M2 Gene Cell Development

Sophie Dupré, MCU CN, UPSay Frédéric Coquelle MCU HC, UPSay.

This course will be running for one-week full time. Each new concept will be immediately put into practice on concrete examples using computers and ImageJ and Fiji software. Active learning methodology (Jean Piaget, John Dewey and Kurt Lewin) by combining maieutic educational methods, and debate (Oscar Brenifier) and spiral learning (J.C. Bruner).

Acquisition of skills allowing the student to correctly visualize and interpret biological images and to get quantitative data. Task automation by using ImageJ macro language.

1/ Describe and explain theoretical bases for digital image interpretation: Digital image, image formats, spatial sampling, convolution functions and deconvolution, periodical and non-periodical signals, filters, quantification (segmentation, granulometry, contrasts calculation, signal to noise ratio determination, theory of image correlation, statistical approaches for co-localization analysis, Fourier analysis).

2/ Explain basic principles of 3D reconstruction: images combination, retroprojection methods, iterative methods.

3/ Use ImageJ (Fiji) handling to perform channels splitting and merging, segmentation by thresholding, granulometry, quantification on protein gels and microscopy images, déconvolution, intra-cellular co-localization, filters, getting periodical signals, projections simulation, 3D reconstruction from projected data, macro language programming including user interface, 3D rendering.

4/ Master the scientific argumentation (proofs versus viewpoints: reasoning, facts, examples).

Digital Image Processing, W. Burger and M.J. Burge, Springer (2nd Edition).

Octobre.

ORSAY

Marie-hélène Cuif, Pr UPSay, marie-helene.cuif@universite-paris-saclay.fr Isabelle Guénal, Pr UVSQ, Isabelle.guenal@uvsq.fr Bernard Mignotte, Pr UVSQ, bernard.mignotte@uvsq.fr Simon Saule, Pr UPSay, simon.saule@curie.fr.

The course contains conferences allowing for the discovery of specific problematics and approaches in the field of cell biology. The exam consists in a oral presentation. Publications proposed by each speaker are available several weeks before the course starts. Each student selects one of the publications at the beginning of the week of courses. The students will have the opportunity of a direct contact with the speaker to get answers to their questions.

Course content :
Series of lectures on various aspects of cellular dynamics and signaling pathways regulating cell polarity, survival, growth and division. Conferences are given by researchers and academic specialists from internationally recognized teams based nearby.

Conference themes:
-Mitochondrial dynamics and cell behavior
-Cell survival and cell signaling cross talk
-Signaling and tumor progression
-Oocyte dynamics and mechanics
-Microtubule dynamics mechanisms, regulation and therapeutic targets
-Molecular basis of actin dynamics
-Architecture and function of primary cilia from paramecy to human pathologies

Intended learning outcomes:
At the end of the course the student should be able to:
Awareness to the issues and methods in current cell biology.
question scientific data and suggested experiments to answer a problematic linked to the attended conferences
Ability to analyze a scientific paper, synthesize and present results.

The prerequisites for this course are similar as the ones for the whole curriculum Gene Cell Development: the course is opened to students holding a Master 1 year, with very strong background in cell biology, genetics, epigenetics.

Basic concepts of cell biology can be consulted in "Molecular Biology of the Cell" from Bruce Alberts et al.

Novembre.

ORSAY - VERSAILLES

UPSay - Emmanuel CULETTO Emmanuel.CULETTO@i2bc.paris-saclay.fr Anne-Hélène MONSORO-BURQ anne-helene.monsoro-burq@curie.fr Laurent THEODORELaurent.Theodore@universite-paris-saclay.fr? Patricia UGUENpatricia.uguen@universite-paris-saclay.fr

UVSQ - Isabelle GUENAL isabelle.guenal@uvsq.fr Anne-Marie PRET anne-marie.pret@i2bc.paris-saclay.fr Sébastien SZUPLEWSKIsebastien.szuplewski@uvsq.fr?.

