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 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 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, trafficking-related genetic diseases and pathogen detour.

4 Cell cycle: Historical introduction. Molecular regulation of the cell cycle. The 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 maintaining homeostasis. Pathophysiological consequences of deregulation of programmed cell death.

Different study models are presented, to introduce the importance of the contribution of biological diversity to the discovery of cellular and molecular mechanisms, and to 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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The aim of the "Cellular Physiopathology and Cancer" course is to provide students with the knowledge they need to follow the "Cancer Biology" pathway in M2. The course is organized in the form of a lecture, with an introductory section followed by a section on current laboratory research. Students are required to present a scientific article orally (usually in pairs).

The aim of the cellular pathophysiology and cancer teaching unit is to provide the scientific background necessary to follow the cancer biology M2 program.Each lecture is organized as a conference starting with a general introduction of the field and followed by a more specialized emphasis on research done in laboratories. Students have to prepare an oral presentation based on the analysis of a scientific article (generally in pair).

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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, mouse...).Use of FLP/FRT, CRE-LOX, UAS-GAL4-GAL80, AttpP/B-PhiC31, CRISPR systems etc.

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

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

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

Cell communication and signalling pathways: in the establishment of the dorso-ventral axis, in limb formation, in the establishment of cell fate (some examples: Nervous system: lateral inhibition processes ...).

-Segmentation: gap, pair rule and segment 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, the concept of gene networks. Transcriptional coupling and signaling pathways in cell fate

-Epigenetic memory of transcriptional programs:

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

Involvement of epigenetic mechanisms in cell differentiation

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Three main themes are addressed:

-Study of weight and thermal homeostasis in relation to a dysfunctional model: obesity, by examining the energy balance with food intake and energy expenditure, comprising basic metabolism, physical activity and adaptive thermogenesis (AT), and their respective regulation.

-Study of biological rhythms, by describing the nature and properties of biological rhythms (ultradian, circadian and infradian), describing endogenous circadian oscillators, and detailing the molecular mechanisms of circadian clocks.

-Study of the different stages and physiological principles of breathing. Theoretical teaching will be complemented by tutorials (TD)TD sessions are based on document studies and analysis of scientific articles in English. The choice of scientific material is designed to demonstrate the interaction of the various themes covered, and hence the concept of integrative physiology.

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Teaching is done by teachers and/or researchers at the Faculties of Medicine, Sciences or Pharmacy, or at local research institutes.Course contents will be adapted to current scientific advances.

Teaching is organized in topics (lectures/tutorials, 4 to 5:30 hrs each);each includes an introduction and a seminar. In addition, for each topic, a group of students is in charge of presenting one or two recent scientific research articles.

Examples of subjects treated:

Immune adaptive responses, vaccination

Immune tolerance

Aging of the immune system

Metabolic regulation of the immune response

Immune response regulation by microbiota

Immune system-central nervous system interactions

Immunotherapy, therapeutic antibodies

The Unit is complemented by practical work by groups on a mini-research project that includes design of experiments, realization and analysis. Training is available in the use of flow cytometry data analysis software.Results are presented orally to the entire class.

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Neuromuscular physiology:

Striated skeletal muscle: The neuromuscular junction; Muscle contraction/release; Myotypology; Plasticity; Muscle metabolism.

Neuromuscular diseases:Causes; symptoms; clinical diagnosis (clinical examinations; laboratory tests): EMG, blood assays, functional tests, etc.; muscular dystrophies: Duchenne myopathy; Becker myopathy; facioscapiohumeral muscular dystrophy (FSHD).FSHD facioscapiohumeral muscular dystrophy: zebrafish model; mouse model; cell models; clinical trials.

Respiratory physiology:

Respiratory physiology: Anatomy of the respiratory system; mechanism of respiration; gas exchange; transport of respiratory gases by the blood; regulation of respiration.

Respiratory exploration in small animals: Why explore respiratory function in small animals? Plethysmography; in vitro contractile force.

