UCL - Pharmacogenomics and toxicology

[FARM2139]

[45h] 5 credits

This course is taught in the 1st semester.

Teacher(s): Pedro Buc Calderon(coord.), Vincent Haufroid, Miikka Vikkula

Language: French

Level: Second

Aims
Main themes

Aims

A. To allow the students the understanding of the main mechanisms of toxicity as well as to give them a basic knowledge for the management of a toxicological dossier.

B. Part B of this course aims to deepen the student's knowledge on molecular genetics, and especially in the field of pharmacogenomics. The objective is to understand the variability in the human genome, its various polymorphisms, and their frequencies and evolution, as well as importance of genetic variations for pharmacological treatment. Influence of these polymorphisms on response to treatment will also be discussed.

Main themes

A. To discuss the basic concepts of regulatory toxicology. The risk assessment procedure is discussed by using both in vitro and in vivo methods. The mechanisms of toxicity are discussed by starting from the formation of reactive intermediates (free radicals and electrophiles), followed by their interaction with biomolecules (lipid peroxidation, protein and nucleic acid adducts, mutation and cancer), loss of cell homeostasis (hypoxia, oxidative stress, etc), the activity of cell defence systems (superoxide dismutase, catalase, vitamin E, etc), and finally cell death (necrosis and apoptosis).

B.
1. Definitions of various polymorphisms (SNP, STRP, CNP).
2. Other reasons for interindividual variability (expression: promoters, methylation, acetylation, LCRs,).
3. Differences between germline, post-zygotic and somatic variability.
4. Techniques to detect genetic variations and expression differences.
5. Importance of variability for development, disorders and therapeutic response.
6. Evolution / future : personalized medicine.