The students will attend 2 or 3 conferences per day over a period of a week given by scientists who are experts in each domain covered. They will keep a logbook in the form of a table on line in which they will present the most important points of each conference and what questions remain unanswered. Each student will choose one theme developed during the conferences for which the speaker will provide a review and a scientific article. They will use these resources to present the background context of the theme, a question that remains unanswered and propose how to proceed experimentally to answer the question during a discussion with a jury.

The general goal of this course is to provide insights into specific issues in Development: What are the mechanisms underlying the processes of metazoan morphogenesis and differentiation? What are the advantages of the diverse model systems? What are the methods and approaches used?
The titles of the conferences are the following (though some of these may change from one year to the next) :
- Subcellular Polarization of mRNAs
- The Molecular Basis of the Circadian Rhythm Clock
- Cell Fitness and Competition
- Regulation of Growth and Metabolism
- Determination of final organ and organismal size
- Stochastic Cell Specification and Maintenance
- Autophagy and Development
- Neural Crest Cell Specification
- miRNAs and Development
- Cell Reprogramming.

Solid Bachelor's level in Genetics, Cell Biology and Development.

The following reviews cover themes presented during the course: Okamoto et al. 2013 A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila. Genes and Dev. 27:87 Dubowy and Sehgal 2017 Circadian Rhythms and Sleep in Drosophila melanogaster. Genetics 205:1373 Savini and Wang (2019) Does Autophagy Promote Longevity? It Depends. Cell 177:221 Yagi et al. (2017) Epigenetic foundations of pluripotent stem cells that recapitulate in vivo pluripotency. Lab. Invest. 00:1 Prasad et al. (2012) Induction of the neural crest state: Control of stem cell attributes

Octobre.

GIF-SUR-YVETTE

Sébastien BLOYER (PU UPSay I2BC) Benoit MOINDROT (MCU UPSay I2BC) Sophie NETTER (MCU UVSQ I2BC) conférenciers invités.

This course is organized as a 1-week scientific symposium, with lectures/conferences held by invited speakers. During the conference, a group of 3-4 students will play the role of ‘chairman’: They will be ask to (1) introduce the invited speaker, (2) provide a general introduction of the research area that will later be extensively developed by the invited speaker, (3) lead the discussion and animate the debate between the speaker and the audience. Thus, besides new scientific knowledge acquired during the lectures, the students will acquire and develop know-hows in synthetic presentation of a new topic, public speaking and animation with the audience. The student will be evaluated based on their active implication during the course, and based on their ability to present, using a few experiments from research articles, an epigenetic phenomenon that has not been covered during the course [oral exam].

This course is organized as a scientific symposium, with lectures held by invited researchers expert in the field of epigenetics, epigenomics and/or non-coding RNAs.
Many aspects of epigenetic processes and phenomena will be covered, such as the control of gene expression, genomic imprinting, X chromosome inactivation, stem cells pluripotency, epigenetic memory and reprogramming, in connection with environmental and/or epigenetic diseases.
The recent advances in cancer single cell epigenomics and 3D genome organization will also be addressed. The focus will be laid on the implication of non-coding RNAs in epigenetic mechanisms, and more particularly in the inter- and trans-generational inheritances of the epigenetic information.

At the end of this course, the students should be able to:
(1) Name, describe and discuss the role of non-coding RNAs in the trans- generational inheritance of the epigenetic information and the different epigenetics layers impacting on cell/tissue identity.
(2) Analyze and interpret epigenetic and epigenomic data from research articles and reviews
(3) Deliver a concise, informative and structured presentation on an epigenetic phenomenon.

M1 levels in genetics, genomics and molecular biology. In addition, notions of high-throughput sequencing methods and epigenetic mechanisms developed in the Master 1 core course and/or several Master 1 teaching units (Epigenetics, Controle of gene expression, ‘génomique fonctionnelle’, ‘analyse et valorisation de données « omiques »’,…) should be understood and comprehended.

Books available at Paris Saclay libraries: - Epigenetics by C. David Allis, Marie-Laure Caparros, Thomas Jenuwein and Danny Reinberg - Epigenetics, Nuclear Organization and Gene Function with Implications of Epigenetic Regulation and Genetic Architecture for Human Development and Health by Lucchesi and John C.

