Translational Medicinal Chemistry

The program offers a refresher course and an in-depth study of the major concepts and methodologies of cell biology, organized around various themes:

1. Cytoskeleton: Introduction to the different types of cytoskeletons. Polymerization properties of actin and tubulin. Proteins associated with the cytoskeleton that regulate 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 trafficking and targeting: Ubiquitination and the proteasome. Targeting to subcellular compartments; endocytosis and secretion pathways. The molecular basis of vesicular transport: budding, fusion, and molecular motors. Signaling in membrane trafficking; genetic diseases associated with trafficking; and hijacking by pathogens.

4. Cell Cycle: Historical Overview. Molecular Regulation of the Cell Cycle. The mitotic spindle, microtubule dynamics and molecular motors, mechanisms of chromosome attachment, checkpoints, regulation of mitotic exit, and cytokinesis. Mitotic abnormalities 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. Pathophysiological consequences of dysregulation of programmed cell death.

Various research models are presented to highlight the importance of biological diversity in the discovery of cellular and molecular mechanisms, as well as in the understanding of human diseases.

The program offers a review of key concepts 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 involved in 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 regulation during development and pathogenesis. Regulation by signaling pathways. Mechanotransduction.

3. Addressing and cell traffic: Ubiquitination and the proteasome. Transport to subcellular compartments, endocytosis, and secretion pathways. The molecular basis of vesicular transport, budding, fusion, and molecular motors. Signaling in membrane trafficking, genetic diseases linked to trafficking, and disruption 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 mitotic 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 mechanisms of apoptosis; signaling pathways involved. Role in maintaining homeostasis. Pathophysiological consequences of dysregulation of programmed cell death.

Various study models are presented to highlight the importance of biological diversity in the discovery of cellular and molecular mechanisms, as well as in the understanding of human diseases.

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The “Cellular Pathophysiology and Cancer” course unit aims to provide students with the knowledge necessary to pursue the “Cancer Biology” track in the M2 program. The course unit is organized as a lecture, consisting of an introductory section followed by a section on current research in the laboratories. Students are required to give an oral presentation on a scientific article (usually in pairs).

The goal of the cellular pathophysiology and cancer course is to provide the scientific background necessary to succeed in the M2 program in cancer biology. Each lecture is structured as a seminar, beginning with a general introduction to the field and followed by a more specialized focus on research conducted in laboratories. Students are required to prepare an oral presentation based on the analysis of a scientific article (usually in pairs).

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-A General Introduction to Developmental Biology

How do cells build a multicellular animal organism from a single genome? The genotype-phenotype relationship.

-Genetic Testing Reminders

Nature of mutations (loss-of-function; gain-of-function), the concept of a “master gene,” clonal analysis (generation of somatic or germline clones), the concept of cellular autonomy....

-Genetic models and methods.

Study of regulatory regions, establishment of transgenic lines, enhancer traps, reporter genes (GFP, mCherry, etc.), model organisms (Drosophila, C. elegans, mice, etc.).Use of FLP/FRT, CRE-LOX, UAS-GAL4-GAL80, AttpP/B-PhiC31, CRISPR, and other systems

-Positional information, genes with maternal effects, and the establishment of asymmetry.

Models and Mechanisms of Positional Information = induction, Spemann and Mangold’s experiment, organizing centers, the concept of morphogens in invertebrates and vertebrates

-Defining the axes: anteroposterior, dorsoventral.

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

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

Segmentation in invertebrates and somite formation in vertebrates: dynamic aspects (establishment and maintenance).

-Signaling and transcriptional networks

Transcriptional regulation during development, regulatory sequences throughout evolution, and the concept of gene networks. The interplay between transcription and signaling pathways in cell fate

-Transcriptional program memory via epigenetic mechanisms:

Hox homeotic genes and segmental identity. Concepts in Evo-Devo. The Polycomb and Trithorax complexes.

The Role of Epigenetic Mechanisms in Cell Differentiation

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Behaviors—whether determined by conscious or unconscious processes—are based on complex neurobiological substrates. They are, in fact, 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 its species.

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

-Gene–Behavior

The Relationship Between Genotype and Phenotype—Environmental Impact—Attention 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 Bases of Emotions - Functions of Emotions - Maladaptation: Pathological Aspects: Emotional Disorders

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The Neuropsychopharmacology course covers the molecular, cellular, and integrated mechanisms underlying the mode of action of psychotropic drugs, using several disorders (depression, schizophrenia, anxiety, etc.) as examples. It aims to understand how the principles of pharmacology apply specifically to mental disorders (e.g., pharmacodynamics, tolerance, physical and psychological dependence, etc.). Drawing on advances in neurobiological research and their therapeutic applications in medication, the course aims to provide an understanding of the concepts underlying the treatment of psychiatric disorders.

