M1 - Cancer Biology

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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The “Cellular Pathophysiology and Cancer” course unit aims to provide students with the knowledge necessary to pursue the “Cancer Biology” track in the M2 program. The course unit is organized as a lecture, consisting of an introductory section followed by a section on current research in the laboratories. Students are required to give an oral presentation on a scientific article (usually in pairs).

The goal of the cellular pathophysiology and cancer course is to provide the scientific background necessary to succeed in the M2 program in cancer biology. Each lecture is structured as a seminar, beginning with a general introduction to the field and followed by a more specialized focus on research conducted in laboratories. Students are required to prepare an oral presentation based on the analysis of a scientific article (usually in pairs).

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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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Three main topics are covered:

-A study of weight and thermal homeostasis in relation to a model of dysfunction: obesity. This will involve an examination of energy balance—including food intake and energy expenditure, which consists of basal metabolism, physical activity, and adaptive thermogenesis (AT)—and their respective regulatory mechanisms.

-Study of biological rhythms, including a description of the nature and properties of biological rhythms (ultradian, circadian, and infradian), a description of endogenous circadian oscillators, and a detailed presentation of the molecular mechanisms of circadian clocks.

-Study of the various stages and physiological principles of respiration. The theoretical lectures will be supplemented by tutorial sessions (TD). The tutorial sessions are based on the study of documents and the analysis of scientific articles in English. The selection of scientific materials is intended to illustrate the interplay among the various topics covered and, thereby, the concept of integrative physiology.

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Neuromuscular Physiology:

Skeletal striated muscle: The neuromuscular junction; Muscle contraction/relaxation; Myotypology; Plasticity; Muscle metabolism.

Neuromuscular Diseases: Causes; symptoms; clinical diagnosis (clinical examinations; laboratory tests): EMG, blood tests, functional tests, etc.; Muscular dystrophies: Duchenne muscular dystrophy; Becker muscular dystrophy; facioscapiohumeral muscular dystrophy (FSHD). Facioscapiohumeral muscular dystrophy (FSHD): zebrafish model; mouse model; cellular models; clinical trials.

Respiratory Physiology:

Respiratory Physiology: Anatomy of the respiratory system; the mechanism of respiration; gas exchange; transport of respiratory gases in the blood; regulation of respiration

Respiratory Assessment in Small Animals: Why Assess Respiratory Function in Small Animals? Plethysmography; in vitro contractile force.

Functional Respiratory Tests: performance and interpretation of respiratory tests in human medicine; spirometry: Level 1 and Level 2; pulmonary diffusion capacity; arterial blood gases; specific tests of the respiratory muscles; 6-minute walk test; exercise testing; tests involving exposure to high altitude.

Cardiovascular Physiology:

Review of cardiac anatomy: size, location, and orientation; the heart’s envelope; the layers of the heart wall; the heart’s chambers and major vessels; the flow of blood through the heart; cardiac valves; blood supply to the heart: coronary circulation; properties of cardiac muscle tissue.

Review of cardiac physiology: regulation of the baseline heart rate; the cardiac conduction system; changes in the baseline heart rate: extrinsic innervation of the heart; electrocardiography; mechanical phenomena: cardiac cycle; cardiac output; regulation of stroke volume; regulation of heart rate.

Review of vascular physiology: anatomy of the circulatory system; lymphatic system; structure of the vascular wall; blood pressure; vascular smooth muscle and vasomotor function; endothelial function.

Vascular function and dysfunction; functional assessment: measurement of arterial distensibility; measurement of arterial wave velocity; pharmacological assessment of endothelium-dependent vasomotility; ultrasonographic assessment; echo-tracking; ultrasound and Doppler ultrasound.

How can vascular function be assessed experimentally? Isolated arterial ring model; Cardiac Doppler ultrasound: a powerful tool in clinical and experimental research; Ultrasound: anatomical and functional analysis; Doppler: flow analysis; Application to animal models.

Translational research: example—myocardial ischemia-reperfusion (myocardial infarction); Animal models; perfused isolated heart (Langendorf); Isolated cardiomyocytes; Cardioprotection techniques.

Endocrinology: Weight Balance

Description of eating behavior; Energy balance; Central regulatory structures of food intake; Regulatory mechanisms of food intake; Factors modulating appetite and food intake; Nutritional assessment; Eating disorders; Functional assessment: impedance measurement; DEXA (dual-energy X-ray absorptiometry); MRI; Assessment of energy expenditure: calorimetry.

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This course aims to provide a broad overview of emerging interdisciplinary quantitative fields in the biosciences, ranging from cutting-edge experimental techniques in microscopy and synthetic biology to systems-based approaches.

In an innovative way, these methodological aspects will be presented in the context of biological and biophysical concepts such as the robustness and optimality of biological systems, gene regulation, and the fundamental principles underlying the organization of membranes and the genome.

The main topics will first be introduced through traditional lectures and then explored through individual or team projects, in which students will learn to apply specific techniques using examples and see how these techniques can be used to investigate specific biological questions. These projects will involve literature reviews, the use of existing code, or the development of new code (depending on the student’s experience) and will account for half of the final grade.

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

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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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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 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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Are you a third-year undergraduate or first-year graduate student in the Languedoc-Roussillon region? Would you like to work in small groups with students from other programs on a project-based approach, using an unused scientific patent? Would you like to be guided and challenged by professional startup coaches? Sign up for the PEPITE Patent Project to present a plan for an innovative startup based on the commercialization of a real patent provided by a local research team that will welcome you with open arms!

Why?

-Because you can start your own business no matter what field you're in

-To be selected by an incubator-type support organization

-To help you build a network in the fields of entrepreneurship and innovation

PEPITE Patent Project—what is it? A teaching unit consisting of key activities:

- a 3-day "tool training" seminar

-regular meetings with the coaches

-Deliverables to be submitted: summary report, market research, business plan

- a 10-minute final pitch to present your innovative company

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