Web links : - EpiGensSys European Network Website: http://www.epigenesys.eu/fr/ - Edith Heard’s lectures at the Collège de France (in French): https://www.college-de-france.fr/site/en-edith-heard/_course.htm.

ORSAY - GIF-SUR-YVETTE

Caroline Borday, MCU PSUD, CNU 65 Frédéric Coquelle MCU PSUD, CNU 65 Marianne Malartre MCU PSUD, CNU 65 Anne-Hélène Monsoro-Burq PR PSUD, CNU 65 Patrick Pla MCU PSUD, CNU 65 Simon Saule PR PSUD, CNU 65 Marie-Noelle Soler CNRS.

This practical course has 2 weeks of full-time manipulations, which allows students to approach different experimental specialties: - In vivo experimental embryology and molecular embryology: microinjection in the Xenopus laevis embryo, chicken embryo retinal dissection, whole mount in situ hybridization. - Cell culture: primary culture of retinal pigmented epithelium of chicken embryos, uveal melanoma cell culture, transfection - Molecular biology: antisense RNA synthesis - Microscopy and image analysis: taking pictures with a stereomicroscope for the study of whole mount embryos; optical microscopy (interference contrast or epifluorescence); initiation to confocal microscopy; videomicroscopy; image analysis on advanced imaging platform (ImageJ)

The course takes place in the Cellular Biology classrooms of Paris Sud University and on the RIO imaging platform and conference spaces of the Curie Institute (Building 110-111, Orsay).

This practical course provides hands-on experiments to address the roles of signaling pathways involved in animal and cancer development both in vivo and in vitro. Three mini-research projects are conducted that allow students to appreciate the reality of research, its possibilities and its current limitations: examples of last years projects:
1- The impact of the BRafV600 mutation, a frequent cause of cutaneous melanoma, in the course of development in the melanocyte lineage in Xenopus laevis.
2- The study of intracellular trafficking of melanosomes, cytoplasmic organelles transporting melanin within the pigment cells in primary cultures of chick RPE cells and to study the role of cytoskeleton in this process.
3- PRL3 is upregulated in aggressive uveal melanoma that produce metastasis. The aim of the third project is to quantify the effect of PRL3 on uveal melanoma cell migration and to know if Mitf, the main differentiation factor of melanocytic lineage, is able to counteract (or enhance) this effect.

Intended learning outcomes
•To acquire an overview of current challenges for basic and translational research in the field of cell biology, development and cancer.
•To design an experimental methodology.
•To perform several experiments in parallel, over several days by following several protocols.
•To guarantee research experimental protocols and results traceability by writing rigorously a laboratory notebook.
•To describe, analyze and interpret obtained data in a publication format and an oral presentation.

The prerequisites for this course are similar as the ones for the whole curriculum Gene Cell Development: the course is opened to students holding a Master 1 year, with very strong background in cell biology, genetics, epigenetics. Knowledge in developmental and stem cells biology will be useful, but is not required.

Basic concepts of developmental genetics can be consulted in "Developmental Biology" from Scott F. Gilbert (Eleventh Edition) or in "Principles of Development" by Lewis Wolpert (Oxford University Press).

A specific review is: Melanocytes in Development, Regeneration, and Cancer- White RM and Zon LI – Cell Stem Cell. 2008 Sep 11;3(3):242-52. doi: 10.1016/j.stem.2008.08.005.

Septembre - Octobre.

ORSAY

Monsoro-Burq Anne-Hélène, anne-helene.monsoro-burq@curie.fr Pla Patrick, patrick.pla@curie.fr Saule Simon, simon.saule @curie.fr Borday Caroline, caroline.borday@universite-paris-saclay.fr Coquelle Frédéric, frederic.coquelle@curie.fr.

This course is organized as a four days colloquium, followed by oral defense from students the next week. The colloquium is also opened to Ph.D. students, postdoctoral fellows and researchers, to stimulate vivid scientific interactions. Several types of discussions take place: during the seminars, during poster sessions, with round tables on academic and industrial careers, and other events. Poster Prize is awarded. Travel awards are available.

