67166 - Pharmacological and Toxicological Biotechnology with lab

Learning outcomes

At the end of this course, the student will gain knowledge in the use of pharmacological methodologies aimed to evaluate biotechnological drugs or innovative drugs. The student will know and will be capable to employ the analytical procedures to evaluate any individual response to the drugs in relationship to genetic variants of the sigle patient. Particularly, the student will be able to: plan in vitro assays to evaluate the pharmacological profile using high-troughput pharmacological assays; to carry out pharmcological assays to evaluate the activiy of biotechnological drugs; to perform a pharmacogenomic profile related to the drug activity.  Furthermore, the student has knowledge on the use of cellular models to analyze biotechnological or innovative drugs. Particularly, the student will be able to carry out : in vitro assays on cell cultures producing recombinant proteins with the aim to evalute the pharmacological effect on target genes and to evaluate the mechanism of action of biotechnological drugs.      

Course contents

Module of Molecular Pharmacology and Pharmacogenetics

Teacher: Prof. Santi Mario Spampinato

Bioanalytical and genomic strategies for drug discovery. Role of biotechnology in drug discovery. Biotechnological approaches to the evaluation of new drugs.

Introduction to molecular approaches for the identification of novel pharmacological targets.

The drug-receptor interaction. Signaling pathways. Experimental procedures and results obtained for the characterization of a new drug target.

Strategies of gene silencing. Penetration and cDNA expression in eukaryotic cells. Non-viral and viral vectors.

Description of the pharmacological assays hightroughput and their correlations with the discovery of innovative biotechnological drugs. Examples of Bret and Fret analysis for the study of interactions between proteins induced by drugs.

Examples of innovative biotechnological drugs and main pos-translational modification: glycosylation of recombinant proteins, the example of darbepoetin.

Glybera the first viral vector marketed as a drug.

Innovative anti-cancer drugs that block signaling pathways.

Pharmacogenetics and Pharmacogenomics: foundations and applications. Examples of pharmacogenetic and pharmacogenomic studies.

Module of Laboratory

Teacher: Dott. Andrea Bedini - To contact the teacher please see the web site of Dr. Andrea Bedini

Gene reporter assay on mu opioid receptor gene in a human neuroblastoma cell line. Evaluation of a neuronal differentiation marker (GAP-43) in a human neuroblastoma cell line exposed to PMA using an immunofluorescence technique.Analysis of a Si RNA in cell lines - Gene reporter assays.

Module of Cellular and Molecular Toxicology

Teacher: Dott. Roberto Tonelli - To contact the teacher please see the web site of Dr. Roberto Tonelli

Discovery and development of a new biotechnological drug: meaning, scope and description of the efficacy and safety profile related to the preclinical and clinical phases. Toxicological studies of biotechnological drugs.

General toxicology: principles of toxicology; definitions and scopes of the toxicology; types of adverse effects; factors conditioning the toxicological effects of biotechnological drugs; adsorbtion, distribution, metabolism and elimination of a toxic compound. Biotransformation of the xenobiotics: activation versus detoxification; toxicogenetics, genetic polymorphisms affecting the metabolism, the transporters, the therapeutic targets.

Mechanisms of toxicity: mechanisms of cellular death (necrosis, apoptosis, autophagy, pyroptosis); genetic toxicity; cancerogenesis.

Systemic toxicology: nature, site and mechanisms of toxicity of biotechnological drugs at the level of the principal organs and systems. Hepatic toxicity; renal toxicity; toxicity on the respiratory system; toxicity on the immune system; toxicity on the central nervous system; toxicity of the skin; toxicity on the reproductive system.

Readings/Bibliography

Material wil be given to all students from the teachers

Teaching methods

Lessons and a laboratory course where each student has assigned a single position

Assessment methods

The exam takes place in two stages: a) delivery of a detailed written report stating in an analytical way the experimental procedures and the results obtained in the laboratory; b) an oral exam structured in two parts. The first part (module of Cellular Pharmacology and Pharmacogenetics) consists of questions on the following topics:new strategies for drug discovery - Therapeutic antisense oligonucleotides - Oligonucleotide pharmacocinetic profiles – Si RNA – DNA eucariotic cellular permeation – Viral and non-viral gene transfer in eucariotic cells – Hightroughput pharmacological assays - Farmaci Biotechnologic drugs used in therapy: Erythropoietin; Darbepoetin; Glybera - BRET assays – Transcription factor analisys - pharmacogenetics: principles and models. The second part (module of Cellular and Molecualr Toxicology) is focused on these arguments: general toxicology: principles of toxicology; definitions and scopes of the toxicology; types of adverse effects; factors conditioning the toxicological effects of biotechnological drugs; adsorbtion, distribution, metabolism and elimination of a toxic compound. Biotransformation of the xenobiotics: activation versus detoxification; toxicogenetics, genetic polymorphisms affecting the metabolism, the transporters, the therapeutic targets. Mechanisms of toxicity: mechanisms of cellular death (necrosis, apoptosis, autophagy); genetic toxicity; cancerogenesis.Systemic toxicology: nature, site and mechanisms of toxicity of biotechnological drugs at the level of the principal organs and systems. Hepatic toxicity; renal toxicity; toxicity on the respiratory system; toxicity on the immune system; toxicity on the central nervous system; toxicity of the skin; toxicity on the reproductive system.The student needs to obtain a positive score (at least 18/30) in both tests.

The written report will be given ten days prior to the conduct of the written examination. Only students with a grade equal to or greater than 18/30 will be able to take the written exam. The vote on the entire course is calculated as the arithmetical mean of thirty, the individual marks obtained in the written report and in the two parts of the written test. Exam registration should be done within one year of the oral exam.

Teaching tools

lessons plus schemes and other figures

Office hours

See the website of Santi Mario Spampinato

See the website of Andrea Bedini

See the website of Roberto Tonelli