M1 - Experimental and Regenerative Medicine

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The Bootcamp is an intensive course at the beginning of the first semester, before the start of the courses that characterize the courses. Its aim is to refresh and/or bring students up to speed on the basics of mathematics, physics, computer science and biology.

The course will be adapted to suit the students recruited, with the aim of ensuring a more homogeneous start to the course. Students will be immersed in a variety of role-playing games, divided into small groups. They will have to solve enigmas using their knowledge of biology, physics/mathematics, chemistry and programming, as in an escape game over several days.

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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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Behaviors, whether determined by conscious or unconscious processes, are based on complex neurobiological underpinnings: they are underpinned by molecular and cellular modifications within the nervous system, modulating neural networks at the origin of motor and emotional processes that are linked to the individual's memory. These processes are fundamental in enabling the organism to develop an integrated behavioral response in close interaction with its environment, ensuring adaptation and survival for the individual and its species.

The topics covered in the Neurobiology of Behavior course are as follows:

-Gene-behavior

The relationship between genotype and phenotype -Impact of the environment -Attentional processes/Movement planning -Behavioral disorders (genetic and environmental aspects)

-Memory and synaptic plasticity

Methodological approaches to studying synaptic plasticity: electrophysiology, optogenetics, animal models, behavioral tests-Factors regulating synaptic plasticity, including genetics and epigenetics-Plasticity/memory relationship-Neurobiology of memory, forgetting and reconsolidation

-Neurobiology of emotions

Neurobiological substrates of emotions -Emotional functions -Disadaptation: Pathological aspects: Emotional disorders

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The program covers not only the basic notions of gene organization and the different levels of gene regulation, but also the essential notions of human population genetics, which play an important role as risk factors. Finally, the module provides an overview of the impact of this research on medical practice, through the development of cell therapy, gene therapy and pharmacogenomics.

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

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The physiology practical course enables you to record cardiac action potentials on frog hearts using the intracellular microelectrode technique. This is a qualitative and quantitative method for measuring the electrical activity of cardiac muscle.

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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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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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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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