Course content :
These seminars mobilize around twenty French and foreign speakers (Europe, Israel and the US) and use neural crest cells and the melanocytic lineage, including melanoma, as the main example to understand the links between development and tumorigenesis. Advanced therapeutic applications are also presented. Finally, round tables allow students to think about their future career in science.

Conference themes:
- Development of pigment cells: signaling, differentiation and migration
- Steps leading to tumors and metastasis
- Tumor microenvironment
- High throughput approaches in the analysis of embryos and tumors
- Therapeutic approaches

Round tables:
- Careers in academia and in R and D
- How to write and publish a scientific article ?
- Careers in R and D

Intended learning outcomes ( OAV) :
To acquire an overview of current challenges for basic and translational research in the field of development and cancer.
To discuss and interact with high-level researchers from around the world.
To analyze, interpret and question scientific data linked to the attended conferences, by the oral presentation of a scientific article.

The prerequisites for this course are similar as the ones for the whole curriculum Gene Cell Development: the course is opened to students holding a Master 1 year, with very strong background in cell biology, genetics, epigenetics. Knowledge in developmental and stem cells biology will be useful, but is not required.

Weinberg, The Biology of Cancer Gilbert, Developmental Biology Albert, Biology of the Cell.

Novembre.

ORSAY

Roberto Bruzzone, HKU-Pasteur Research Pole, Hong-Kong SAR, P.R. China Philippe Chavrier, CNRS UMR 144, Institut Curie Chiara Zurzolo, Membrane traffic and pathogenesis unit, Institut Pasteur contact: enseignement@pasteur.fr.

The first module: Vesicular trafficking and signaling (January 13-24) will focus on mechanistic processes that regulate the dynamics of proteins and lipids at the plasma membrane. The practicum will study caveolae dynamics and carbohydrate-based mechanisms to build endocytic pits using chemical biology and imaging techniques.

The second module: Cell shape and morphogenesis (January 27-February 7) will review key biological concepts required to understand mechanical forces and collective migration in development and morphogenesis. The practicum will study the formation of multicellular tubes in vitro, using micropatterns and microfuidics, ans in vivo, using Drosophila and zebrafish embryos.

Applicants may opt to take only one module or the entire course.

This four-week intensive laboratory and lecture course is organized in collaboration with the Institut Curie; it is devoted to the presentation of current concepts and new experimental techniques in the study of cellular functions.

Topics of lectures include functional organization of the cell, polarity and intracellular traffic communication, cellular signaling, cell migration and invasion, stem cells, apoptosis, autophagy, cell-pathogen interactions, cell cycle and mitosis.

The practical course provides training in culture of transfected and infected cells, in vitro reconstitution of cellular functions, gene inactivation and cutting edge techniques of live imaging.

https://www.pasteur.fr/en/molecular-biology-of-the-cell
https://enseignement.curie.fr/en/content/molecular-biology-cell-2016.

Candidates must have a good knowledge of basic laboratory techniques at the Master degree level. The committee of the course will evaluate applications.

Janvier.

PARIS

Contact UPSaclay : Jérôme ARTUS, MCU UPSaclayjerome.artus@universite-paris-saclay.fr Michel COHEN-TANNOUDJI, DR CNRSm-cohen@pasteur.fr Xavier MONTAGUTELLI, Institut Pasteurxavier.montagutelli@pasteur.fr

S. Granon-Cressand, PU UPSaclay, A. Lalouette, Université de Paris, M. Lucas-Hourani, Institut Pasteur, S. Malot, Institut Pasteur, X. Montagutelli, Institut Pasteur, V. Ponticelli, Institut Pasteur, B. Robert, Institut Pasteur, M. Sala, Institut Pasteur, L. Tiret, ENVA, F. Toledo, Sorbonne Université, H. Waxin, Institut Pasteur.

