RTG 2515: Chemical Biology of Ion Channels (Chembion)

Basic data for this project

Description

Ion channels control electrical and chemical signalling in all cells of the human body and thus, a plethora of physiological processes. Therefore, dysfunction of ion channels often leads to pathological processes and diseases (channelopathies). “Chembion” is devoted to harness chemical methods and develop powerful pharmacological tool compounds to gain insight into the function and (patho)physiology of ion channels. In the second funding period, we will intensify the theoretical structural analyses of ion channels and their interactions with ligands to fuel the rational development of subtype-specific ligands and tool compounds (e.g. imaging probes). The action of the developed agonists, antagonists, and tool compounds will be investigated at the molecular and cellular level. The overarching aims are to elucidate the integrative channel (patho)physiology and provide new powerful tools therefor. Five families of ion channels were selected as model systems to address these key objectives: NMDA receptors, CatSper, HCN, KCa3.1 and Kv7 channels. The molecular structures of these ion channels are known, including that of the exquisitely complex CatSper channel. Thirteen PIs with complementary expertise will work together to improve the understanding of these ion channels. The Slo3 (KCa5.1), Kv7, and CatSper channels possess a steroid-binding site. In the second funding period, a new focus will be laid on the development of steroid-based subtype-selective Slo3, Kv7.1, and CatSper agonists, antagonists and tool compounds (e.g. photo-affinity probes). Stimulated by the very successful interdisciplinary collaborations well-established within Chembion, we aim at further overcoming the barriers between the molecular world in the faculty of chemistry and pharmacy and the world of cellular and functional system in the medical faculty. Therefore, all projects are joint undertakings with supervisors from both faculties. The RTG Chembion has established a well-structured, research-oriented and interdisciplinary training in an excellent scientific environment. Key features of the qualification program are: (1) early international orientation already during the doctoral studies. All doctoral researchers of the first cohort performed parts of their scientific work in a laboratory abroad. (2) Fostering independent and self-responsible behavior by promoting the independent selection of labs for lab-rotation and organization of small international symposia. (3) Promotion the academic and scientific independence and essential “transferable skills“. Within the framework of the Medizinerkolleg MedK, highly motivated and excellent medical students are integrated as doctoral researchers in medicine (Dr. med.) in our RTG. The interaction of doctoral researchers of the natural sciences faculty and the medical faculty is incredibly stimulating for both sides and has to be maintained.