Advanced molecular biology

A.Y. 2021/2022
9
Max ECTS
80
Overall hours
SSD
BIO/11 BIO/18
Language
English
Learning objectives
The last 10 years have seen a revolution in the possibility to study the regulation of DNA metabolism at the single cell and single molecule level in live cells. Sophisticated technologies allow us to quantify movements, interactions and dynamics of the actors impacting on genome biology. The course of Advanced Molecular Biology aims at providing a deep overview of the mechanisms that regulate cellular processes in complex organisms in health and disease. In particular, mechanisms controlling cell division, proliferation and quiescence are integrated with processes required to maintain the integrity of the genome; on the other hand, cell plasticity and adaptation are required for cellular homeostasis and response to environment. The input comes from the genome; genome structure and function maintain cell identity and regulate transcription through a plethora of different and integrated epigenetic mechanisms. Genome integrity, transcription, tridimensional organization and compartmentalization in the nuclear space are quantitative and dynamic parameters that, occurring at single cell level, govern tissue organization and specialization. These topics will be discussed in model organism and in mammalian cells, with a particular focus on human pathologies, especially cancer, linked to alterations in the molecular mechanisms of these processes. Students will also become familiar with advanced approaches in molecular biology and cutting edge biophysical methodologies to obtain quantitative data on proteins-proteins, protein-DNA interactions, reversible post-translational modifications, nucleic acid processing.
Expected learning outcomes
After this course, the student will be:
-familiar with the mechanisms underlying cell proliferation, differentiation and its regulatory circuits
-experts in key transcriptional networks that control cell growth, proliferation, DNA repair and their alteration in cancer
-familiar with the molecular mechanisms responsible for preserving genome integrity and their role in counteracting tumorigenesis
-familiar with the epigenetic layers that define a specific epigenome and their possible alteration in diseases
-experts in the methodologies and cutting-edge technologies to study single molecules and their interactions, and to interpret protein networks involved in cancer
-able to critically evaluate the advantages and disadvantages of model systems to study molecular processes
- design the best experimental strategies to answer a specific scientific question;
- critically evaluate hypotheses and working models
Course syllabus and organization

Single session

Responsible
Lesson period
Second semester
More specific information on the delivery modes of training activities for academic year 2021/22 will be provided over the coming months, based on the evolution of the public health situation.
Course syllabus
- The genome organization in eukaryotic cells
- Non-coding RNAs
- DNA repetitive elements and genome responses
- Epigenetic regulation of gene expression (DNA methylation, histone variants and modifications, chromatin accessibility and ncRNAs association, etc), technologies and alterations in human diseases
- Tridimensional organization of the genome (polymer folding principles, TADs and long-range interactions), technologies and alterations in human diseases
- Genome regulation through compartmentalization and liquid liquid phase separation (nucleolus, transcription factories and repression bodies, LADs, nuclear pore, RNAs etc), technologies and alterations in human diseases
- Molecular tools for genome editing (CRISPR/Cas9)
- NGS sequencing approaches for an omics view
- Single cell RNA sequencing and cellar heterogenicity
- Single molecule tracking to study transcription factors dynamics in the nucleus
- Super-resolution imaging approaches to study the localization of transcription factors and accessible regions of the genome.
- Molecular genetics approaches to study protein/DNA, protein/protein and protein/RNA interactions at the single molecule resolution.
-Quantitative analysis of morphogen gradients during development, in Drosophila
- In vivo imaging to study key DNA metabolic factors mediating cancer cell proliferation and metastasis
- 3D cultures, organoids and tissue modeling in health and disease
- Cellular and molecular response to environment (mechanotransduction, oxidative stress, heat shock genes response, molecular control of cyrcadian rithms, tumor microenvironment, etc).
Prerequisites for admission
The course will require basic knowledge of cell biology and biochemistry and a good knowledge of molecular biology and genetics. Students must be aware of the principles of the DNA metabolisms, notably transcription, replication, repair and recombination. They must have knowledege of concepts related to cell growth, cell cycle progression, cell differentiation, and basic knowledged of formation of organs and tissues. They must be aware of concepts related to multi-subunit protein complexes, and on the principles of enzymatic activities.
Teaching methods
Traditional lectures supported by slides integrated by on-site interactive discussion sessions, in which student's involvement will be promoted through assignment of scientific papers in advance, with the purpose of stimulating group discussions and to develop students' critical and communication skills.
All the teaching materials will be available through the Ariel or Teams platform.
Regular attendance is strongly suggested.
Teaching Resources
The topics covering most of the course are novel and as a consequence there is no comprehensive text. Web sites and review papers will be indicated to the students. Lectures or recorded lessons will be made available through the Teams and/or Ariel platforms, together all the materials instrumental to allow the students to participate to the on-site discussion lessons, such as original articles and reviews.
Assessment methods and Criteria
Learning assessment will be through an oral exam at the end of the course. Examples of exams will be presented during the course.
BIO/11 - MOLECULAR BIOLOGY - University credits: 0
BIO/18 - GENETICS - University credits: 0
Practicals: 16 hours
Lessons: 64 hours