博伊特勒书院

The Beutler Institute 2020:  Mammalian Genetics and Applications, detailed program

organised by Véronique Kruys and Cyril Gueydan

Courses(20 sessions)

The learning activity is based on « ex-cathedra »teaching. The objective is to provide the students with a common base of advanced knowledge in the field of Genetics and Molecular Biology and Biotechnology in relation to Immunology and signal transduction.

Examples will preferentially be selected in the field of Immunology and signal transduction.

Courses are intended to stimulate critical discussion on the presented topics.

C1: Introduction to the course of mammalian genetics.

C2: Protein structure, folding, implications in functional analyses.

Primary, secondary, tertiary and quaternary structures of proteins, the protein data bank, Anfinsen paradigm, protein alignments, folding prediction, Levinthal hypothesis, experimental evidence of stepwise folding (cytochrome c), chaperone-mediated folding.

C3: Protein degradation, misfolding and self-aggregation, intrinsically disordered proteins (IDPs). Ubiquitination and proteasome-dependent degradation, degradation of misfolded proteins, PEST sequences, autophagy, protein misfolding, amyloids, polyglutamine diseases, intrinsically disordered proteins: characteristics, prediction, experimental techniques to demonstrate the presence of intrinsically disordered domains, role of IDPs, examples.

C4: Mendelian genetics: introduction to genetics, single gene inheritance, independent assortment of genes, recessive and dominant inheritance, sex-linked gene inheritance, gene linkage, introduction to forward versus reverse genetics.

C5: Sex determination, mechanisms and related disorders.

C6: DNA structure and genome replication. Fundamental aspects and derived applications.

C7: Mutations and DNA damage, DNA damage repair mechanisms. Overview of DNA polymerases, mitochondrial genome, random genomic insertion.

C8: Genetic recombination, homologous recombination, site-specific recombination, transposition and their applications in mammalian genetics.

C9: Genomics: DNA sequencing, genome composition and typing.

C10: CRISPr/cas technology and recent advances.

C11: Basic concepts in gene expression: Transcription.

C12: Translation: eukaryotic machinery and mechanism.

C13, C14: Mammalian transcription machinery. Core promoter, TFIID, Mediator complex, transcription factors, linking signal transduction and gene regulation (NF-KB, STAT, TLRs).

C15, C16: Relations between chromatin structure and gene expression. Chromatin architecture, chromatin modifiers, chromatin remodeling, the epigenome.

C17, C18: mRNA maturation and export. Capping, polyadenylation, splicing, mRNA export
(Alternative splicing allowing IgM/ IgD expression, alternative polyadenylation switching membrane in secreted Igs).

C19: Post-transcriptional control of gene expression mediated by RNA binding proteins, 5’ UTR-mediated control of mRNA translation (IRES, TOP sequences), 3’ UTR-mediated control of translation and mRNA stability, nonsense-mediated decay, stress granules and P-bodies.

C20: Control of gene expression mediated by non-coding RNAs.

Article reading and oral report and discussion: (5 sessions)

Students will have a list of recent articles to read and a group of 2 students will present and critically discuss a chosen article with the other students. 2 articles presented and discussed/session.

Practical work (18h, 12 sessions):

The objective of this practical learning activity is to provide the students with conceptual and methodological skills in relation to gene inactivation by RNA interference in Drosophila S2 cells. The resulting consequences on cell phenotype will be analyzed by molecular biology techniques. Results will be reported in the format of a scientific publication.