EU Master 1, Boarding School Track

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This course unit aims to reinforce and illustrate the knowledge acquired in the course unit “Molecular Bases of Infectious Diseases” through the analysis of scientific publications on topics in infectious diseases. Publications employing a variety of molecular and cellular approaches in bacteriology, parasitology, and virology—ranging from the most traditional to the most recent—are analyzed with the students.

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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 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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This course unit consists primarily of lectures covering the molecular aspects of infectious diseases (bacteriology, virology, parasitology)

Bacteriology: The nature of infectious agents. Methods for studying pathogenesis (in vivo, in vitro, in silico, and post-genomic research technologies) Strategies of pathogenic bacteria for survival within hosts: Bacterial adhesion to eukaryotic cells, antigenic variation and phase variation, invasion of non-phagocytic eukaryotic cells, mechanisms of resistance to phagocytosis, mechanisms of bacterial survival within phagocytic cells, regulation of membrane permeability, bacterial secretion systems (types I, II, III, IV, V, and VI), iron acquisition mechanisms, bacterial exotoxins, bacterial biofilms, examples of environmental regulation (thermoregulation, quorum sensing, etc.).

Parasitology: Organization and cellular physiology of major pathogens within parasitic unicellular eukaryotes (invasion and modification of the host cell; metabolic characteristics and therapeutic targets); Genetics and Molecular Biology (genome organization, antigenic variation); Pathophysiology and evasion of the immune response

Virology: Molecular mechanisms of the viral life cycle; Expression of viral genomes; Viral transformation; Viral replication strategies; Plasticity of viral genomes; Structural significance of viruses in host-virus interactions; 

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The course is taught by faculty members from the departments of medicine, science, and pharmacy. It consists of 42 hours of lectures and supervised work divided into 7 themes (see Syllabus), including two series of article presentations: the first series focuses on articles selected by the instructors for each theme, and the second series features articles chosen by the students. At the end of each course unit, students organize a mini-symposium where the articles are presented. They write abstracts of these articles for the journal *Medecine-Sciences*.

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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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