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Autobiography of Georg Nagel

Georg Nagel

Georg Nagel

Born in Weingarten, southern Germany, as the first of five children, I became seriously ill at the age of five. When my brother and sisters went skiing in nearby Austria, I built a steam engine or a radio from the science education kit which my parents gave me for Christmas every year. My summer school vacations were often spent undergoing surgery at the University hospital of Wuerzburg, a pretty city in northern Bavaria. In school I loved math, physics, and biology and decided on studying biology at the newly founded University of Konstanz, near the Swiss mountains and a beautiful big lake.

 

I liked the strong focus on biochemistry and the structured curriculum of the biology course. Ernst Bamberg, my first lecturer in biophysics, gave me the chance to assist with exciting experiments in his lab for which I even got paid. He measured the opening and closing of a single ion channel (gramicidin) in an artificial membrane. After the diploma — with a thesis on dimerized gramicidin in a lipid monolayer — I did not feel ready to continue for a PhD. Instead, I worked as a teacher at a Swiss private high school and started, with others, “Café Chaos” in downtown Konstanz. Then I again had surgery in Wuerzburg and finally the inflammation in my bones could be stopped. I continued for some time as a teacher, even started hang-gliding in my free time, but when Ernst Bamberg invited me to move with him to Frankfurt, I readily took this chance. 

 

Bamberg led a new research group at the Max Planck Institute (MPI) of Biophysics. At the MPI, I felt fortunate to learn and practice the “patch clamp technique”. There I met for the first time Peter Hegemann who, as a PhD student from MPI Munich, did many of his experiments in Bamberg’s lab in Frankfurt. For my thesis I also applied another new technique, the electrophysiological characterization of the sodium pump (Na/K-ATPase) by the UV light-induced concentration jump of ATP from “caged ATP”. After my PhD studies I spent two years as a postdoc with Clifford Slayman, Yale University, USA. This was a great place to “grow up” in science and to meet many eminent scientists. At Yale, Biff Forbush, the first to use caged ATP for elegant experiments on the sodium pump, impressed and helped me a lot. 


In 1990 I continued at Rockefeller University, NY, in the lab of David Gadsby, a very gentle Englishman, known for his pioneering experiments on the sodium pump. Much to my regret he passed away prematurely in 2019. David’s lab was very inspiring, with members from around the world. David sent me to Don Hilgemann in Dallas for two months where I learnt the “giant patch” technique. With that I could show that a cAMP-dependent anion channel in guinea pig heart cells is activated by protein kinase A and ATP and is equal to the recently cloned human cystic fibrosis transmembrane conductance regulator (CFTR). In New York I also found the love of my life, Anna, a guest professor at Columbia University from Napoli, Italy. Together we enjoyed New York even more and she — as a molecular biologist — helped me to widen my biophysical approach to science. The departure from NY to Germany (and Anna’s to Italy) was hard but fortunately, Anna then came to EMBL in Heidelberg, not too far from Frankfurt where I got a group leader position in Bamberg’s department at the MPI.


With Bamberg I started expression of the light-activated proton pump bacteriorhodopsin (BR) in oocytes of Xenopus laevis. This approach turned out to be quite successful and could have been the beginning of optogenetics in 1995. But the time was not yet ripe. We then characterized more microbial rhodopsins with the oocyte-, and later also mammalian cell-, expression approach. The year 1996 was a special year, as Anna and I married in Denmark and Nina was born. Our daughter presented a new sense to life and a balance to some of the hardships and failures in the lab.


In 1995 Peter Hegemann published chlamyopsin, a gene sequence from the green alga Chlamydomonas reinhardtii, as a hypothetical rhodopsin and possible light-gated ion channel. However, chlamyopsin turned out not to be an ion channel and five years later Peter contacted me when he found Chlamydomonas DNA sequences that showed similarity to BR. Even though expression of the first candidate in oocytes was extremely low, I could show a light-sensitive H+ conductance, so I called the protein channelrhodopsin-1 (2002). With channelrhodopsin-2 (2003) our lab showed a light-induced permeability for mono- and divalent cations, and strong light effects on membrane potential. Obviously, we had discovered a new tool which five labs then independently introduced to neuroscience in 2005/2006. Soon after the discovery of channelrhodopsin-2 we were also the first to show the application of a newly discovered photoactivated adenylyl cyclase for cellular signaling research. In 2004, called to Wuerzburg as professor for Molecular Plant Physiology, I have since learned to know and love the city of my “hospital youth”. In 2019, thanks to the generous hospitality of the chairman of the Neurophysiology Department, Manfred Heckmann, we moved to the Institute of Physiology in the heart of the city, where I feel even more at home.

 

 

20 May 2021   Hong Kong