Cellular and Molecular Biology

ADVANCED MOLECULAR BIOLOGY

ADVANCED MOLECULAR BIOLOGY

Academic year 2019/2020

Sommario del corso

• Course objectives
• Results of learning outcomes
• Course delivery
• Learning assessment methods
• Support activities
• Program
• Suggested textbooks and readings
• Teaching tools

Course objectives

This teaching contributes to the learning objectives included into the Fundamental Area of the Master in Cellular and Molecular Biology - Biologia Cellulare e Molecolare, providing knowledge in the post-genomic areas of molecular biology, including genomics, epigenomics, transcriptomics and transcriptional and post-transcriptional regulatory networks; as well as applicative abilities such as i) the analysis of biological databases and genomic browsers; ii) reading and understanding scientific articles in the field that are characterized by quite complex analytical approaches and results representation; iii) research methodology and process deconvolution; iv) complex data analysis.

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 (microarrays, Next Generation Sequencing, epigenomics, protein-DNA, protein-RNA, proteomics), make it possible to represent the organization and control 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 to:

• Updating the basic knowledge of Molecular Biology to the novel discoveries and research approaches opened by the advent of high throughput genome sequencing technologies.
• Reconsidering regulatory Biology, with specific regard on transcriptional and post-transcriptional regulation of gene expression and gene interaction at the network and systems biology level.
• Introductory awareness to the novel, open world of multinational post-genomic projects (ENCODE, FANTOM, 1000 Human Genomes, … …) and biological databases, with tools to download and use data.
• Ability to read and interpret research articles in the field of regulatory genomic molecular biology
• Awareness of applications of the new genomics studies in different fields, with special attention to medicine and neurobiology.

Results of learning outcomes

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

Knowledge:

• the primary analytical methods in Genomics and transcriptomics, comprising the fundamentals of bioinformatics analysis of results
• 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 those networks in human disease

Understanding

• how a molecular biology study, aiming at a knowledge of the above, 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 genomic analysis, in order 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 on a recent scientific article 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

Course delivery

The first part of this course is composed of 5 Chapters, with a total of 36 hours lecturing, plus Moodle's support activities, hands-on bioinformatics laboratory and Students' Report activity, corresponding to 6 cfu. The second part is composed of 24 hours lecturing, reading and discussion of scientific results, corresponding to 3 cfu.

Learning assessment methods

The ability to search, analyse and report results of recent scientific papers on the course subjects is achieved through a practical "Students' report" activity. It is evaluated as such, together with an evaluation of Student's participation to e-learning support activities.  1) congruence; 2) difficulty; 3) contextual framework; 4) analysis of results; 5) comprehension; 6) clarity of report, are graded. The level of participation in support activities and bioinformatics hands-on laboratory is evaluated as % participation, quiz or lesson execution, and writing in methodological Wikis. Grading is out of 30, with "cum laude" counted as 33/30.

The ability to interpret experimental results and schemes is evaluated by a Moodle-based test, which is composed of 15 questions in which, based on Figures extracted from scientific papers or reviews discussed during course lectures, Students are required to answer questions (multiple choice, short answer, short essay). Grading is out of 30, with "cum laude" counted as 33/30.

The ability to expose and discuss course topics is evaluated through a short interview, usually no longer than 30 minutes. During first 10 min Students are expected to expose a general topic at Teacher's choice among a list published in advance on the course website. There will be no break and no question in this first period. A specific question may be offered at the end. Finally, during last 10 minutes, a Figure from one of the 4 Research Papers discussed during the course is chosen and Students are required to explain in detail the experiment.  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.

Due to the current modality of exams "in remote". as agreed with the Students, this last 10-min question will be proposed as a 15-min Moodle test with three random questions of the "Cloze" type, each containing text, figures and 4 embedded multiple choice or short answer questions. This change will concern all student of the 2019 cohort.

Support activities

Support activities are organized on the Moodle e-learning platform (http://cmb.i-learn.unito.it/ ). Activities such as quizzes, lessons, and guided website visualization are posted and participation monitored. Two students' wikis are organized, one for the search of Research papers for Students' Report and one concerning methodological aspects. Last, for each chapter of the course, Research papers are posted that Students must read and that are discussed thoroughly during the lessons.

Program

Genomics and post-genomics. NGS technologies. Chromatin components and functional states, epigenomics. International projects addressing genetic variation and functional genomics. Biological databases and genomic browsers.

Nuclear topographic organization, chromosomal territories, eu- and hetero-chromatin domains and methodology to study the 3D genome. Genomic imprinting, chromatin dynamics during development.

Transcriptomics, microarray and RNA-seq technologies. Transcriptional units and transcript variants. Non-coding RNAs. RNA biogenesis and processing mechanisms and methodology.

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.

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.

The role of transcriptional enhancers and Super-enhancers in cell identity definition, in tumor progression and in other diseases.

Genomics and epigenomics of model neurological diseases.

There is no specific textbook for this course. For basic and general reference, recent (>2010) editions of any Molecular Biology textbook for undergraduate students will be OK.

As a support for the study of this course, specific scientific Reviews are posted on the Moodle course website. Websites containing support videos, texts, images and other materials are also indicated.

Class schedule

• Teaching materials
• Exams and finals
• Go to Moodle
• Visit the forums