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This course unit consists primarily of lectures covering 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 research technologies) Strategies of pathogenic bacteria for survival within hosts: 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 within phagocytic cells, regulation of membrane permeability, 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 within parasitic unicellular eukaryotes (invasion and modification of the host cell; metabolic characteristics and therapeutic targets); Genetics and Molecular Biology (genome organization, antigenic variation); Pathophysiology and evasion of the immune response

Virology: Molecular mechanisms of the viral life cycle; Expression of viral genomes; Viral transformation; Viral replication strategies; Plasticity of viral genomes; Structural significance of viruses in host-virus interactions; 

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1) What is the genetic program underlying the development of the nervous system? This course highlights the types of decisions that progressively determine the neural fate of cells and ensure their nervous function. The various stages considered are:

(i) the development of the nervous system

(ii) the specification of neurons

(iii) nervous 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.

-Roles of neurotrophic factors

-Functions of electrical activity

-Critical periods

-Roles of neuron-glial cell interactions.

-Neural stem cells

3) Developmental Disorders

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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; facioscapiohumeral muscular dystrophy (FSHD). Facioscapiohumeral muscular dystrophy (FSHD): zebrafish model; mouse model; cellular models; clinical trials.

Respiratory Physiology:

Respiratory Physiology: Anatomy of the respiratory system; the mechanism of respiration; gas exchange; transport of respiratory gases in the blood; regulation of respiration

Respiratory Assessment in Small Animals: Why Assess Respiratory Function in Small Animals? Plethysmography; in vitro contractile force.

Functional Respiratory Tests: performance and interpretation of respiratory tests in human medicine; spirometry: Level 1 and Level 2; pulmonary diffusion capacity; arterial blood gases; specific tests of the respiratory muscles; 6-minute walk test; exercise testing; tests involving exposure to high altitude.

Cardiovascular Physiology:

Review of cardiac anatomy: size, location, and orientation; the heart’s envelope; the layers of the heart wall; the heart’s chambers and major vessels; the flow of blood through the heart; cardiac valves; blood supply to the heart: coronary circulation; properties of cardiac muscle tissue.

Review of cardiac physiology: regulation of the baseline heart rate; the cardiac conduction system; changes in the baseline heart rate: 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; structure of the vascular wall; blood pressure; vascular smooth muscle and vasomotor function; endothelial function.

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

How can vascular function be assessed experimentally? Isolated arterial ring model; Cardiac Doppler ultrasound: a powerful 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; perfused isolated heart (Langendorf); Isolated cardiomyocytes; Cardioprotection techniques.

Endocrinology: Weight Balance

Description of eating behavior; Energy balance; Central regulatory structures of food intake; Regulatory mechanisms of food intake; Factors modulating appetite and food intake; Nutritional assessment; Eating disorders; Functional assessment: impedance measurement; DEXA (dual-energy X-ray absorptiometry); MRI; Assessment of energy expenditure: calorimetry.

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The EU will first address the main communication pathways between normal cells and intracellular signal transduction pathways encountered in physiological and neurophysiological mechanisms. Thus, G protein-coupled receptors (GPCRs) will be studied, specifically their structure, function, and modulation by interacting proteins involved, in particular, in the phenomenon of desensitization. The main intracellular pathways activated by membrane-bound GPCRs will be discussed (MAP kinase pathways, PI3 kinase, etc.).

Next, a significant portion of the course will focus on calcium signaling and Ca²⁺ homeostasis, as Ca²⁺ is a ubiquitous signal in cellular signaling. Calcium homeostasis will be studied in particular in the context of the lymphocyte response following antigenic 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 protective mechanisms against oxidative stress will also be examined.The following chapter will address the endocannabinoid system, which serves to summarize all the topics previously covered in the course. The endocannabinoid system is responsible for numerous central and peripheral regulatory processes.

Finally, two other topics will be covered: the blood-brain barrier, which provides a framework for discussing cellular communication in a highly integrated manner between two environments, and the pancreatic β-cell, whose activity is crucial for regulating blood glucose levels through insulin secretion.

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An internship lasting more than 4 months at an organization (research laboratory, company, etc.) in France or abroad

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The physiology lab course allows students to record cardiac action potentials in a frog’s heart 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 fundamental technique in laboratories and is constantly evolving. It is important to understand its basics, which are often poorly understood, even though it is an essential methodology not only in research but also in industry.

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Are you a third-year undergraduate or first-year graduate student in the Languedoc-Roussillon region? Would you like to work in small groups with students from other programs on a project-based approach, using an unused scientific patent? Would you like to be guided and challenged by professional startup coaches? Sign up for the PEPITE Patent Project to present a plan for an innovative startup based on the commercialization of a real patent provided by a local research team that will welcome you with open arms!

Why?

-Because you can start your own business no matter what field you're in

-To be selected by an incubator-type support organization

-To help you build a network in the fields of entrepreneurship and innovation

PEPITE Patent Project—what is it? A teaching unit consisting of key activities:

- a 3-day "tool training" seminar

-regular meetings with the coaches

-Deliverables to be submitted: summary report, market research, business plan

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

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The course is taught by faculty members from the departments of medicine, science, and pharmacy. It consists of 42 hours of lectures and supervised work divided into 7 themes (see Syllabus), including two series of article presentations: the first series focuses on articles selected by the instructors for each theme, and the second series features articles chosen by the students. At the end of each course unit, students organize a mini-symposium where the articles are presented. They write abstracts of these articles for the journal *Medecine-Sciences*.

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