The Membrane Receptors and Cell Signaling Group
Our attention is focused on the molecular mechanisms of receptor signaling. Understanding the mechanisms involved in the transmission of information from the external environment to cells is extremely important from a medical point of view, since many pathological conditions are directly or indirectly related to the dysfunction of signaling systems. Recent advances and successes in many areas of modern pharmacology depend precisely on knowledge of these mechanisms and the ability to intervene in a suitable manner to regulate cell signaling.
By using methods of molecular pharmacology and biochemistry, we study select trans-membrane signaling systems, focusing on receptors coupled with trimeric G proteins (GPCRs), specific G proteins and effector molecules (such as adenylate cyclase and phospholipase). The properties of these systems and their components are examined in vitro on model cell lines as well as in tissue or organ samples, enabling results to be obtained corresponding to natural physiological conditions. The primary aim of these studies is to discover new knowledge about the organization and function of cell signaling systems, although the potential use of this information for medical purposes is also important.
At the present time our research is particularly focused on the following areas:
- Study of the general principles associated with the process of information transmission and desensitization of hormone response, analysis of receptor signal complexes and examination of the role of membrane rafts during the transmission of signals through select GPCRs. We are primarily interested in adrenergic, adenosine, opioid and cannabinoid receptors and the properties of their signaling systems in various physiological contexts.
- Characterization of GPCRs and their controlled signaling systems in cardiac muscle and brain tissue during adaptation to chronic hypoxia or cold.
- Monitoring of potential cytoprotective effects of opioids or cannabinoids and the effect of these substances on signaling controlled by G proteins in the brain and heart.
- Examination of the role of oxidative stress and cell death during various adaptive processes (hypoxia, cold, long-term effect of certain drugs via GPCRs).
- Study of the significance of communication between opioids and TRPV receptors in the modulation of nociceptive signaling
In the laboratory a broad spectrum of methods is used, ranging from work with cell cultures and animal models to molecular biology techniques, receptor binding studies, measurement of enzyme activity and determination of the functional status of select signaling systems, as well as separation techniques and advanced protein analysis including proteomic approaches.
Doc. RNDr. Jiří Novotný, DSc.