STATE DOCTORATE IN PHARMACY

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2 credits of your choice

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This course unit aims to reinforce and illustrate the knowledge acquired in the course unit “Molecular Bases of Infectious Diseases” through the analysis of scientific publications on topics in infectious diseases. Publications employing a variety of molecular and cellular approaches in bacteriology, parasitology, and virology—ranging from the most traditional to the most recent—are analyzed with the students.

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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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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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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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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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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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The GIS Practice course consists of training in the use of Geographic Information Systems, covering basic concepts related to geographic information and proficiency in the open-source software QGIS. The majority of the course is devoted to an introduction through a combination of lectures and hands-on exercises. A personalized capstone mapping project allows students, at the end of the course, to apply the concepts they have learned. An introductory lecture by industry professionals provides context for the relevance of GIS approaches in general hydrology.

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The overall objective of this course unit is to deepen students’ understanding of the concepts necessary for studying symbiotic interactions, whether parasitic or mutualistic. To this end, we will examine both the specific characteristics and the ubiquity of the parasitic lifestyle across the tree of life. We will discuss the defense mechanisms of host organisms, the concepts of favoring and manipulation, the consequences of host-symbiont interactions on life history traits, and the influence of these interactions on the diversification of organisms.

The lab sessions will provide an opportunity to explore these concepts in greater depth using examples of major interactions involving symbionts (viruses, bacteria, and unicellular and multicellular eukaryotes) and a variety of hosts (both unicellular and multicellular).

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This course unit aims to reinforce and illustrate the knowledge acquired in the course unit “Molecular Bases of Infectious Diseases” through the analysis of scientific publications on topics in infectious diseases. Publications employing a variety of molecular and cellular approaches in bacteriology, parasitology, and virology—ranging from the most traditional to the most recent—are analyzed with the students.

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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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Optimized management and protection of water resources (both surface and groundwater) require consideration of water quality. The assessment of the qualitative status of water bodies—particularly in light of current legislative frameworks—is based on specific chemical and microbiological quality criteria, as well as standards tailored to the intended uses of these resources.

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This course is shared among MI students in the Master’s in Chemistry program: ICAP P1, ICAP P2, MAT P1, MAT P2, and BM (second semester). The following topics will be covered:

• The 12 Principles of Green Chemistry and Units of Measurement in Green Chemistry;
• Synthesis Strategies in Sustainable Chemistry;
• Alternative or environmentally friendly solvents for synthesis and extraction;
• Unconventional Activation Techniques and Applications.

CM: 13

TD: 7 H

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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 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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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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In the field of bioprocess engineering, an understanding of the metabolism of catalysts (cells, microorganisms) is essential. This research unit will focus on characterizing the diversity of valuable microbial metabolites (primary and secondary metabolites) and the bioprocesses that utilize these microorganisms to produce these molecules.

This course unit includes interactive lectures, tutorials, and practical exercises (lab work in the computer lab + independent project-based work in small groups).

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Proteins are now widely used as therapeutic tools in human and animal health. An understanding of the pathways involved in peptide and protein synthesis, their folding, and any post-translational modifications is essential before considering the biosynthesis of any therapeutic protein. Methods for better characterizing these proteins are also essential to ensure the quality of the proteins produced for therapeutic or industrial use. Methods of protein engineering designed to improve their original properties will also be discussed.

The EU program includes lectures and seminars led by faculty members and researchers.

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NMR:

Liquid-phase NMR (Nuclear Magnetic Resonance) is an essential spectroscopic analytical method for chemists, enabling, in particular, the determination of the structure of small organic molecules or macromolecules in solution, as well as the study of dynamic phenomena... The objective of this course unit is to understand the phenomena involved in this technique and to relate them to the various structural insights provided by this method. The goal is to be able to interpret the spectral data obtained from this analysis to elucidate the structure and stereochemistry of organic molecules or the structures of polymers, or to monitor reactions.

