Cellular and Molecular Biology

ADVANCED MOLECULAR BIOLOGY (Biomedical)

ADVANCED MOLECULAR BIOLOGY

Academic year 2023/2024

Sommario del corso

• Course objectives
• Results of learning outcomes
• Program
• Course delivery
• Learning assessment methods
• Support activities
• Suggested readings and bibliography
• Notes
• Class schedule
• Teaching tools
• Course card

Course objectives

This teaching contributes to the learning objectives included in the Fundamental Area of the Master in Cellular and Molecular Biology (Biologia Cellulare e Molecolare). The first objective is knowledge in the areas of genomics, epigenomics, transcriptomics and transcriptional and post-transcriptional regulatory networks. The second objective is to acquire the following applicative abilities: 

• recovering essential information from genomic browsers and  biological databases; 
• understanding scientific articles in the field, through the ability to deconvolute the approach and methodology and derive information from representations of omics and complex data.

Students will acquire an advanced level of knowledge on the activity of genes and genomes and the mechanisms of genome regulation at the transcriptional and post-transcriptional level, in the contexts of development, differentiation, cellular homeostasis and cancer.

In the first part of the course, Students will understand how the modern global methods (Next Generation Sequencing, epigenomics, protein-DNA, protein-RNA, proteomics), make it possible to study the organization and regulation of most evolved genomes.

In the second part of the course, Students will acquire the ability to use their theoretical knowledge in solving applicative problems, with special regard to biomedical issues, through the analysis of relevant literature.

Specific objectives are:

• Updating basic Molecular Biology in the light of research approaches opened by the advent of high throughput genome sequencing technologies.
• Reconsidering regulatory Biology, with specific regard to epigenomics, genomic programming and reprogramming, in addition to transcriptional and post-transcriptional regulation of gene expression. 
• Introductory awareness of gene interaction at the network and systems biology level.
• Ability to read and interpret research articles in the field of regulatory genomic molecular biology
• Applications of “omics” studies in different fields, with special attention to medicine and neurobiology.

Results of learning outcomes

Expected outcomes, divided into "knowledge, understanding, abilities", are:

Knowledge:

• the primary analytical methods in genomics, epigenomics and transcriptomics
• the most important modalities of transcriptional regulation in higher Eukaryotes.
• the mechanisms of alternative RNA transcript generation, including non-coding RNAs and associated functions.
• the mechanisms of global post-transcriptional gene expression regulation
• the constitutive principles of gene regulatory networks
• the involvement and the changes of components of these networks in human disease

Understanding

• how a molecular biology study is planned and conducted; how results are presented and discussed in a primary scientific journal; and finally how results must be understood and analyzed in the framework of current knowledge.
• the methodological approach (among those studied) that should be used to answer a specific scientific question.
• The kind of information that can be obtained from -omics studies, to understand the molecular mechanisms associated with diseases and how this knowledge can be used to develop a potential therapeutic strategy

Abilities

• To carry out relevant literature searches on the course topics
• to search for information on, and expose a summary of, the main methods of genomics and functional genomics
• to analyze, interpret and report publicly recent scientific studies concerning one of the course topics, including the methodology used
• to interpret results and diagrams relating to the main issues discussed
• to expose concisely the topics of the course, as organized in basics, novelties and methodology.
• to individuate which methods should be used to address a specific problem in the field

Program

1. Genomics: sequencing genomes by NGS technologies. Features of genomes in higher Eukaryotes. Genomic variation and variant classification. Mutation and repair, rates of spontaneous mutations. Repetitive and Transposable Elements. Sequence databases and genomic browsers.
2. Transcriptomics: the transcribed part of genomes. RNA-seq technologies. Classification of transcripts and mature RNAs. Coding and noncoding genes and transcripts. RNA isoforms and classification. Noncoding RNA classification and functions.
3. Epigenomics. Chromatin components and functional states, Nuclear topological organization, chromosomal territories, eu- and hetero-chromatin domains. Methodology to study the 3D genome. Genomic imprinting, monoallelic expression and chromatin dynamics during development.
4. Regulation of gene transcription. Promoter types, CpG methylation, nucleosome positioning and PTMs. Mediators and Coregulators.Transcriptional activation. Enhancer programming. Pioneer, tissue-specific and signal-dependent Transcription Factors. LncRNA role in transcriptional regulation and chromatin dynamics.
5. Post-transcriptional regulation: alternative splicing, regulatory factors and mechanisms. Stability, decay and intracellular localization of RNAs. RNA interference. MicroRNA, lncRNAs and transcriptional/post-transcriptional regulatory circuits.
6. Epigenetics in disease: Alterations of DNA Methylation, histone acetylation and deacetylation, chromatin remodelling factors
7. CRISPR technology: description of several CRISPR systems, therapy for Fragile-X-syndrome and Progeria.

