Translational Medicinal Chemistry

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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 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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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 Neuropsychopharmacology UE covers the molecular, cellular and integrated mechanisms underlying the mode of action of psychotropic drugs, using a number of pathologies as examples (depression, schizophrenia, anxiety, ....). The aim is to understand how the principles of pharmacology are specifically applied to mental disorders (e.g. pharmacodynamics, tolerance, physical and psychological dependence, etc.). Based on advances in neurobiological research and their application to drug therapy, the course aims to understand the concepts underlying the treatment of psychiatric disorders.

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This UE consists mainly of theoretical courses dealing with the molecular aspects of infectious diseases (bacteriology, virology, parasitology).

Bacteriology: The nature of infectious agents. Methods for studying pathogenesis (in vivo, in vitro, in silico and post-genomic study technologies) Strategies of pathogenic bacteria to survive in organisms: Bacterial adhesion to eukaryotic cells, antigenic variation and phase variation, invasion of non-phagocytic eukaryotic cells, mechanisms of resistance to phagocytosis, mechanisms of bacterial survival in phagocytic cells, membrane permeability management, bacterial secretion systems (types I, II, III, IV, V and VI), iron acquisition mechanisms, bacterial exotoxins, bacterial biofilms, examples of environmental regulation (thermoregulation, quorum sensing, etc.).).

Parasitology: Organization and cellular physiology of major pathogens in unicellular eukaryotic parasites (invasion and modification of the host cell; metabolic particularities and therapeutic targets); Genetics and molecular biology (genome organization, antigenic variation); Physiopathology and escape from the immune response.

Virology: Molecular mechanisms of the viral cycle; Expression of viral genomes; Transformation by viruses; Viral replication strategy; Plasticity of viral genomes; Structural importance of viruses in host interaction; 

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1) What is the genetic program underlying the development of the nervous system? This course highlights the type of decisions that gradually determine the neural destiny of cells and ensure their nervous function. The different stages considered are:

(i)the genesis of the nervous system

(ii)neuron specification

(iii)nerve function: axonal guidance and connectivity

(iv)neuronal remodeling

2) What molecular, cellular and environmental interactions control the development of the nervous system?

-Synaptogenesis and the major stages of development.

-The role of neurotrophic factors

-The role of electrical activity

-Critical periods

-The role of neuron-glial cell interactions.

-Neural stem cells

3) Developmental pathologies

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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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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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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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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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