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Regulation of gene expression

Course code:

MS0457

Teacher:

Gianluca BALDANZI

SSD:

BIO/10

Degree program:

Course in Medical Biotechnologies

Year:

I

Semester:

I

Credits

5

Hours

20

Comprehensive course:

Functional Genomics

Academic year:

2014/2015

 

Course objectives

The student will learn 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.

In a second step cancer metabolism will be used as a “case study” to follow how the combined action of master transcription factors integrates with micro-environment promoting an alteration of the metabolic network.

 

Knowledge and skills expectations

  • 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.

 

Course program

Topic 1: Gene expression regulation

Recall of the organization of genes in eukaryotes (enhancers, promoters, transcription start site, introns/exons, transcription termination sites).

Control of gene transcription at the level of transcription initiation rate, splicing and alternative splicing, mRNA stability, RNA interference and microRNA.

Transcription factors organization: structure of DNA binding and trans-activating domains. Major DNA regulatory sequences. Assembly of RNApolII transcription initiation complex.

Methods to study DNA regulatory elements, Promoter structure and transcription factor binding sites.

Transcription factors and chromatin structure, chromatin remodeling and gene expression. Post transcriptional modification of histones and the histone code. DNA mutilation.

Other ways to regulate gene expression: alternative promoters, alternative splicing, control of mRNA stability, control of mRNA translation, miRNA and RNA interference.

 

Topic 2: Control of gene expression by extracellular and intracellular cues.

How signal transduction pathways regulates gene expression:

  • The nuclear receptor family
  • The STAT family
  • ERK signaling to the serum response elements.
  • Myc in growth factors signaling and tumor formation
  • Hif in the response to hypoxia and tumorigenesis
  • P53 mutations, cancer and metabolism


Topic 3: Tumor cell metabolism and the way to study it.

Peculiarities of tumor metabolism, the Warburg effect and beyond.

Methods to study metabolism, integrating gene expression, metabolomics and in vivo data. Use of mass spectrometry, PET/NMR probes, and electrodes (Oxygen Consumption Rate – ExtraCellular Acidification Rate) to study metabolism in living cells/tissues/patients. Experimental manipulation of metabolism and possible routes for cancer therapy.

 

Topic 4: How oncogenes and altered signaling pathways regulates tumor cell metabolism.

Tumor metabolomics, onco-metabolites and the peculiarities of tumor metabolism.

How alterations of signal transduction machinery and gene expression integrates with a peculiar micro-environment to dictate tumor metabolism.

How alterations of the metabolism contributes to tumor development (proliferation, migration, resistance to cell death).

 

Practical training

None 

Optional activities

None

 

Course materials

During the course, slides and webinars will be extensively used.

A copy of the slides and the websites used during the course will be available on the DIR site.

Students will undertake teacher driven research/presentation/teamwork. 

 

Required texbooks / Bibliographic resources

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

 

Methods of evaluation

The final exam for the comprehensive course will consist in a written exam including all the three subjects of the course, namely Genomic Analysis, Regulation of gene expression and Genetics. For each subjects there will be four statements requiring the answer true/false and eventually a brief comment of maximum 10 lines.

The maximum time allowed will be 90 minutes.

The results will be given within three-four days and if the student wishes to increase the grade he/she can do an oral exam.

Notice

Notice for the students of the first year of Master in Medical Biotechnologies

  • Internship notice and form are available for download

  • Three optional basic courses have been activated:
    1. The cell (Prof. FOLLENZI Antonia)
    2. Basic genetics (Prof. GIORDANO Mara)
    3. Background of immunology (Prof. DIANZANI Umberto

    Attendance to these courses is highly suggested.

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