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 characterizing the tracks. Its purpose 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 according to the students recruited, in order to achieve a more homogeneous start to the course. Students will be immersed in different role-playing games divided into small groups. They will have to solve enigmas using their knowledge in biology, physics/mathematics, chemistry and programming, like 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 bioscience, ranging from advanced 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 robustness and optimality of biological systems, gene regulation and the fundamental principles underlying membrane and genome organization.

The main topics will be introduced first 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 literature reviews, use of existing code, or development of new code (depending on the student's experience) and will constitute half of the final assessment.

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

The topics covered in the Neurobiology of Behavior EU will include:

-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 study synaptic plasticity: electrophysiology, optogenetics, animal models, behavioral tests-Regulatory factors of synaptic plasticity including genetics and epigenetics-Plasticity/memory relationship-Neurobiology of memory, forgetting and reconsolidation

-Neurobiology of emotions

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

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The program covers the important basic notions of gene organization and different levels of gene regulation, as well as the essential notions of human population genetics that play an important role as risk factors.The molecular mechanisms involved in monogenic or polyfactorial diseases are presented using specific examples. The module also provides an overview of the new technological tools available (pan-genomic techniques, high-throughput genotyping, etc.), which have led to major advances in this field, as well as 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 model of dysfunction: obesity. For this purpose, the energy balance with food intake and energy expenditure composed of basic metabolism, physical activity and adaptive thermogenesis (AT) and their respective regulation will be addressed.

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

-Study of the different stages and physiological principles of breathing. Theoretical lessons will be complemented by tutorials. The tutorials are based on document studies and the analysis of scientific articles in English. The choice of the various scientific supports aims at showing the interaction of the various approached topics and thus the concept of integrative physiology.

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Neuromuscular physiology:

Striated skeletal muscle: The neuromuscular junction; Contraction/muscle 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's myopathy; facioscapiohumeral muscular dystrophy (FSHD).Facioscapiohumeral muscular dystrophy FSHD: 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.

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

Cardiovascular physiology:

Reminder of the anatomy of the heart: size, location and orientation; envelope of the heart; 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 the cardiac muscle tissue.

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

Reminder of 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; echotracking; ultrasound and echodoppler.

How to evaluate vascular function experimentally?isolated artery ring model Cardiac Doppler: a fabulous 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; 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; Assessment of expenditure: 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:

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.

Cellular Adhesion & Signaling: Adhesive structures cell-cell and cell-extracellular matrix, their molecular organization and dynamics. Functions and regulations 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, genetic diseases related to trafficking and detour by pathogens.

4.cell cycle:Historical introduction. Molecular regulation of the cell cycle. 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 the maintenance of homeostasis. Pathophysiological 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.

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 intracellular transduction pathways, encountered in physiological and neurophysiological mechanisms, will be discussed, such as G protein coupled receptors (GPCRs), their structure, function and modulation by interacting proteins involved in the desensitization phenomenon. The main intracellular pathways activated by GPCRs will be discussed (MAPkinase, PI3kinase, etc...).

Secondly, an important part of the course will focus on calcium signaling and Ca2+ homeostasis; Ca2+ being a ubiquitous signal in cell signaling. Calcium homeostasis will be studied in particular during the response of lymphocytes after antigenic stimulation. Moreover, 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. In this context, the pathways of protection against oxidative stress will also be studied.The following chapter will address the endocannabinoid system which allows to recapitulate all the themes that will be evoked previously 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 allows to evoke the cellular communication in a very integrated way between two environments and the -pancreatic cell whose activity is crucial for the regulation of glycemia by the secretion of insulin.

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Two to four month internship in a structure (research laboratory, company, etc.) in France or abroad

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

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The physiology laboratory course allows to carry out recordings of cardiac action potential on the frog heart by the intracellular microelectrode technique. This is a qualitative and quantitative method of measuring the electrical activity of the heart muscle.

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Cell culture is a basic technique in the laboratory and is constantly evolving. It is important to know the basics of cell culture, which are often not well known, even though it is an essential methodology in research and also in industry.

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You are a student of L3/M1 level in Languedoc-Roussillon? Would you like to work in small groups with students from other courses and in project mode, using a dormant scientific patent? To be accompanied and challenged by professional coaches of business creation? Register to PEPITE Patent Project to present a project of creation of innovative company based on the exploitation of a real patent provided by a local research team which will open its doors to you!

Why?

-Because you can create your own business whatever your field of study

To be selected by an incubator-type support structure

-To create a network in the field of entrepreneurship and innovation

PEPITE Patent Project, what is it? A Teaching Unit made up of strong times:

a 3-day "tool training" seminar

-regular meetings with the coaches

-Deliverables to be submitted: summary 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 the student to organize and carry out an in-depth bibliographical analysis in order to approach the internship with a knowledge of the state of the art in the field and to produce a relevant and well thought-out introduction to his experimental work.

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