Spatial and molecular organization of cells in diseases

A.Y. 2024/2025
6
Max ECTS
42
Overall hours
SSD
BIO/09 BIO/10 BIO/11 FIS/07
Language
English
Learning objectives
The purpose of this course is the training of the participants in the comprehension of how cells are spatially and hierarchically organized and communicate and the way this organization is altered in diseases.
The course is divided into two distinct modules: "High-content imaging and computational aspects of in vitro and animal model systems" is dedicated to the acquisition, processing and comprehension of data obtained from two popular techniques in the world of bioimaging, i.e., functional MRI and optical microscopy, "Analytical challenges and opportunities from multi-omics" to the one of numerical analysis and interpretation of data obtained by means of next generation sequencing (NGS) techniques.
Expected learning outcomes
At the end of the course, the student is expected to acquire the necessary theoretical and practical knowledge for understanding the necessary principles for processing and inspecting tissue and cells imaging results, as well as for the comprehension of imaging data regularly present in literature.
Single course

This course can be attended as a single course.

Course syllabus and organization

Single session

Responsible
Lesson period
Third trimester
Course syllabus
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)
Prerequisites for admission
No prior knowledge is required
Teaching methods
Lectures will be held in presence. Participation is mandatory.
Teaching Resources
Slides of the lectures will be shared, as well as original articles from up-to-date literature.
Assessment methods and Criteria
The exam will be oral.
Applied physics
FIS/07 - APPLIED PHYSICS - University credits: 1
Lessons: 7 hours
Professor: Giavazzi Fabio
Biochemistry
BIO/10 - BIOCHEMISTRY - University credits: 1
Lessons: 7 hours
Molecular biology
BIO/11 - MOLECULAR BIOLOGY - University credits: 3
Lessons: 21 hours
Physiology
BIO/09 - PHYSIOLOGY - University credits: 1
Lessons: 7 hours
Professor: Fornia Luca