Master's Degree in Translational Medicinal Chemistry

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 "Cellular Physiopathology and Cancer" course aims to provide students with the knowledge necessary to follow the "Cancer Biology" program in M2. The course is organized in the form of a conference with an introductory section followed by a section on current research in laboratories. Students are required to give an oral presentation on a scientific article (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 to 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 pairs).

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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 testing reminders

Nature of mutations (loss-of-function; gain-of-function), concept of "master gene," clonal analysis (generation of somatic or germline clones), 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, etc. 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, concept of morphogens in invertebrates and vertebrates

-Establishment of axes: anteroposterior, dorsoventral.

Genetic screens: genes with maternal effects and genes with zygotic effects. Cell communication and signaling pathways: in establishing the dorsoventral axis, in limb formation, in establishing cell fate (some examples: nervous system: lateral inhibition process, etc.).

-Segmentation: gap genes, pair rule genes, and segmental 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, concept of gene networks. Coupling of transcription and signaling pathways in cell fate.

-Transcriptional program memory through epigenetic mechanisms:

Hox homeotic genes and segmental identity. Concepts of Evo-Devo. 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 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 neuropsychopharmacology EU deals with the molecular, cellular, and integrated mechanisms underlying the mode of action of psychotropic drugs, using a few pathologies (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.). Based on 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 course consists mainly of theoretical lectures 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 technologies) Strategies used by pathogenic bacteria to survive in organisms: Adhesion of bacteria 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, management 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: Cellular organization and 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 immune response evasion

Virology: Molecular mechanisms of the viral cycle; Expression of viral genomes; Transformation by viruses; Virus replication strategies; Plasticity of viral genomes; Structural importance of viruses in host interactions; 

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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 fate of cells and ensure their nervous function. The different stages considered are:

(i) the genesis of the nervous system

(ii) the specification of neurons

(iii)nerve function: axonal guidance and connectivity

(iv) neural 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

-Roles 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; 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 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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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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Teaching is carried out by lecturers and researchers from the medical, science, and pharmacy departments. It consists of 42 hours of lectures and supervised work divided into seven themes (see Syllabus), including two series of article presentations: the first series on articles proposed by the lecturers for each theme covered, and the second series on articles chosen by the students. Students organize a mini-symposium at the end of the course where the articles are presented. They write summaries of these articles for the journal Medecine-Sciences.

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