90817 - Molecular Mechanisms of Diseases

Learning outcomes

At the end of the course, the student knows: i) the genetic and molecular mechanisms of DNA damage and repair, checkpoint activation and genomic instability; ii) functions of disease-relevant protein factors; iii) gene mutations and molecular defects leading to the development of human diseases such as cancer, neurodegeneration, aging and immunological diseases. In addition, the student is able to conduct immunoprecipitation experiments to map protein-DNA interaction sites along the genome.

Course contents

DNA damage and mutations. Base damage and damage to the sugar-phosphate backbone. DNA damage mechanisms: oxidation, alkylation and ionizing radiation. Chemical agents and antitumor drugs.
Mechanisms of damaged base repair. Photlyase, nucleotide excision repair (NER), base excision repair (BER), mismatch repair. Genes and proteins involved in repair mechanisms and hereditary genetic diseases.
DNA cleavage repair: homologous recombination and non-homologous end-joining repair mechanisms. Repair of DNA-protein crosslinks.
DNA damage-activated checkpoint mechanisms. Kinase signalling: ATM/ATR and p53 functions.
Repair gene mutations and neurodegenerative diseases and cancer.
Oncogenes and tumor suppressor genes. Molecular pathways and neoplastic transformation.

The program for the practical laboratory will be the execution of experimental protocols to determine genome instability processes and gene expression, with fluorescence microscopy, real-time PCR, and the interpretation of the data.

Readings/Bibliography

Text book:

1 Capranico G, Martegani E, Musci G, Raugei G, Russo T, Zambrano N, Zappavigna V. Biologia molecolare, EdiSES (last edition).

2 RF Weaver, Molecular Biology, McGraw - Hill (last edition)

Moreover, I will distribute original scientific articles and reviews on the studied topic during the class.

At the start of the laboratory, a written protocol will be distributed for the execution of it.

Teaching methods

The course consists of lectures by the teacher and seminar of the students on specific topics. The teacher will stimulate the students in actively participating in discussions raising questions and expressing personal opinions, in particular during the seminars. Each student will execute the experimental protocol individually and will be stimulated to compare his(her) own experience with other students. At the end of the laboratory, each student has to write a report of the experience.

As concerns the teaching methods of this course unit, all students must attend Module 1, 2 [https://www.unibo.it/en/services-and-opportunities/health-and-assistance/health-and-safety/online-course-on-health-and-safety-in-study-and-internship-areas] online, while Module 3 on health and safety is to be attended in class. Information about Module 3 attendance schedule is available on the website of your degree programme.

Assessment methods

The exam will assess the knowledge of the student on the mechanisms of genome integrity, DNA damage and repair, which are at the basis of human syndromes and chronic diseases such as cancer and neurodegeneration.
The exam will also assess if the student is familiar with experimental  protocols used during the lab practice.
The exam consists of: a) a written report at the end of the laboratory, and b) an oral exam. The oral exam will consist of questions related to the program of the course and a discussion of the written report of the laboratory.
The maximal score is 30/30.

Teaching tools

Power point presentations, PC and internet. The laboratory is fully equipped with instruments and reagents needed for ChIP and real-time PCR.

Links to further information

https://site.unibo.it/capranico-lab/en

Office hours

See the website of Giovanni Capranico