Methods: from disease models to therapy

The initial part of the course will provide a general description of methods related to the development of relevant disease models (using diseases studied by SV labs as examples). Various techniques used for disease model characterization will be introduced, with a particular focus on different imaging techniques. Approaches used to develop therapeutically focused applications will also be outlined. The presented techniques will be discussed in terms of their rationale, applicability and limitations. During the second part of the course students will take part in hands-on rotations in participating technological platforms allowing them to put the theory into practice inside a laboratory environment.

The followings topics will be covered during the theoretical and practical parts of the course:

Animal models

- Basis of the legal and ethical framework of research with animals in Switzerland

- Generation and phenotyping of mouse models

- In vivo imaging techniques

Histology

- General introduction into diverse techniques used to prepare samples for bright field microscopy

- Procedures for standard histology stains

- Detection of proteins and mRNA, multiplexing, spatial omics

- Data analysis and interpretation

Light-microscopy

- Introduction into light-microscopy

- Types of microscopes used to assess histological samples in a fast and reliable manner

- Image analysis, strategies to classify tissue samples

Transmission and scanning electron microscopy

- Basic principles of electron microscopy

- Sample preparation

- Sample imaging

- Image interpretation

Biomolecular integrative structural biology

- 3D high-resolution characterization of biological macromolecules

- X-Ray crystallography, single-particle Cryo-EM and Bio-NMR

- Visit and data collection at high-end microscopes at the Dubochet Center for Imaging

- Introduction to 3D protein structure software and modeling tools as well as data interpretation

Academic drug discovery

- Description of the early drug discovery process

- Molecular screening assays (from in vitro target-based to cellular phenotypic high throughput and high content screening)

- Introduction to the basics of chemical libraries, medicinal chemistry and illustration of the hits to leads process

- Advanced cellular models (3D formats and organoids generated from patient samples)

Gene therapy

- Principles of gene delivery to adult tissues

- Introduction to vector technologies and production methods

- Introduction to genetic manipulations in the context of gene therapy (functional restoration, RNA interference, gene editing)

- Examples of therapeutic applications