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:

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 aim of this course is to introduce functional genomics technologies and to present examples of biological questions that can be asked using them.

This unit aims to present "omics" functional genomics technologies, and some biological questions that they can address.The lectures are given by both associate professors and researchers.

Introduction to functional genomics: approaches, concepts and methods

An introduction to functional Genomics: approaches, concepts and methods

V. Coulon, UM / IGMM

Genome organization / Organisation des génomes

Techniques de séquençage / DNA sequencing methodsL. Journot, IGF

3D genome organization J. Poli, UM / IGH

Genome topological organisation and replication-V. Coulon, UM / IGMM

Régulation spatio-temporelle de l'expression des génomes / Spatio-temporal regulation of gene expressionTranscriptionEpissage / Splicing-V. Coulon, UM / IGMM

Non-coding RNAsV. Coulon, UM / IGMM

Interactomics / InteractomiqueIan Robbins, UM / IGMM

Proteomics and Pharmacogenomics / Protéomique et pharmacogénomiqueC. Bécamel, UM / IGF

Animal Models / Modèles animaux

Using Mice in Functional Genomics F. Poulat, IGH

La Drosophile en génomique fonctionnelle / Using Drosophila in Functional Genomics -F. Juge and S. Chambeyron, IGH

Scientificarticles analysis and presentation(15min + 10 min discussion per group of 3 students)

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The aim of the "Cellular Physiopathology and Cancer" course is to provide students with the knowledge necessary to follow the "Cancer Biology" course in M2. The course is organized in the form of a lecture with an introductory part followed by a part on current research in the laboratories. 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, mice...).Use of FLP/FRT, CRE-LOX, UAS-GAL4-GAL80, AttpP/B-PhiC31, CRISPR etc.

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

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

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

Genetic screens: genes with maternal effects and genes with zygotic effects.Cellular communication and signaling pathways: in the establishment of the dorso-ventral axis, in the formation of limbs, in the establishment of cell fate (some examples: Nervous system: lateral inhibition process ...).

-Segmentation: the gap, pair rule and segmental polarity genes.

Segmentation in invertebrates and somitogenesis in vertebrates, dynamic aspects (establishment and maintenance).

-Signaling and transcriptional networks

Transcriptional regulations during development, regulatory sequences during evolution, concept of gene networks. Transcriptional coupling and signaling pathways in cell fate

-The memory of transcriptional programs by epigenetic mechanisms:

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

Involvement of epigenetic mechanisms during cell differentiation

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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 neuropsychopharmacology course deals with the molecular, cellular and integrated mechanisms underlying the mode of action of psychotropic drugs, using a few pathologies as examples (depression, schizophrenia, anxiety, ....). It aims to understand how the principles of pharmacology are specifically declined in the context of psychological disorders (e.g. pharmacodynamics, tolerance, physical and psychic dependence,...). Based on the advances in neurobiology research and their therapeutic applications in medication, the course aims to understand the concepts underlying the treatment of psychiatric disorders.

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This UE is mainly composed of theoretical courses dealing with molecular aspects of infectious diseases (bacteriology, virology, parasitology)

Bacteriology: The nature of infectious agents. Methods of 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 survival of bacteria in phagocytic cells, management of membrane permeability, bacterial secretion systems (type I, II, III, IV, V, and VI), mechanisms of iron acquisition, bacterial exotoxins, bacterial biofilms, examples of environmental regulations (Thermo-regulation, Quorum sensing...)).

Parasitology: Organization and cellular physiology of major pathogens in parasitic unicellular eukaryotes (invasion and modification of the host cell; metabolic characteristics 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 progressively specify the neural fate of cells and ensure their nervous function. The different steps considered are:

(i) the genesis of the nervous system

(ii) the specification of neurons

(iii) nerve function: axonal guidance and connectivity

(iv) neuronal remodeling

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

-Synaptogenesis and major developmental milestones.

-Roles of neurotrophic factors

-Roles of electrical activity

-Critical periods

-Roles of neuron-glial cell interactions.

-Neuronal 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; 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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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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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 teaching is carried out by teacher-researchers from the UFRs of medicine, science and pharmacy. It is organized into 42 hours of classes and supervised work divided into 7 themes (see Syllabus) including 2 series of article presentations; the first series on articles proposed by the speakers of each theme. A second series on articles chosen by the students. The students organize a mini-colloquium at the end of the course where the articles are presented. They write short reports of these articles for the Medecine-Sciences magazine.

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