2023-2024 / BIOC0736-1

Biomedical strategies

Duration

40h Th, 5h Pr, 35h AUTR

Number of credits

 Master in bio-informatics and modelling (120 ECTS)5 crédits 
 Master in biochemistry and molecular and cell biology (120 ECTS)5 crédits 

Lecturer

François Beaufay, Franck Dequiedt, Emmanuel Di Valentin, Mireille Dumoulin, Moreno Galleni, Frédéric Kerff, André Matagne, Sébastien Rigali, Ingrid Struman, Mohammed Terrak, Marylène Vandevenne

Coordinator

Franck Dequiedt

Language(s) of instruction

French language

Organisation and examination

Teaching in the second semester

Schedule

Schedule online

Units courses prerequisite and corequisite

Prerequisite or corequisite units are presented within each program

Learning unit contents

Applications of Biochemistry and Molecular Biology in the context of human health (diagnosis and innovative treatments of diseases representing major public health problems).

Week #1:

New strategies: towards personalised medicine (2*2h) : I Struman

  • Research of diagnostic and prognostic biomarkers (2 hrs)
Circulating biomarkers: circulating tumor cells (CTCs), tumor DNA, miRNAs, and exosomes

  • New therapeutic approaches: (2h)
Cell and exosome therapy

Nucleic acid therapies (4h): F Dequiedt

  • mRNA vaccines
  • Other mRNA-based therapies
  • RNA interference therapies
  • Antisense applications
  • DNA editing
  • Nanoparticles
Use of viruses (2h) and immunotherapy (2h): C Sadzot

  • Oncolytic viruses (2h):
Principles; Attenuation and/or targeting strategies: example of oncolytic herpesviruses

  • Immunotherapies and CAR-T cells (2 hrs)
Viral vectors (2h): E Divalentin

  • Principles
  • Advantages and disadvantages of the different viral vectors
Bacteriophages (2h Th + 2h TD): M. Terrak

  • Bacteriophages and derived bacteriolytic enzymes (2h Th)
Introduction; mechanism of action of bacteriophages; description of bacteriolytic enzymes

  • Therapeutic applications of bacteriophages and derived enzymes (2h TD)
Discussion of thematic articles on antibiotic resistance and alternative strategies using phage and phage-derived enzymes.

Nanobodies and protein folding (4h Th + 8h TD): M. Dumoulin

  • Degenerative diseases and protein folding defects (4h Th)
Reminder of the structure/function relationship of proteins (globular proteins; intrinsically disordered proteins)

Aggregation of proteins into amyloid fibres: definition and structural characteristics of amyloid fibres. Mechanism of amyloid fibre formation (nucleation/polymerisation, primary and secondary nucleation, role of lipids, role of post-translational modifications, separation and phase transition mediated by intrinsically disordered protein regions). Cytotoxicity of amyloid fibres or soluble aggregates.

Degenerative diseases associated with amyloid fibres: systemic amyloidosis, local and non-neurodegenerative amyloidosis, local and neurodegenerative amyloidosis (Alzheimer's, Parkinson's, spongiform encephalopathies and Huntington's disease): definition, prevalence, associated protein/peptide, symptoms, pathophysiological mechanisms, treatments, etc.

  • Diagnostic and therapeutic applications of nanobodies (TD, 2*2 h)
Definition and unique characteristics of nanobodies (advantages over conventional antibodies)

Diagnostic applications: ELISA, biosensors, lateral flow diagnostic tests, imaging

Therapeutic applications: oncology, infectious diseases, autoimmune diseases

Analysis of documents and articles, video viewing

  • Selection techniques by display (phage-, ribosome-, yeast-display, etc) (TD, 2h) - Application to the selection of Nanobodies.
Technical aspects and advantages/disadvantages of the different display approaches

Examples of therapeutic molecules selected for display

Analysis of articles and documents

  • Approaches enabling proteins to be modified (chemically or enzymatically) to adapt their properties to the needs of the applications (increasing their half-life in the blood, their stability, labelling them with a fluorophore, a radioisotope, etc) (TD, 2h)
Analysis of articles

Illustration of theoretical concepts through analysis of 3D structures and models using PyMOL software (2 hrs): F. Kerff

Students will follow a defined scenario based on several theoretical concepts seen in the course. They will consult public databases and use the main functions of the PyMOL software to analyse selected structures. They will use their own PC and the software will already have been installed during the Structural Biology BO.