This 5 weeks practical course includes a number of practical sessions, focused on mouse anatomy and pathology, embryology, genetic mapping, behavior, genome manipulation and phenotypic characterization. More specifically, the attendees will: - Map a recessive mutation - Study the genetics of a complex trait - Analyze deep sequencing data - Mine databases for genetic, genomic and phenotypic information - Manipulate and produce pluripotent stem cells cells - Examine the behavior of inbred mice - Characterize phenotypes associated with limb anomalies - Use reporter genes in cultured cells and embryos - Perform in vitro fertilization experiment

These hands-on experiences are completed by a series of lectures dealing with emerging topics and resources in mouse genetics. These lectures are given by national and international experts in the field.

The course takes place in Pasteur Institute (Paris).

This intensive laboratory and lecture course covers the analysis of gene function at all levels: the gene and its product, the cell and its interactions, the embryonic tissues and the whole animal. This course offers a full training program for advanced graduate and PhD students, as well as post graduate biologists and medical doctors willing to work on medical and experimental Mammalian Genetics.
The theoretical and practical parts present methods and techniques used to derive induced pluripotent stem cells (iPS) from differentiated cells, to study behavioral traits, to analyze gene function in embryonic and adult mutants, to map mendelian traits and to identify QTLs. It also illustrates the use of RNA interference to silence gene expression.

OAV :
•To acquire an overview of current challenges for basic and translational research in the field of mouse animal model experimentation and stem cells.
•To design an experimental methodology to answer a given biological question.
•To get organized, to perform several experiments in parallel, over several days by following several protocols.
•To guarantee research experimental protocols and results traceability by writing rigorously a laboratory notebook.
•To design, write and present a fictive scientific project based on the critical analysis of recent scientific articles, and on strategies and technical approaches learned during the course.

The prerequisites for this course are similar to the ones necessary for the Master Gene Cell Development. The course is opened to students with a good knowledge of genetics and basic laboratory techniques of a Master degree level. The course committee evaluate the applications of the candidates (CV, grades, motivation letter).

Many of the practical sessions are similar to the ones described in “Manipulating the Mouse Embryo: A Laboratory Manual, Fourth Edition”. Publisher: Cold Spring Harbor Laboratory Press,US Génétique de la souris : Les organismes modèles. Edition: Belin Sup Biologie Genetics of the Mouse - Edition Springer.

Janvier.

PARIS

Isabelle Guénal, PR UVSQ, Sébastien Szuplewski, MCU UVSQ, Jérôme Artus, MCU PSay, Aurore Rincheval, MCU UVSQ Sylvina Bouleau, MCU UVSQ Vincent Rincheval, IR UVSQ Frédéric Coquelle, MCU UPsay Benoit Maury, IR UVSQ Aude Jobart-Malfait IE INSERM.

This practical course has 2 weeks of full-time manipulations, which allows students to approach different experimental specialties:

- Fly pushing, Drosophila dissection, whole mount immunodetections.

- Cell culture of ESC and iPSC

- Microscopy and FACS and image analyses: optical microscopy (interference contrast or epifluorescence); confocal microscopy; FACS and image analysis on advanced imaging platform (ImageJ, Facs software)

The course takes place partly in a teaching lab, in the flyrooms of the Laboratory of Genetics and Biology of the Cell (LGBC), the imaging platform. The theoretical conferences take place partly at the Faculty of Medicine Simone Veil and partly at Orsay.

Course content:
This practical course provides hands-on experiments to illustrate the properties of stem cells both in vivo and in vitro. Two mini-research projects are conducted that allow students to appreciate the reality of research, its possibilities and its current limitations:

- The first project illustrates on the one hand the self renewing and differentiation properties of mouse Embryonic Stem Cells (ESC) and on the other hand the reprogrammation of fibroblasts into induced Pluripotent Stem Cells (iPSC).

- The second project, based on in vivo genetically lineage tracing, illustrates the role of the intestinal stem cells in the homeostasis of the Drosophila midgut in response to some damages.

Experiments will require advanced imaging and FACS analyses and therefore will involve imaging facilities at the Faculty of Medicine Simone Veil.

Intended learning outcomes ( OAV):
•To acquire an overview of current challenges for basic and translational research in the field of cell biology, development and stem cells.
•To design an experimental methodology to answer a given biological question.
•To get organized to perform several experiments in parallel, over several days by following several protocols.
•To guarantee research experimental protocols and results traceability by writing in a very rigorous way a laboratory notebook.
•To describe, analyze and interpret obtained data in an oral presentation and write them in a publication format.