Course delivery

Module A is composed of 4 Chapters, with a total of 42 hours of lecturing, accompanied by Moodle's support activities with tutoring (see below) corresponding to 5 CFU. 

Module B is composed of 24 hours of lecturing, reading and discussion of scientific results, corresponding to 3 CFU. The practical lab on CRISPR technology applied to scientific problem is composed of theoretical part and practical activity in the laboratory corresponding to 1 CFU.

All lectures will be delivered in presence, subject to updates on the measures adopted by UniTo which can be found on the University portal under "Provisions for those who study and work at UniTo" (see https://en.unito.it/studying-unito)

Learning assessment methods

1) The ability to search, understand and report results of recent scientific papers concerning any of the course subjects will be evaluated. Grading will consider: 1) congruence; 2) difficulty; 3) contextualization; 4) analysis of results; 5) comprehension; and 6) clarity of report. 

Grading is out of 30, with "cum laude" counted as 33/30. Normally, Student reports will be done at the end of Module A, and the grade is kept for the final exams. For students presenting their report at this time, an additional bonus of up to 3 points will be granted, proportional to the Student’s participation in Moodle support activities (see below). For Students not reporting during the course, the exam will also contain this assessment: Students will be given a recently published paper, allowed 2-3 hours for reading and then required to expose its main features orally with questions. 

2) The ability to interpret experimental results will be evaluated by a Moodle-based test, composed of 20 questions.  Students will be required to answer multiple-choice, short-answer, or short essay questions concerning Figures extracted from scientific papers or reviews discussed during course lectures. Grading will be out of 30, with "cum laude" counted as 33/30.

3) Knowledge will be evaluated considering the ability to expose and discuss course topics during a short oral interview. In the first 10 minutes, Students are expected to expose a general topic randomly extracted from a list of topics published in advance on the course website. Specific questions may be offered at the end. During the last 10 minutes, Students will be required to explain in detail one experiment from one of the 4 Research Papers studied during Module A. Grading is out of 30, with "cum laude" counted as 33/30.

The final grade is the arithmetic mean of the three single grades. The "cum laude" is assigned when one of the single grades is "cum laude" (33/30) and the general average is above 30. 

EXAM modality. 

The tests will be performed in any case on the Moodle “Piattaforma Esami”. Time: 1 hour. Before performing the test, Students are required to read the Ethical Code: https://www.unito.it/sites/default/files/allegati/01-08-2014/cod_etico_comunita_universitaria.pdf

An English translation is provided here: Code of Ethical Conduct

Support activities

Support activities that will be timely proposed on Moodle e-learning platform (quizzes, databases, wikis) and are designed to help and consolidate comprehension of the lecture subjects and will be done by Students either by themselves during a fixed period of time, or by taking advantage of the Tutoring sessions that accompany each lecture set. Participation in the Activities will be monitored.

Tutoring will be granted in person and online and will concern the subjects of the lectures. There will be 3-hours of tutoring accompanying the three lectures per week. 

Last, for each chapter of Module A, one Research Paper is posted in Moodle. Research Papers are discussed thoroughly during the lessons and will be the subject of one question during the exam oral interview. 

Auxiliary materials are on the Moodle site: https://cmb.i-learn.unito.it/course/view.php?id=508

For Chapter 1, I refer to ch. 4-5 from T.A. Brown, Genomes 5, Garland Science, 2023.  We will provide slides, transcription and other reference materials including websites.

For Chapter 2 on chromatin and epigenetics, you can refer to the free e-book  “Introduction to Epigenetics”, Springer 2021, by Paro, Grossniklaus, Santoro and Wutz at: https://link.springer.com/book/10.1007/978-3-030-68670-3. Chapters 1-3 (in part 4)

For Chapters 3 and 4, as well as for Module B refer to the slides and to the Review Articles that are available on the Moodle site:
https://cmb.i-learn.unito.it/course/view.php?id=508

Notes

Studying proficiently Advanced Molecular Biology, which is one of the fundamental courses in this Master, requires constant and continuous participation, exercise and study.

The knowledge Students acquire in Lesson N will be essential to understanding Lesson N+1, whose content will be essential for understanding Lesson N+2, and so forth.

Class schedule

• Teaching material
• Exams and finals
• Class schedule
• Go to Moodle
• Register for the course
• Enrolled students
• Invia email agli studenti registrati
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