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Multicomponent Optogenetics - Sensing is not Understanding

CMCB Life Sciences Seminar

Date:10.10.2019, 16:00 - 17:00
Speaker: Prof. Peter Hegemann, Humboldt-Universität zu Berlin
Location: CRTD, ground floor, auditorium left
Host: Prof. Francis Stewart (BIOTEC)

Abstract:

Activation or inactivation of a living cell, tissue or animal, either naturally or artificially, initiates small or larger long-term changes within the living system (The biological uncertainty principle). In most cases the researcher intends to learn about the living system without being aware about its own – in many cases -destructive  action. Illumination of a cell is probably one the least destructive action one may undertake. We study natural sensory photoreceptors mostly from green algae with respect to the original function within the algal context but also modify these photoreceptors and employ them in host cells to mani-pulate host processes ideally non-invasively. For a long time the membrane voltage has been the main host parameter and we engineered - supported by spectroscopic and structural information - light-gated channels and light-driven pumps in many direction with respect to color sensing, ion selectivity and kinetics, and converted ion pumps into ion channels or vice versa to understand the principle differences. More recently we focused on second messengers as cAMP and cGMP by employment of fungal photo-activated cyclases. The combi¬nation with cyclic nucleotide gated (cNG) channels generated multi-component optogenetic systems with large amplifications providing ultra high sensitivity in host cells.  We keep in mind Max Plancks concept: “Understanding precedes application” and we begin to learn that “manipulation always causes distraction from natural behavior”. Moreover, large signals do not mean natural responses, it may be just the opposite.

5 most important publications:

1.* Harz, H. and Hegemann, P. (1991) Rhodopsin-regulated calcium currents in Chlamydomonas. Nature 351, 489-491.
2.* Nagel, G., Ollig, D., Fuhrmann, M., Kateriya, S., Musti, A.-M., Bamberg, E., Hegemann, P. (2002) Channelrhodopsin-1, a light-gated proton channel in green algae. Science 296, 2395 - 2398.
3.* Stierl, M., Stumpf, P., Udwari, D., Gueta, R., Hagedorn, R., Losi, A., Gärtner, W., Petereit, L., Efetova, M., Schwarzel, M., Oertner, T.G., Nagel, G., and Hegemann, P. (2011) Light-modulation of cellular cAMP by a small bacterial photoactivated adenylyl cyclase, bPAC, J. Biol. Chem. 286: 1181-1188.  
4.* Wietek, J., Wiegert, J.S., Adeishvili, N., Schneider, F., Watanabe, H., Tsunoda, S.P., Vogt, A., Elstner, M., Oertner, T.G., Hegemann, P. (2014) Conversion of Channelrhodopsin into a light-gated chloride channel. Science 344, 409 – 412.
5. * Scheib, U., Stehfest, K., Gee, C. E., Körschen, H.G., Fudim, R., Oertner, T. G., and Hegemann, P. (2015) The rhodopsin-guanylyl cyclase of the aquatic fungus Blastocladiella emersonii enables fast optical control of cGMP signaling. Science Signaling 8, 389 rs8.

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