The prerequisites for this course are similar as the ones for the whole curriculum Gene Cell Development: the course is opened to students holding a Master 1 year, with very strong background in cell biology, genetics, epigenetics. Knowledge in developmental and stem cells biology will be useful, but is not required.

Basic concepts of developmental genetics can be consulted in "Developmental Biology" from Scott F. Gilbert (Eleventh Edition) or in "Principles of Development" by Lewis Wolpert (Oxford University Press). Specific reviews are: -Gastrointestinal stem cells in health and disease: from flies to humans. Li H, Jasper H. Dis Model Mech. 2016 May 1;9(5):487-99. doi: 10.1242/dmm.024232 -.

Septembre - Octobre.

ORSAY - MONTIGNY-LE-BRETONNEUX

Université Paris-Saclay : - François AGNES francois.agnes@universite-paris-saclay.fr - Caroline BORDAY caroline.borday@universite-paris-saclay.fr - Odile BRONCHAIN odile.bronchain@universite-paris-saclay.fr - Sébastien BLOYER sebastien.bloyer@universite-paris-saclay.fr - Frédéric COQUELLE frederic.coquelle@universite-paris-saclay.fr? - Marie-Hélène CUIF marie-helene.cuif@universite-paris-saclay.fr - Morgane LOCKER morgane.locker@universite-paris-saclay.fr - Laurent THEODORE laurent.theodore@universite-paris-saclay.fr - Simon SAULE simon.saule@curie.fr

UVSQ : - Sébastien GAUMER ? sebastien.gaumer@uvsq.fr - Isabelle GUENAL isabelle.guenal@uvsq.fr - Sophie NETTER sophie.netter@uvsq.fr - Anne-Marie PRET anne-marie.pret@i2bc.paris-saclay.fr - Sébastien SZUPLEWSKI sebastien.szuplewski@uvsq.fr.

The student will meet with the internship supervisor to discuss the context and content of the internship project. The student will read the background literature provided by the supervisor on the internship subject and will search the literature independently as well. The student will write a 10- to 12-page report on the relevant background context of the internship subject, the question that will be addressed during the internship and, briefly, the general approach that will be used to address the question. Finally, the student will give a 15-minute oral presentation of the goals, experiments, and expected outcomes of the internship project in front of a jury followed by 10-minute question and answer period with the jury. The student will choose the language, either French or English, of both the written and the oral reports.

Course content: During this course, the students will be tutored in the presentation of a written bibliographic report and oral project presentation. The subjects to be presented will be in direct relation to their internship projects.

Intended learning outcomes:
-to prepare a bibliographic report
-to use conceptual tools and methodology allowing success in this exercise
-to take a constructively critical stance on published work
-to orally defend scientific data and a scientific project
-to synthesize up-to-date knowledge of a scientific fields.

Master 1 level in Genetics, Cell Biology and Developmental Biology.

The reading materials will be specific for each student internship.

Décembre - Janvier.

ORSAY - GIF-SUR-YVETTE

Marie-Hélène Cuif Pr UPSay Jérome Artus MCU UPSay Anne-Marie Pret Pr UVSQ.

A 5.5-6 month long research internship is conducted in various laboratories around Paris Saclay area, Paris area, or in France or abroad. Students report their research after 2.5 months, by an informal scientific discussion. The final evaluation of the work is conducted upon written report examination and oral defense.

A 5.5-6 month long research internship is conducted in various laboratories around Paris Saclay area, Paris area, or in France or abroad. The scientific coherence of the proposed research with the topics of the Gene Cell Development curriculum is evaluated.
Students report their research after 2.5 months, by an informal scientific discussion. The final evaluation of the work is conducted upon written report examination and oral defense.

To have followed the core courses and prepared the bibliograophical research linked to the internship (semester 1).

Not applicable.

Décembre - Janvier - Février - Mars - Avril - Mai - Juin.

Paris Saclay. Paris Area. France. Abroad.