretion of insulin.

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The aim of this course is to introduce functional genomics technologies and to present examples of biological questions that can be asked using them.

This unit aims to present "omics" functional genomics technologies, and some biological questions that they can address.The lectures are given by both associate professors and researchers.

Introduction to functional genomics: approaches, concepts and methods

An introduction to functional Genomics: approaches, concepts and methods

V. Coulon, UM / IGMM

Genome organization / Organisation des génomes

Techniques de séquençage / DNA sequencing methodsL. Journot, IGF

3D genome organization J. Poli, UM / IGH

Genome topological organisation and replication-V. Coulon, UM / IGMM

Régulation spatio-temporelle de l'expression des génomes / Spatio-temporal regulation of gene expressionTranscriptionEpissage / Splicing-V. Coulon, UM / IGMM

Non-coding RNAsV. Coulon, UM / IGMM

Interactomics / InteractomiqueIan Robbins, UM / IGMM

Proteomics and Pharmacogenomics / Protéomique et pharmacogénomiqueC. Bécamel, UM / IGF

Animal Models / Modèles animaux

Using Mice in Functional Genomics F. Poulat, IGH

La Drosophile en génomique fonctionnelle / Using Drosophila in Functional Genomics -F. Juge and S. Chambeyron, IGH

Scientificarticles analysis and presentation(15min + 10 min discussion per group of 3 students)

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The program offers a refresher course and an in-depth study of the major concepts and methodologies of cell biology, organized around different themes:

Cytoskeleton:Introduction to the different types of cytoskeleton. Polymerization properties of actin and tubulin. Proteins associated with the cytoskeleton and regulating polymerization. Molecular motors. Principles of cell migration.

Cellular Adhesion & Signaling: Adhesive structures cell-cell and cell-extracellular matrix, their molecular organization and dynamics. Functions and regulations during development and pathogenesis. Regulation by signaling pathways. Mechanotransduction.

3. addressing and cell trafficking: Ubiquitination and proteasome. Addressing to subcellular compartments, endocytosis and secretion pathways. Molecular basis of vesicular transport, budding, fusion, molecular motors. Signaling in membrane trafficking, genetic diseases related to trafficking and detour by pathogens.

4.cell cycle:Historical introduction. Molecular regulation of the cell cycle. Mitotic spindle, microtubule dynamics and molecular motors, chromosome attachment mechanisms, checkpoints, regulation of mitosis exit and cytokinesis. Mitotic disorders associated with cancer cells.

5. stem cells: cell differentiation, toti-, pluri- and multipotency, embryonic, adult and cancer stem cells

6. programmed cell death: apoptosis, autophagy, necrosis. Stages and modalities of apoptosis, signaling pathways involved. Role in the maintenance of homeostasis. Pathophysiological consequences of deregulation of programmed cell death.

Different study models are presented, in order to introduce the importance of the contribution of biological diversity in the discovery of cellular and molecular mechanisms, as well as in the understanding of human pathologies.

The program offers a refresher of knowledge and an in-depth study of the major concepts and methodologies of cell biology, organized around different themes:

1. Cytoskeleton: Introduction to the different types of cytoskeleton. Polymerization properties of actin and tubulin. Proteins associated with the cytoskeleton and regulating polymerization. Molecular motors. Principles of cell migration.

2. Cellular Adhesion & Signaling: Cell-cell and extracellular cell-matrix adhesive structures, their molecular and dynamic organization. Functions and regulations during development and pathogenesis. Regulation by signaling channels. Mechanotransduction.

3. Addressing and cell traffic: Ubiquitination and proteasome. Addressing to subcellular compartments, endocytosis and secretion pathways. The molecular bases of vesicular transport, budding, fusion, molecular motors. Signaling in membrane trafficking, genetic diseases linked to trafficking and diversion by pathogens.

4. Cell cycle: Historical introduction. Molecular regulation of the cell cycle. The mitotic spindle, microtubule and molecular motor dynamics, chromosome attachment mechanisms, checkpoints, regulation of mitosis output and cytokinesis. Mitotic disorders associated with cancer cells.

5. Stem cells: cell differentiation, toti-, pluri-and multipotency, embryonic, adult and cancer stem cells.

6. Programmed cell death: Apoptosis, autophagy, necrosis. Stages and modalities of apoptosis, signaling pathways involved. Role in maintaining homeostasis. Physiopathological consequences of deregulation of programmed cell death.

Different study models are presented, in order to introduce the importance of the contribution of biological diversity in the discovery of cellular and molecular mechanisms, as well as in the understanding of human pathologies

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-A general introduction to developmental biology

How do cells build a multicellular animal organism from a single genome? Genotype/phenotype relationship.

-Genetic analysis reminders

Nature of mutations (loss-of-function; gain-of-function), notion of "master gene", clonal analysis (generation of somatic or germinal clones), notion of cell autonomy ....

-Genetic models and methods.

Study of regulatory regions, establishment of transgenic lines, enhancer trap, reporter genes (GFP, mCherry...), model organisms (drosophila, c.elegans, mice...).Use of FLP/FRT, CRE-LOX, UAS-GAL4-GAL80, AttpP/B-PhiC31, CRISPR etc.

-Positional information, maternal effect genes and the establishment of assymetry.

Models and mechanisms of positional information =induction, Spemann and Mangold experiment, organizing centers, notion of morphogen in invertebrates and vertebrates

-Establishment of the axes: antero-posterior, dorso-ventral.

Genetic screens: genes with maternal effects and genes with zygotic effects.Cellular communication and signaling pathways: in the establishment of the dorso-ventral axis, in the formation of limbs, in the establishment of cell fate (some examples: Nervous system: lateral inhibition process ...).

-Segmentation: the gap, pair rule and segmental polarity genes.

Segmentation in invertebrates and somitogenesis in vertebrates, dynamic aspects (establishment and maintenance).

-Signaling and transcriptional networks

Transcriptional regulations during development, regulatory sequences during evolution, concept of gene networks. Transcriptional coupling and signaling pathways in cell fate

-The memory of transcriptional programs by epigenetic mechanisms:

Hox homeotic genes and segmental identity.Evo-Devo concepts.Polycomb and Trithorax complexes.

Involvement of epigenetic mechanisms during cell differentiation

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Two to four month internship in a structure (research laboratory, company, etc.) in France or abroad

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Internship of more than 4 months in a structure (research laboratory, company,...) in France or abroad

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Cell culture is a basic technique in the laboratory and is constantly evolving. It is important to know the basics of cell culture, which are often not well known, even though it is an essential methodology in research and also in industry.

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The aim of the TER course is to prepare the student to organize and carry out an in-depth bibliographical analysis in order to approach the internship with a knowledge of the state of the art in the field and to produce a relevant and well thought-out introduction to his experimental work.

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