Parcours Structural biology of pathogens 2e année

The course starts with an introductory lecture that describes how scientific projects are usually performed. Major points discussed are:

1) Structure and functioning of a scientific team („From Einstein to Frankenstein – what makes a modern scientist“)

2) Scientific literature (critical reading of publications, building blocks of a publication, the „hidden“ information)

3) The „value“ of a publication (impact factor and its consequences; ethics in publishing)

4) Project planning and funding proposals (including funding agencies and fellowships)

5) Financial and structural resources for a scientific project

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The course will present practical and theoretical aspects of the classical approaches used to determine the structure of macromolecules by X-ray crystallography and Nuclear Magnetic Resonance spectroscopy. The program of this course is described below:

  Part I - Crystallography - 20h

• Crystallization techniques                                                                            
• Crystal symmetry and space groups                                                                      
• Diffraction                                                                                                    
• Structure factors, reciprocal space etc                                                      
• Tutorial: Data treatment                                                                                          
• Phasing – MIR, SAD, MAD                                                                        
• Molecular replacement, crystallographic symmetry                                              
• Tutorial: MAD Phasing                                                                                              
• Tutorial: Molecular replacement                                                                             
• Refinement                                                                                                  
• Tutorial: Model building and refinement                                                                  
• Practical lab: Crystallization on a PSB platform                                                                 
• Practical lab: X-ray data collection on a ESRF beamline                                                  

    Part II – Nuclear Magnetic Resonance-20h

• NMR principles: active nuclei, magnetic field, radiofrequency excitation,
             return to equilibrium                                                                                     
• NMR observables in the spectra of biomolecules (chem. shift, scalar
             couplings,  linewidth)                                                                        
• NMR observables: measurement                                                               
• Practical lab on IBS-NMR platform: data collection
• The steps to structure determination: sample preparation, isotopic labeling
• The steps to structure determination: assignment   
• The steps to structure determination: extraction of structural parameters 
• Tutorial: Data analysis                                                                                 
• Structure calculation: principles                                                                              
• Practical lab: Protein structure calculation                                                  

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The course aims at introducing the students to advance and modern methods in structural biology that integrate structural and/or dynamical information at different levels of resolution.  

- Structure of large biomolecular assemblies

•  Obtaining key information on large biomolecular assemblies and systems
•  Electron microscopy and tomography
•  NMR spectroscopy
• X-ray and neutron diffraction
• Hybrid approaches (combination of high- and low-resolution structural methods)
•  Structure of ribosome, signal recognition particle, viruses,…

- From macromolecules to the cell

•  High resolution optical microscopy
•  Atomic force microscopy
•  Correlative electron microscopy (combination of optical and electron microscopy)
•  Structure and dynamics of the cytoskeleton
•  Biology of flower …..

- Dynamics of biomolecular systems

•  Dynamics by NMR spectroscopy
•  Neutron spectroscopy
•  Molecular dynamic simulations
• Intrinsically disordered proteins

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The course will present new developments in the structural characterization of macromolecules and their applications in biology, as well as new major discoveries in structural biology. For each topic, the course will include a lecture by a specialist in the field that will provide an overview of the subject, of the current state of development and of the future prospects. The course will address topics such as time-resolved crystallography, solid-state NMR, molecular dynamics simulations, single molecule observation and manipulation, as well as recent examples of applications taken from the literature. Each topic will also include presentations of recent publications by the students.

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Course outline

The lectures present the basic methodology and some advanced techniques used for high throughput in vitro small molecule drug discovery. The principles and statistical methods used for assay optimization and validation will also be explained.

I. Molecular biology, Biochemistry and Protein expression

II. Proteomic analysis; Mass spectrometry

III. Lab-chips and Cell-chips

IV. Structural biology: Crystallogenesis and Crystallization; RMN

V. Combinatory chemistry

Format of exams:  Oral exam (at the end of December) and Research project (at the beginning of January)

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Course outline

 At the end of the course, the students should be able to analyze a "omic" dataset. More precisely, they should be able.

1- to load, explore and summarize graphically a dataset.

2- to compute confidence interval estimates for proportions, means and variances.

3- to formulate hypotheses, compute tests statistics, interpret p-values and make practical decisions for the standard parametric and non-parametric tests.

4- to adjust simple and multiple linear models, analyses of variance (anovas), logistic regression, Cox model.

5- to select genes that explain a response variable by applying multiple testing approaches.

6- to analyze a data set of differential gene expression.

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Presentation and analyses of scientific publications on the following topics (with the help of experts in the relevant fields):

• Bacterial transcription
• Clinical and experimental evolution of bacterial pathogens
• Cell division and export systems in Gram-positive bacteria
• Cell biology and gene regulation of host/bacterial pathogen interactions
• Biochemistry and regulation of oxidative stress in bacteria.

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Introduction

Science, academic research and entrepreneurship

Innovation

Intellectual properties & juridical forms of companies (in French language due to the specific aspects of the French law)

Marketing of innovation

Customer segmentation

Business development

Project management

Market research

Business plan

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The student will spend 6 months in a research team to work on a scientific project dealing with at least one of the fields covered by the Master 2 ISB program.

Finding the research team and the subject relies on the student.

A proposal for this internship should be sent to the module’s coordinator during the spring/early summer of the previous academic year for validation: It must fit to at least one of the fields covered by the Master 2 ISB program.

The student will be supervised in the lab by a researcher of the field.

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In order to obtain a Master’s degree at UJF, students must demonstrate the capacity to perform at an “independent” (B2 of the CEFRL) level in a foreign language. A foreign language certificate at this level or a non-francophone status meets this requirement. At UJF, the English language skills evaluated for this obligation are:

1)    Reading comprehension of scientific texts

2)    Oral presentation of scientific content related to the student’s field of study

3)    Note-taking from oral sources related to the student’s field of study

This course allows students to show proficiency at the “independent” B2-level in oral presentations and note taking linked to their fields of study.

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Choix d'un ETC si niveau anglais >= B2

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