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 programs. Its purpose is to refresh and/or upgrade students' knowledge of the basics of mathematics, physics, computer science, and biology.

The course will be adapted to suit the students enrolled, with the aim of ensuring a more consistent start to the program. Students will be immersed in various role-playing activities in small groups. They will have to solve puzzles using their knowledge of biology, physics/mathematics, chemistry, and programming, as in an escape game lasting several days.

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This course unit aims to provide a broad overview of emerging quantitative interdisciplinary fields in biosciences, ranging from cutting-edge experimental techniques in microscopy and synthetic biology to systemic 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 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 bibliographic studies, the use of existing code, or the 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 substrates. They are underpinned by molecular and cellular changes within the nervous system that modulate the neural networks responsible for motor and emotional processes linked to an individual's memory. These processes are fundamental in enabling the organism to develop an integrated behavioral response in close interaction with its environment, thereby ensuring the adaptation and survival of the individual and their species.

The topics covered in the Behavioral Neurobiology course will be 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 genetic and epigenetic factors—The relationship between plasticity and memory—The neurobiology of memory, forgetting, and reconsolidation

-Neurobiology of emotions

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

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The program covers the important basic concepts of gene organization and different levels of gene regulation, as well as essential concepts of human population genetics that play an important role as risk factors. The molecular mechanisms involved in monogenic or multifactorial diseases are presented using specific examples. This also provides an opportunity to discover the new technological tools available (pan-genomic techniques, high-throughput genotyping, etc.) that are enabling major advances in this field. Finally, the module offers 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 topics are covered:

-Study of weight and thermal homeostasis in relation to a model of dysfunction: obesity. To this end, we will examine energy balance in terms of food intake and energy expenditure, comprising basal metabolism, physical activity, and adaptive thermogenesis (AT), and their respective regulation.

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

-Study of the different stages and physiological principles of breathing. Theoretical teaching will be supplemented by tutorials. Tutorials are based on document studies and the analysis of scientific articles in English. The choice of different scientific materials aims to show the interaction between the various topics covered and thus 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; facioscapulohumeral muscular dystrophy (FSHD). Facioscapulohumeral 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.

Functional Respiratory Testing: performing and interpreting respiratory tests in human pathology; spirometry: Level 1 and Level 2; pulmonary diffusion capacity; arterial blood gases; specific testing of respiratory muscles; 6-minute walk test; exercise testing; testing at high altitude.

Cardiovascular physiology:

Reminders about the anatomy of the heart: size, location, and orientation; the heart's outer layer; layers of the heart wall; chambers and large vessels of the heart; blood flow through the heart; heart valves; blood supply to the heart: coronary circulation; properties of heart muscle tissue.

Review of heart physiology: regulation of the basic rhythm; cardiac conduction system; modification of the basic rhythm: 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; vascular wall structure; blood pressure; vascular smooth muscle and vasomotor function; endothelial function.

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

How can vascular function be evaluated experimentally? Isolated artery loop model Cardiac Doppler ultrasound: a fabulous tool in 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; Cardioprotection 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: impedance measurement; DEXA (dual-energy X-ray absorptiometry); MRI; assessment of energy expenditure: calorimetry.

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The program offers refresher courses 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. Cellular addressing and trafficking: Ubiquitination and proteasome. Addressing to subcellular compartments, endocytosis and secretion pathways. The molecular basis of vesicular transport, budding, fusion, molecular motors. Signaling in membrane trafficking, genetic diseases related to trafficking, and hijacking by pathogens.

4. Cell cycle: Historical introduction. Molecular regulation of the cell cycle. The mitotic spindle, dynamics of microtubules and molecular motors, chromosome attachment mechanisms, checkpoints, regulation of mitosis exit and cytokinesis. Mitotic dysregulation 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. Physiopathological consequences of programmed cell death dysregulation.

Various study models are presented to introduce the importance of biological diversity in the discovery of cellular and molecular mechanisms, as well as in understanding 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, totipotency, pluripotency, 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 EU will first address the main communication pathways between normal cells and intracellular transduction pathways encountered in physiological and neurophysiological mechanisms. Thus, G protein-coupled receptors (GPCRs) will be studied, namely their structure, function, and modulation by interaction proteins involved in particular in the phenomenon of desensitization. The main intracellular pathways activated by membrane GCRs will be addressed (MAP kinase pathways, PI3 kinase, etc.).

Next, a significant portion of the course will focus on calcium signaling and Ca2+ homeostasis, Ca2+ being a ubiquitous signal in cellular signaling. Calcium homeostasis will be studied in particular during the response of lymphocytes after antigen 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 pathways of protection against oxidative stress will also be studied.The following chapter will address the endocannabinoid system, which will allow us to recap all the topics previously discussed in the course. The endocannabinoid system is responsible for multiple central and peripheral regulations.

Finally, two other topics will be addressed: the blood-brain barrier, which allows for highly integrated cellular communication between two environments, and the pancreatic β-cell, whose activity is crucial for regulating blood sugar levels through insulin secretion.

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

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Internship lasting more than four months in an organization (research laboratory, company, etc.) in France or abroad

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The physiology lab allows students to record cardiac action potentials in frog hearts using the intracellular microelectrode technique. This is a qualitative and quantitative method for measuring the electrical activity of the heart muscle.

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Cell culture is a basic technique in laboratories and is constantly evolving. It is important to understand its fundamentals, which are often poorly understood despite being an essential methodology in research and industry.

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Are you a third-year undergraduate or first-year master's student in Languedoc-Roussillon? Would you like to work in small groups with students from other programs on a project based on an unused scientific patent? Would you like to be supported and challenged by professional business creation coaches? Sign up for PEPITE Patent Project to present an innovative business creation project based on the exploitation of a real patent provided by a local research team that will open its doors to you!

Why?

-Because you can start your own business regardless of your field of study

-To be selected by an incubator-type support structure

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

What is the PEPITE Patent Project? A teaching unit consisting of key moments:

-a 3-day "tool training" seminar

-regular meetings with coaches

-deliverables to be submitted: summary note, market study, business plan

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

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The TER aims to prepare students to organize and carry out an in-depth bibliographic analysis that will enable them to approach their internship with knowledge of the state of the art in the field, in particular in order to produce a relevant and thoughtful introduction to their experimental work.

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