X-ray diffraction:

X-ray diffraction is a powerful, non-destructive technique for characterizing the crystalline structure of materials; it is also capable of providing crystallographic and structural information, such as lattice parameters and atomic positions. This includes all crystalline materials, such as ceramics, materials for energy and information storage and processing, as well as organic molecules and metal complexes (interatomic distances and angles, stereochemistry (chirality, stereoisomerism, etc.), intra- and intermolecular bonds, etc.). The objective of this course unit is to provide an introduction to crystallography and diffraction, with the goal of understanding the operation and characteristics of an X-ray diffractometer, as well as interpreting diffraction patterns (structural analysis, lattice parameters).

Hourly volumes*:

            CM: 10

            TD: 10

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Knowledge of gas chromatography and mass spectrometry techniques using electron impact ionization and a quadrupole mass analyzer for the analysis of volatile organic molecules.

1) GC-MS analyses of volatile organic compounds:

• Electron Impact (EI) Ionization Techniques
• Chemical Ionization (CI) Techniques
• Quadrupole (Q) Analysis Techniques
• GC/MS Couplings

2) Applications in organic chemistry analysis and the characterization of volatile samples.

Hourly Volumes*:

CM: 3:00 p.m.

TD: 5 hours

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The course on medicinal chemistry aims to introduce students to the key steps in the process of developing molecules with biological activity. In particular, the course will cover the interactions involved, the concept of the pharmacophore, bioisostery, and other related topics, as well as structure-activity relationship studies, enabling students to consider appropriate strategies and structural modifications.

Hourly volumes*:

CM: 3:00 p.m.

TD: 5 hours

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This course unit is organized into the following activities: Getting Started—The R Environment; Structures in R; Input and Output in R; Manipulating Structures in R; Fundamentals of Algorithms; Programming Structures in R; Group Mini-Project: Creating an R function to address a real-world “water” problem

Objectives*:

The course aims to 1) introduce the basics of the interpreted language used in engineering tools (environment, structures, input/output, structure manipulation, graphics, programming), 2) to provide the fundamental theoretical knowledge needed to create their own functions and programs using practical examples in water sciences so that 3) students can independently continue their self-directed learning and develop expertise in R.

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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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Knowledge of the latest mass spectrometry techniques for the qualitative analysis of organic molecules and biomolecules.

1) Description of the fundamental principles (Ion Science and Technology):

- Ionization Techniques

- Analytical Techniques

- Tandem mass spectrometry (MS/MS)

- LC/MS and LC/MS/MS couplings

2) Application in the analysis of biomolecules and the monitoring of organic chemical reactions.

Hourly Volumes*:

CM: 3:00 p.m.

TD: 5 hours

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The purpose of this course is to teach liquid-phase chromatography and gas-phase chromatography.

Hourly volumes*:

            CM: 3:00 p.m.

            TD: 5 hours

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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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In the field of biotechnology, bioprocesses involve the industrial application of biological tools (such as enzymes, microorganisms, or cells derived from higher organisms) for the synthesis of products of interest. In this course unit (UE), the focus will be on the use of microbial and cellular catalysts. Products of interest may include, for example, fermented foods (wine, beer, etc.), energy molecules (bioethanol, methane, etc.), chemical intermediates, or biopharmaceuticals (vaccines, monoclonal antibodies, growth factors, etc.). The knowledge, skills, and competencies acquired during this course unit will be applicable to any sector of the biotechnology industry. The examples provided will correspond to the career paths targeted by both degree programs (the Agrosciences and Health tracks).

This course will focus on bioprocesses and the environment in which the biological reaction takes place (the bioreactor). The course will also address the description and modeling of biological reactions, including a presentation of the approach used in bioprocess engineering. The remainder of the course will be devoted to applying this approach to reactors operated in batch mode (or discontinuous culture). Other operating modes will be covered in the M2 HAV930V course, “Bioprocess Engineering—Continuous and Fed-Batch.”

This course unit includes interactive lectures, tutorials, and practical exercises (lab sessions in the computer lab + independent project-based work in small groups).

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