L3 - Biochemistry

This course offers an in-depth study of the structural biochemistry of biomolecules, particularly proteins and nucleic acids.

The basic concepts and nomenclature used for analyzing 3D protein structures are briefly reviewed (Ramachandran diagram, structural motifs and domains, folding, family, superfamily, etc.). These concepts are supplemented by a study of the stability and dynamics of biomolecules.

The structural classification of proteins is detailed according to the four main types of folding. Structure-function relationships are illustrated using examples of proteins. The specific characteristics of membrane protein structures (integral proteins, membrane-bound proteins) are discussed.

The main tools for modeling and predicting secondary and tertiary structures are presented.

The different structures and functions of nucleic acids are studied. Protein-nucleic acid complexes are described from a structural point of view (main recognition motifs, etc.) and the concepts of recognition specificity are detailed.

This teaching is illustrated in tutorials. These tutorials consist of familiarizing students with the main databases used in structural biology, as well as with the PyMol software for analyzing 3D structures.

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This course provides fundamental knowledge in formal and structural enzymology.

- The first part of this course deals with formal kinetics (study of reaction rates, determination of the order of a reaction, equilibrium and kinetics, reversible and balanced reactions). The experimental aspects are presented in parallel (determination of kinetic constants by spectrophotometry, fluorescence, radioactivity, immunoassays, etc.).

- The second part of the course focuses on the study of single-substrate enzyme kinetics.

Definition of an enzyme, catalyst. Enzyme nomenclature (EC)

Michaelis kinetics. Michaelis-Menten equation. Definition of enzyme parameters,_KM, maximum velocity, catalytic constant, turnover. Different graphical representations (Lineweaer-Burk, Eadie-Hofstee). 

The different types of inhibition are also studied (competitive, noncompetitive, mixed) as well as their graphical representation.

Determination of inhibition constancy. Irreversible inhibitors.

Reaction rate. Arrhenius law.

- The third section focuses on describing multi-substrate enzyme kinetics from a formal perspective. With ternary complexes. Random or ordered mechanism.

Without ternary complex. Ping-Pong mechanism, Theorell-Chance. Cleland representation.

Graphical determination.

- The fourth part concerns equilibrium bonds and allostery.

Receptor-ligand/enzyme-substrate binding. Determination of the dissociation (or association) constant. Specific and non-specific binding.

Demonstration and graphical representation of Scatchard. Allosteric receptors (or enzymes). Non-Michaelian enzyme. Concept of cooperativity. Positive and negative cooperativity. Hill number, Hill graph.

Allosteric regulation models are presented. Allostery. Cooperative models: concerted (Monod-Wyman-Changeux) and sequential (Koshland-Nemethy-Filmer). Role of effectors, activators, or inhibitors. Example of hemoglobin and oxygen binding.

- The fifth part of the course links enzyme structures and their function using several examples. Description of the 3D structures and catalytic mechanisms of acetylcholinesterase, proteases, and nucleoside diphosphate kinase. Concept of catalytic triad, binding pocket, etc. 

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This course describes the methodology used by life science researchers to communicate the results of their experiments, both in writing and orally. As English is the common language of international researchers, a large part of this course is taught in English.

Written communication is addressed through the study of the (macro) structure of a research article and an examination of the publication process in scientific journals. Several elements of written structure (micro) are examined in order to understand the differences between scientific English and literary English: clarity, cohesion, and coherence.

These studies are supplemented by a supervised project during the semester, in which students are required to analyze a research article recently published in scientific literature and transcribe it in the form of an oral presentation (conference) in English.

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Molecular biology is not only a fascinating subject in its own right, but it also provides other biological disciplines (cell biology, genetics, physiology, etc.) with fantastic tools for modifying and quantifying genes and their products.

The EU is deepening its understanding of the mechanisms involved in the organization, maintenance, replication, and expression (transcription, post-transcriptional modifications, translation) of eukaryotic genomes.

In particular, we will explore the properties of information-carrying macromolecules (DNA, RNA, proteins) and how interactions between them explain the functioning of eukaryotic cells and their adaptation to the environment and the development of organisms.

At the same time, the main techniques used to monitor or modify gene expression, or to study the mechanisms of this expression, will be presented in lectures and explored in greater depth in tutorials through the analysis of results.

Thus, the tutorials address these topics in the form of (1) exercises that allow students to test their understanding of the knowledge described above, and (2) experiments taken from scientific articles for analysis. In this way, the fundamentals of scientific reasoning and critical analysis of results will be acquired and/or further developed.

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Functional genetics aims to better understand the relationships between genotype and phenotype. This course integrates the various aspects of gene and genome function analysis at the whole-genome level using in vivo approaches, as well as transcriptional regulation and regulation of eukaryotic genome expression. The course is illustrated with concrete examples in developmental genetics in physiological and pathological contexts.