Functional Respiratory Explorations: performance and interpretation of respiratory explorations in human pathology; spirometry: Level 1 and Level 2; pulmonary diffusion capacity; arterial blood gas; specific explorations of respiratory muscles; 6-minute walk test; stress test; explorations at altitude.

Cardiovascular physiology:

Anatomy of the heart: size, location and orientation; heart envelope; tunics of the heart wall; chambers and large vessels of the heart; blood flow in the heart; heart valves; blood supply to the heart: coronary circulation; properties of cardiac muscle tissue.

Reminder of cardiac physiology: regulation of basic rhythm; cardiac conduction system; modification of basic rhythm: extrinsic innervation of the heart; electrocardiography; mechanical phenomena: cardiac revolution; cardiac output; regulation of stroke volume; regulation of heart rate.

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

Vascular function and dysfunction; functional exploration: Arterial Distensibility Measurement; arterial wave velocity measurement; pharmacological exploration of endothelium-dependent vasomotricity; ultrasonographic exploration; echo-tracking; ultrasound and echodoppler.

How to assess vascular function experimentally: Isolated artery ring model Cardiac Doppler ultrasound: a fabulous tool for clinical and experimental research; Ultrasound: anatomical and functional analysis"; Doppler: flow analysis; Application to animal models.

Translational research: example of myocardial ischemia-reperfusion (myocardial infarction); animal models; isolated perfused heart (Langendorf); isolated cardiomyocytes; cardioprotective techniques.

Endocrinology: weight balance

Description of eating behavior; Energy balance; Central structures regulating food intake; Mechanisms regulating food intake; Factors modulating appetite and food intake; Nutritional assessment; Eating disorders; Functional exploration: impedancemetry; DEXA (X-ray photon absorption); MRI; Expenditure assessment: calorimetry.

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

The main topics will first be introduced with traditional lectures and will be developed through individual or team projects where students will learn to apply specific techniques through examples, and see how these can be used to explore specific biological questions. These projects will involve bibliographical studies, the use of existing code or the development of new code (depending on the student's experience) and will make up half of the final assessment.

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

A major part of the course will then focus on calcium signaling and Ca2+ homeostasis, Ca2+ being a ubiquitous signal in cell signaling. Calcium homeostasis will be studied in particular during the lymphocyte response to antigenic stimulation. In addition, 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. The following chapter will focus on the endocannabinoid system, summarizing all the topics covered earlier 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 evokes highly integrated cellular communication between two environments, and the -pancreatic cell, whose activity is crucial to the regulation of glycemia through insulin secretion.

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Two to 4-month internship in a research laboratory or company in France or abroad.

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The aim of the TER course is to prepare students to organize and carry out an in-depth bibliographical analysis, enabling them to approach their internship with a knowledge of the state of the art in the field, and in particular to produce a relevant and thoughtful introduction to their experimental work.

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

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Cell culture is a basic laboratory technique that is constantly evolving. It is important to know the basics, which are often poorly understood, even though it is an essential methodology in research and industry.

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Teaching is carried out by teacher-researchers from the UFRs of Medicine, Science and Pharmacy. It is organized into 42 hours of lectures and supervised work divided into 7 themes (see Syllabus) including 2 series of article presentations; 1 series on articles proposed by the lecturers in each theme. A second series on articles chosen by the students. At the end of the course, students organize a mini-colloquium at which the articles are presented. They write brief reviews of these articles for the journal Medecine-Sciences.

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Are you an L3/M1 student in Languedoc-Roussillon? Would you like to work on a dormant scientific patent in small groups with students from other disciplines, in project mode? Be supported and challenged by professional business creation coaches? Sign up for the PEPITE Patent Project to present a project for the creation of an innovative company based on the exploitation of a real patent supplied by a local research team that will open its doors to you!

Why?

-Because you can start your own business whatever your field of study.

To be selected by an incubator-type support structure

-Build a network in the field of entrepreneurship and innovation

PEPITE Patent Project, what is it? A teaching unit made up of a number of key moments:

a 3-day "tool training" seminar

-regular meetings with coaches

-deliverables: briefing note, market study, business plan

a 10-minute final pitch to present your innovative company

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