Ateneo - UPO

After a quick review of gene structure in eukaryotes and prokaryotes, the issue of gene expression regulation will be presented. The first part of the course will deal with prokaryotes gene expression and its regulation. A series of examples will illustrate the possibility of engineering promoters and genes for biotechnological purposes. The second part of the course will deal with the eukaryotes gene expression system and the multiple levels of its regulation. Key issues: 1) chromatin organization and structure, 2) transcription factor structure and function, 3) pre-initiation complex assembly, 4) transcription termination, 5) RNA metabolism and stability, 6) RNA translation. The third part of the course will deal with the mechanisms by which extracellular signals and intracellular cues regulates gene expression in eukaryotes. A particular emphasis will be placed on the alterations of gene expression in cancer and on the regulation of gene expression in function of nutrients availability and the metabolic status of the cell. Basic molecular biochemical and biological techniques will also be presented with simulations.

For the improvement of students background:
- Harper's Illustrated Biochemistry, 29e, Robert K. Murray, David A. Bender, Kathleen M. Botham, Peter J. Kennelly, Victor W. Rodwell, P. Anthony Weil Please note: available on Access Medicine for our students
- Molecular Biology of the Cell - Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter Edition:5th Please note: the 4th edition is available for free on NCBI bookshelf http://www.ncbi.nlm.nih.gov/books/NBK21054/

Suggested textbook:
- Genomes 3 By Terence A. Brown Please note: the 2nd edition is available for free on NCBI bookshelf http://www.ncbi.nlm.nih.gov/books/NBK21128/
- Cell Signalling Biology Professor Sir Michael Berridge http://www.biochemj.org/csb/

- An extended series of reviews evidenced during the course.

Enhance knowledge and operational skills in molecular biology applied to the study of gene expression.
Provide the cognitive tools for the critical reading of literature.
Provide the theorical and operational bases in the molecular biology7 laboratory.

Basic Biology: Prokaryotes and Eukaryotes intracellular organization.
Basic biochemistry: DNA and RNA structure and metabolism, protein synthesis, enzyme proprieties, major metabolic pathways.
Basic molecular biology: concept of gene, gene expression, promoter, transcription factor, RNA synthesis and degradation.

For the students lacking a strong background in life sciences a series of readings will be proposed to improve their skills on those topics.

Slides, videos and webinars will be used extensively throughout the course.Classwork will be complemented by a laboratory introduction and simulations.To enhance students' discussion skills, the following will be used:- Ongoing assessment questionnaires/tests- Literature research activities and individual or group presentations.A copy of the slides and websites used during the course will be available on the DIR website.

Students with physical disabilities, Learning Disabilities or Special Education Needs can request specific services and tools via the Staff Sviluppo e Coordinamento Carriere e Servizi alle Studentesse e agli Studenti, consulting the University webpage: https://www.uniupo.it/en/services/services- students-physical-or-learning-disabilities
Students with disabilities, learning disabilities or special education needs, once they have contacted the University Staff, can refer to the tutor in charge of the course to define the examination modalities, concerning academic aspects.

The exam will be written and will cover the entire course, with 24 multiple-choice questions worth one point each, divided into 11 "Genomic Analysis," 11 "Regulation of Gene Expression," and 2 "Genetics," as well as three open-ended questions, one for each module, worth three points each.

Students with a written exam above 18 will have the option of taking an oral exam on one of the articles presented during the course.

Questions related to the "Regulation of Gene Expression" module will be presented and discussed with students during the course.

Topic 1
Regulation of gene expression in prokaryotes. Review of gene organization in eukaryotes (enhancers, promoters, transcription start sites, introns/exons, transcription termination sites). Control of gene transcription at the levels of: a) transcription initiation rate, 2) splicing and alternative splicing, 3) mRNA stability, 4) RNA-microRNA cross-talk. Organization of transcription factors: structure of DNA-binding and transactivation domains. Main DNA regulatory sequences. Assembly of the RNApol II transcription initiation complex and notes on other polymerases. Methods for studying regulatory elements on DNA, promoter structure, and transcription factor binding sites. Transcription factors and chromatin structure, gene expression, and chromatin remodeling. Post-transcriptional modifications of histones and the histone code. DNA methylation. Other ways to regulate gene expression: alternative promoters, alternative splicing, mRNA stability control, mRNA translation control, miRNA, and RNA interference.
Topic 2
Control of gene expression by extracellular and intracellular signals. How signal transduction pathways regulate gene expression: - the nuclear receptor family - the STAT family - ERK signaling for serum response elements, NF-kB. Methods for studying signal transduction.
Topic 3
Mutations in transcription factors and cancer, nutrition, and gene expression. P53 mutations and tumorigenesis, Hif formation in response to hypoxia, myc amplification and tumors, alterations in the retinoblastoma protein and the cell cycle. Case studies: 1) transcription factors and tumor metabolism, 2) how alterations in metabolism (i.e., dietary habits or cellular energy status) influence gene expression and chromatin state.

Short simulated or in-person laboratory experiences on basic techniques, use of genome browsers to retrieve information on gene expression.

Understanding the mechanisms of gene expression regulation.Ability to answer specific questions and discuss responses.Practical application of this knowledge to understand and critically read the literature.Guided design of experimental approaches that can be used for theoretical or applied research.