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This course unit allows students to deepen their knowledge of metabolism. It provides a comprehensive overview of human metabolism, emphasizing the links between different metabolic pathways. It also shows how different tissues communicate to maintain overall energy homeostasis. Disruptions in this metabolism that cause certain diseases will be presented.

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This course builds on the Structural Biochemistry course in S5. Students will learn the basic concepts of the different approaches used for multi-scale structural characterization and the analysis of macromolecular interactions. The advantages and limitations of all the tools will be highlighted so that students can understand how they complement each other and know how to use them in an integrated way to answer a given biological question. 

The tutorials will be a mix of structural analysis using visualization tools (such as Pymol) and analysis of articles using a combination of the approaches studied in CM. Students will then be required to conceptualize their own experimental project to address a given problem.

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The course provides a comprehensive overview of the concepts required for mathematical modeling in biology. The focus is on linear and nonlinear dynamic systems in one and two dimensions. The course begins with essential concepts in linear algebra: matrices, systems of linear equations, geometric interpretation of the solutions to these systems as vectors and subspaces (line, plane, etc.). The theory of vectors and eigenvalues of matrices is introduced in relation to linear dynamic systems. For nonlinear dynamical systems, we present the qualitative theory of differential equations (attractors, phase portraits, zero-level isoclines) as an alternative to the often complicated calculation of solutions. The tutorial covers a large number of biological models used in ecology, epidemiology, oncology, and systems biology.

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This course unit allows students to consolidate and deepen their practical management of the large amount of experimental data obtained during a week of practical work in a block period (5 consecutive days). This data is obtained following the development of numerous different protocols, with a view to ensuring the best possible reproducibility of the preparations carried out and the fastest possible execution in the preparation, implementation, and analysis of the various experiments. A high degree of autonomy in the implementation of protocols will be encouraged, ultimately leading to experimental mastery and autonomy. These practical sessions also allow for group work (in pairs or threes, depending on capacity and numbers) and the writing of a report detailing the protocols carried out, all the experimental data obtained, and their analysis in order to determine a wide range of biochemical parameters. A significant part of the assessment will be based on the students' ability to generate, manage, exploit, and analyze raw experimental data with the utmost rigor.

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As part of this course, students will learn experimental principles based on the manipulation of nucleic acids. Lectures will focus on two main areas:

1. Implementation of molecular tools (cloning, nucleic acid analysis, vectorology) ii. Their applications (recombinant protein expression, genomic banking, transgenesis, CRISPR/CAS9 system, etc.) and reflection on the concept of ethics in biology.

The tutorials will consist of:

- Analysis of articles presenting issues to be resolved using the knowledge acquired in the course. The topics chosen will, as far as possible, refer to parallel L3 teaching units. These articles will be presented by students in the form of oral presentations by groups of 3 to 4 students to the whole class.

- Sessions reserved for the use of basic bioinformatics tools in the computer lab.

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This course unit aims, in both lecture and tutorial formats, to supplement the concepts of cell biology covered in L2 in BCM2 and BCM3 through the study of physiological and pathological conditions such as cancer.

These courses will introduce students to the importance of finding a suitable model system (cell lines or organisms for in vivo studies (Drosophila, C. elegans, zebrafish)) for answering a question and demonstrating a molecular mechanism.

The tutorials will enable students to work with advanced concepts in cell biology in conjunction with knowledge of the most commonly used methodologies in cell biology, such as flow cytometry, advanced fluorescence microscopy and electron microscopy techniques, proteomics, and knowledge of experimental models such as cultured cells, genetically modified and non-genetically modified animal models (C. elegans, zebrafish, transgenic mice, KO, KI, etc.). zebrafish, transgenic mice, KO, KI, etc.).

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Systems biology offers the possibility of understanding how living organisms function at different levels of their organization. This course will focus primarily on the subcellular level. At this level, systems biology models integrate several levels of interaction from the transcriptome, proteome, and metabolome. Predictions from in silico models can be used in biomedical research to understand multifactorial diseases and optimize drug treatments, in bioengineering to synthesize genomes with optimized properties and functions (synthetic biology), and to guide fundamental research on the principles of how living organisms function. The course includes a theoretical component (lectures and tutorials on gene, signaling, and metabolic network modeling) and a practical component (computer labs using Matlab software).

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The terms and conditions of this course unit are specifically tailored to the different L3 programs. However, the objectives are the same: to give students an overview of the professional world related to life sciences research.

Students will be offered a short internship in a laboratory/company or a supervised project with a tutor working in a laboratory or company associated with biology.

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