M1 - Epigenetics, Genetics, and Cell Biology (EpiGenBio)

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The EU will first address the main communication pathways between normal cells and intracellular transduction pathways encountered in physiological and neurophysiological mechanisms. Thus, G protein-coupled receptors (GPCRs) will be studied, namely their structure, function, and modulation by interaction proteins involved in particular in the phenomenon of desensitization. The main intracellular pathways activated by membrane GCRs will be addressed (MAP kinase pathways, PI3 kinase, etc.).

Next, a significant portion of the course will focus on calcium signaling and Ca2+ homeostasis, Ca2+ being a ubiquitous signal in cellular signaling. Calcium homeostasis will be studied in particular during the response of lymphocytes after antigen stimulation. Furthermore, the production of oxygen free radicals, which cause 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 will allow us to recap all the topics previously discussed in the course. The endocannabinoid system is responsible for multiple central and peripheral regulations.

Finally, two other topics will be addressed: the blood-brain barrier, which allows for highly integrated cellular communication between two environments, and the pancreatic β-cell, whose activity is crucial for regulating blood sugar levels through insulin secretion.

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The program offers refresher courses 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. Cell Adhesion & Signaling: Cell-cell and cell-extracellular matrix adhesive structures, their molecular organization and dynamics. Functions and regulation during development and pathogenesis. Regulation by signaling pathways. Mechanotransduction.

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

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

5. Stem cells: cell differentiation, totipotency, pluripotency, and multipotency; embryonic, adult, and cancer stem cells.

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

Various study models are presented to introduce the importance of biological diversity in the discovery of cellular and molecular mechanisms, as well as in understanding 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, totipotency, pluripotency, 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 testing reminders

Nature of mutations (loss-of-function; gain-of-function), concept of "master gene," clonal analysis (generation of somatic or germline clones), concept of cellular autonomy....

-Genetic models and methods.

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

-Positional information, genes with maternal effects, and the establishment of asymmetry.

Models and mechanisms of positional information = induction, Spemann and Mangold's experiment, organizing centers, concept of morphogens in invertebrates and vertebrates

-Establishment of axes: anteroposterior, dorsoventral.

Genetic screens: genes with maternal effects and genes with zygotic effects. Cell communication and signaling pathways: in establishing the dorsoventral axis, in limb formation, in establishing cell fate (some examples: nervous system: lateral inhibition process, etc.).

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

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

-Signaling and transcriptional networks

Transcriptional regulation during development, regulatory sequences during evolution, concept of gene networks. Coupling of transcription and signaling pathways in cell fate.

-Transcriptional program memory through epigenetic mechanisms:

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

Involvement of epigenetic mechanisms during cell differentiation

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Two- to four-month internship in an organization (research laboratory, company, etc.) in France or abroad

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Internship lasting more than four months in an organization (research laboratory, company, etc.) in France or abroad

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Cell culture is a basic technique in laboratories and is constantly evolving. It is important to understand its fundamentals, which are often poorly understood despite being an essential methodology in research and industry.

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The TER aims to prepare students to organize and carry out an in-depth bibliographic analysis that will enable them to approach their internship with knowledge of the state of the art in the field, in particular in order to produce a relevant and thoughtful introduction to their experimental work.

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