Analysis of Protein-Protein and Protein-Ligand interactions, in particular antibodies (3*2h, TD): M. Vandevenne

Use of the BioLayer Interferometry method to measure interactions between antibody fragments and their target antigen. This approach is commonly used in the pharmaceutical and biotechnology industries as a quality control method for batches of antibodies produced. It is used to determine the affinity of an antibody for its antigen on the basis of kinetic measurements monitored in real time.

External speakers: Bacteriophage applications in clinical settings (2 hrs)

Week #2:

The problem of antibiotic resistance (3*4h, Th?): F Beaufay

Genetic and biochemical bases of antibiotic resistance; Detection of resistance genes; Design of new antibacterial drugs; Importance of the human microbiota; Anti-bacterial virulence strategies.

Development of a microfluidic potentiometric test for the detection and identification of bacterial resistance factors against beta-lactam antibiotics (2h, Th): M. Galleni

New bacterial bioactives (4h th +/ 4h, TD): S. Rigali :

  • Strategies for identifying new bioactives (2*2h Th)
  • Analysis tools for bacterial genomes to list and identify bioactive molecules (4h TD).
Analysis of Protein-Protein and Protein-Ligand interaction, in particular antibodies (2*2h, TD): M. Vandevenne

Dicussion articles (2*2h, other): A. Matagne

  • Publication BMP
  • Publication B-lactamase
Illustration of theoretical concepts through the analysis of 3D structures and models with PyMOL software (2h, TD): F. Kerff

Learning outcomes of the learning unit

  • Acquire cutting-edge training in biotechnologies in the healthcare field
  • Train managers capable of working in academic laboratories or biotechnology companies in the health/pharmaceutical sectors (in therapy and diagnostics). The training offered will enable them to grasp the upstream complexity (R&D) of the world of the biotechnology industry.
  • Provide the practical and theoretical foundations underlying the development of new diagnostic tools, innovative therapeutic treatments and the production of molecules for therapeutic purposes.

Prerequisite knowledge and skills

Toolbox prerequisites :

  • nucleic acid techniques
  • protein techniques
  • imaging and experimental models
  • structural biology
In-depth method(s) :

  • Genetic engineering
  • Recombinant nucleic acids
  • Biophysics
  • Protein chemistry
  • Molecular interactions (macromolecule-macromolecule, macromolecule-ligand)

Planned learning activities and teaching methods

The teaching, spread over 2 weeks, will combine theoretical classes, practical and supervised work, directed scientific analyses and participation in seminars.

Mode of delivery (face to face, distance learning, hybrid learning)

Face-to-face course


Additional information:

Classroom-based (theory, practical and practical work) with independent assignments.

Recommended or required readings

Powerpoints and TP/DD notes will be available to students.

Exam(s) in session

Any session

- In-person

written exam ( multiple-choice questionnaire, open-ended questions )


Additional information:

Learning outcomes will be assessed in a multi-modal format, which may include projects, practical exercises, open questions, MCQs, etc.
The assessment will consist of a written examination (60%) with questions on all the lessons. Some questions may incorporate related concepts covered in different lessons within the module.
The TDs and TPs organised during the course weeks will also be assessed and will each be worth 20% of the overall mark.

Work placement(s)

Organisational remarks and main changes to the course

Practical and/or practical work is compulsory. Any absence must be justified and, where appropriate, students are required to put their work in order. If a report is required, it must be completed even in the event of absence. In the event of unjustified absence, the student may not be admitted to the examination.

Contacts

Module coordinator :

Franck Dequiedt

Tel: 04/366.90.28
e-mail : fdequiedt@uliege.be

Co-teachers :

Ingrid Struman: i.struman@uliege.be
Emmanuel Di Valentin: edivalentin@uliege.be
Mohammed Terrak: mterrak@uliege.be
Mireille Dumoulin: mdumoulin@uliege.be
Frédéric Kerff: fkerff@uliege.be
Sébastien Rigali : srigali@uliege.be
Moreno Galleni: mgalleni@uliege.be
Marylène Vandevenne : mvandevenne@uliege.be
André Matagne : amatagne@uliege.be
Catherine Sadzot: csadzot@uliege.be

Association of one or more MOOCs