CHOICE 1

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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-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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Three main themes are addressed:

-Study of weight and thermal homeostasis in relation to a model of dysfunction: obesity. For this purpose, the energy balance with food intake and energy expenditure composed of basic metabolism, physical activity and adaptive thermogenesis (AT) and their respective regulation will be addressed.

-Study of biological rhythms, through the description of the nature and properties of biological rhythms (ultradian, circadian and infradian), the description of endogenous circadian oscillators, and the detailed presentation of the molecular mechanisms of circadian clocks.

-Study of the different stages and physiological principles of breathing. Theoretical lessons will be complemented by tutorials. The tutorials are based on document studies and the analysis of scientific articles in English. The choice of the various scientific supports aims at showing the interaction of the various approached topics and thus the concept of integrative physiology.

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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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This EU aims to provide a broad overview of emerging quantitative interdisciplinary fields in bioscience, ranging from advanced experimental techniques in microscopy and synthetic biology, to systems approaches.

In an innovative way, these methodological aspects will be presented in the context of biological and biophysical concepts such as robustness and optimality of biological systems, gene regulation and the fundamental principles underlying membrane and genome organization.

The main topics will be introduced first with traditional lectures and will be developed through individual or team projects where students will learn to apply specific techniques through examples, and see how these can be used to explore specific biological questions. These projects will involve literature reviews, use of existing code, or development of new code (depending on the student's experience) and will constitute half of the final assessment.

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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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