Spatial and molecular organization of cells in diseases

1. High-content imaging and computational aspects of in vitro and animal model systems

Human brain diseases through the lens of neuroimaging techniques (7h)
Lesion-Symptom Mapping (LSM). Lectures will be focused on experimental paradigms and computational methods for investigating the anatomo-functional relationship between human brain lesions and related clinical-behavioral outcomes.
Diffusion Weighted Imaging (DWI) and tractography. Lectures will be focused on the diffusion weighted imaging techniques which allow to investigate the structural connectivity (i.e. tractography) of fibers running within the white matter and connecting different cortical and subcortical areas of the brain.
Functional and electro-functional imaging. Lectures will be focused on recording methods for investigating brain activity: functional MRI (fMRI), based on the fluctuations of blood-oxygen-level-dependent (BOLD) signal in the brain which indirectly reflects the underlying neuronal activity, and electrical-imaging approaches, such as Electroencephalography (EEG) with source localization, based on the anatomical localization of specific electrical signals which emerge from the synchronous activity of neuronal ensembles encoding specific stimuli. The joint use of fMRI and EEG will be presented to elucidate the neurobiological concept of "plasticity", i.e the functional reorganization of specific brain function following a lesion, and its application for investigating epileptic patients.

Optical microscopic and bioimage analysis (7h)
Optical microscopy. Basics of optics, brightfield and phase contrast microscopy, fluorescence microscopy, scanning and spinning disk confocal microscopy, super-resolution microscopy (structured illumination, STORM, PALM), multi-photon microscopy, light sheet microscopy. Resolution, detectors, sampling and quantization, digital images.
Digital image processing and analysis. Filters, image restoration and deconvolution, image segmentation and object-based measurements, motion detection (single particle tracking, particle image velocimetry), image analysis tools and communities.

Biophysical characterization and modelling of cells and tissues (7h)
It's a material world: biomechanical characterization of cells and tissues. Basics of mechanics of biomaterials (elasticity, viscoelasticity, plasticity), tools and methods for the biomechanical characterization of cells and tissues (rheology, mechanical tests, atomic force microscopy, active and passive microrheology, traction force microscopy).
It's an emergence: collective cells behaviors. Cell-cell and cell-extracellular matrix interactions, mechanisms of force generation and transmission, emerging properties of cell collectives (polarized collective cell migration, coordinated contractile processes), in vitro models (wound healing assays, adhesion and invasion assays).
Panta rei: phase transitions in tissue morphogenesis, regeneration and disease. Capturing transitions in the physical state of tissues: morphology, structure, dynamics, methods, and mathematical models. Application: the cell jamming / unjamming paradigm in cancer invasion.

2. Analytical challenges and opportunities from multi-omics
Bioinformatics applied to the analytical and numerical treatment of bulk, single cell and spatial transcriptomics data (including hands-on practicals)