Bioinformatic aspects of nuclear receptors in pharmacotherapy

IN ENGLISH LANGUAGE Candidate: Mgr. Josef Škoda Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of the doctoral thesis: Bioinformatical aspects of nuclear receptors in pharmacotherapy The liver plays a central role in energy homeostasis via processing post-prandial excess energy into storage molecules and reusing stored energy via gluconeogenesis during the fasting period. This tight energy balance is maintained by a myriad of regulating processes. Dysfunction of metabolic control is a key event of severe diseases in today's population, starting with obesity, insulin resistance, and metabolic syndrome, proceeding to end-stage complications in type 2 diabetes, whole organ malfunctions, or even tumor diseases. Master players in metabolic regulation are nuclear receptors (NR) activated by endogenous stimuli or scavenging for nutritional or toxicological signals. NRs regulate gene transcription activation and therefore maintain liver metabolic plasticity. In this thesis, modern molecular biology approaches were used to study ligands of NRs and the effects of their treatment. After the typical activation of a NR, hundreds of genes are regulated, which is beyond the ability to study with conventional biology methods. For this purpose, omics methods are an ideal solution. They are characterized by..