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 signal transduction pathways encountered in physiological and neurophysiological mechanisms. Thus, G protein-coupled receptors (GPCRs) will be studied, specifically their structure, function, and modulation by interacting proteins involved, in particular, in the phenomenon of desensitization. The main intracellular pathways activated by membrane-bound GPCRs will be discussed (MAP kinase pathways, PI3 kinase, etc.).

Next, a significant portion of the course will focus on calcium signaling and Ca²⁺ homeostasis, as Ca²⁺ is a ubiquitous signal in cellular signaling. Calcium homeostasis will be studied in particular in the context of the lymphocyte response following antigenic 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 protective mechanisms against oxidative stress will also be examined.The following chapter will address the endocannabinoid system, which serves to summarize all the topics previously covered in the course. The endocannabinoid system is responsible for numerous central and peripheral regulatory processes.

Finally, two other topics will be covered: the blood-brain barrier, which provides a framework for discussing cellular communication in a highly integrated manner between two environments, and the pancreatic β-cell, whose activity is crucial for regulating blood glucose levels through insulin secretion.

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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 various themes:

1. Cytoskeleton: Introduction to the different types of cytoskeletons. Polymerization properties of actin and tubulin. Proteins associated with the cytoskeleton that regulate 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 trafficking and targeting: Ubiquitination and the proteasome. Targeting to subcellular compartments; endocytosis and secretion pathways. The molecular basis of vesicular transport: budding, fusion, and molecular motors. Signaling in membrane trafficking; genetic diseases associated with trafficking; and hijacking by pathogens.

4. Cell Cycle: Historical Overview. Molecular Regulation of the Cell Cycle. The mitotic spindle, microtubule dynamics and molecular motors, mechanisms of chromosome attachment, checkpoints, regulation of mitotic exit, and cytokinesis. Mitotic abnormalities 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. Pathophysiological consequences of dysregulation of programmed cell death.

Various research models are presented to highlight the importance of biological diversity in the discovery of cellular and molecular mechanisms, as well as in the understanding of human diseases.

The program offers a review of key concepts 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 involved in 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 regulation during development and pathogenesis. Regulation by signaling pathways. Mechanotransduction.

3. Addressing and cell traffic: Ubiquitination and the proteasome. Transport to subcellular compartments, endocytosis, and secretion pathways. The molecular basis of vesicular transport, budding, fusion, and molecular motors. Signaling in membrane trafficking, genetic diseases linked to trafficking, and disruption 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 mitotic 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 mechanisms of apoptosis; signaling pathways involved. Role in maintaining homeostasis. Pathophysiological consequences of dysregulation of programmed cell death.

Various study models are presented to highlight the importance of biological diversity in the discovery of cellular and molecular mechanisms, as well as in the understanding of human diseases.

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-A General Introduction to Developmental Biology

How do cells build a multicellular animal organism from a single genome? The genotype-phenotype relationship.

-Genetic Testing Reminders

Nature of mutations (loss-of-function; gain-of-function), the concept of a “master gene,” clonal analysis (generation of somatic or germline clones), the 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, and other 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, the concept of morphogens in invertebrates and vertebrates

-Defining the axes: anteroposterior, dorsoventral.

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

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

Segmentation in invertebrates and somite formation in vertebrates: dynamic aspects (establishment and maintenance).

-Signaling and transcriptional networks

Transcriptional regulation during development, regulatory sequences throughout evolution, and the concept of gene networks. The interplay between transcription and signaling pathways in cell fate

-Transcriptional program memory via epigenetic mechanisms:

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

The Role of Epigenetic Mechanisms in Cell Differentiation

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

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An internship lasting more than 4 months at an organization (research laboratory, company, etc.) in France or abroad

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Cell culture is a fundamental technique in laboratories and is constantly evolving. It is important to understand its basics, which are often poorly understood, even though it is an essential methodology not only in research but also in industry.

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The EU TER course aims to prepare students to organize and conduct an in-depth literature review that will enable them to approach their internship with an understanding of the state of the art in the field, in particular to produce a relevant and well-thought-out introduction to their experimental work.

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