German biophysicist
Peter Hegemann (born 11 December 1954) is a Hertie Senior Research Chair for Neurosciences and a professor of Experimental Biophysics at the Department of Biology , Faculty of Life Sciences , Humboldt University of Berlin , Germany.[ 3] [ 4] He is known for his discovery of channelrhodopsin , a type of ion channels regulated by light , thereby serving as a light sensor. This created the field of optogenetics , a technique that controls the activities of specific neurons by applying light. He has received numerous accolades, including the Rumford Prize , the Shaw Prize in Life Science and Medicine , and the Albert Lasker Award for Basic Medical Research .
Early life and education
Hegemann was born in Münster in 1954, but grew up in Aachen .[ 5] Many in his immediate and extended family are doctors, including his parents, brother, and both grandfathers. He was educated in a humanities-oriented gymnasium (humanistisches Gymnasium ) for secondary school, which he disliked for his lack of interest in classical studies .[ 5] He liked science subjects and was at first interested in discovery of new territories and then in the outer space . Eventually, he went to the University of Münster in 1975 to study chemistry , transferring to the Ludwig Maximilian University of Munich two years later to switch to biochemistry .[ 5]
After graduating in 1980, Hegemann pursued his PhD at the Max Planck Institute of Biochemistry in the research group of Dieter Oesterhelt ,[ 5] who has just become the Director of the institute.[ 6] He completed it in 1984.[ 7]
Career
Having won a fellowship for his PhD thesis, Hegemann went to Syracuse University in 1985 as a postdoctoral fellow in Kenneth W. Foster's lab for a year. After returning to Germany, he was offered a five-year position as a principal investigator at the Max Planck Institute of Biochemistry .[ 8]
In 1993, Hegemann joined the Department of Biochemistry of the University of Regensburg as a professor. He moved to the Humboldt University of Berlin in 2004 and became a professor of Experimental Biophysics .[ 7] In 2015, he was endowed with a Hertie Senior Research Chair for Neurosciences.[ 9]
Research
Hegemann's research into light-gated ion transport began in his PhD years, when he investigated the structure and function of halorhodopsin , an active ion transporter found in a type of archaea called haloarchaea that uses light energy to move chloride ions against the gradient.[ 10] [ 11] As part of his PhD project, he characterized this protein in Halobacterium salinarum , discovering that yellow light activates halorhodopsin.[ 12] [ 13] When halorhodopsin is expressed in neurons and activated by light, the influx of chloride ions shifts the neuron to more negative electric potential , preventing action potential generation and inactivating the neurons.[ 14]
A 1984 article by Kenneth W. Foster of Syracuse University suggested that rhodopsins would also serve as light detector in the green alga Chlamydomonas reinhardtii .[ 15] This also prompted Hegemann to spend a year with Foster as a postdoctoral fellow .[ 16] Hegemann continued characterizing this rhodopsin after returning to Germany. Working on another green alga, he found that it had a fast electrical response (by ion movement through ion channel ) to light stimulation, and proposed that the ion channel and the light-detecting rhodopsin were one single protein complex .[ 17] [ 18] [ 19]
In 2002, collaborating with Georg Nagel and Ernst Bamberg , Hegemann made the landmark identification of the gene for this rhodopsin and named it Channelrhodopsin-1 .[ 20] The team identified the second channelrhodopsin gene, Channelrhodopsin-2 , the next year.[ 21] In both studies, they cloned the genes from Chlamydomonas reinhardtii and expressed them in the oocytes of African clawed frog . Upon blue light stimulation, electrical currents was detected in the oocytes.[ 22] When channelrhodopsins are expressed in neurons and stimulated, the ion channel opens so positively charged calcium and sodium ions can enter the neurons, creating a more positive electric potential inside the neurons and activating them. This is the opposite effect of halorhodopsin activation.[ 23]
The field of optogenetics took off from these discoveries. In 2005, Hegemann reported expressing channelrhodopsin in chicken embryos , their movement can be controlled with light stimulation.[ 24] This came in the same year as another study by a collaboration between Karl Deisseroth , Edward Boyden , Feng Zhang , Georg Nagel and Ernst Bamberg, which found light could lead to action potential in cultured neurons expressing channelrhodopsin.[ 25] Teaming up with Deisseroth, Hegemann continued advancing optogenetics by developing rhodopsin variants that could react faster and more accurately,[ 26] detect different wavelengths of light [ 27] and conduct different ions.[ 28] [ 29]
Using optogenetic techniques, Hegemann and collaborators have confirmed that the unbalanced activity of excitatory and inhibitory neurons causes behavioral deficits of mental disorders .[ 30]
Honours and awards
References
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^ "A curious color change" . Cell . 184 (21): 5286– 5288. 2021. doi :10.1016/j.cell.2021.08.011 . PMID 34562366 . S2CID 237622462 .
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^ Kolbe, Michael; Besir, Hüseyin; Essen, Lars-Oliver; Oesterhelt, Dieter (2000). "Structure of the Light-Driven Chloride Pump Halorhodopsin at 1.8 Å Resolution" . Science . 288 (5470): 1390– 1396. Bibcode :2000Sci...288.1390K . doi :10.1126/science.288.5470.1390 . PMID 10827943 . Retrieved 15 December 2022 .
^ "Halorhodopsin" . Max Planck Institute of Biochemistry. Archived from the original on 16 December 2022. Retrieved 16 December 2022 .
^ Bamberg, E. ; Hegemann, P.; Oesterhelt, D. (1984). "The chromoprotein of halorhodopsin is the light-driven electrogenic chloride pump in Halobacterium halobium" . Biochemistry . 23 (24): 6216– 6221. doi :10.1021/bi00320a050 . PMID 24409552 . Retrieved 17 December 2022 .
^ Hegemann, P.; Oesterhelt, D.; Steiner, M. (1985). "The photocycle of the chloride pump halorhodopsin. I: Azidecatalyzed deprotonation of the chromophore is a side reaction of photocycle intermediates inactivating the pump" . The EMBO Journal . 4 (9): 2347– 2350. doi :10.1002/j.1460-2075.1985.tb03937.x . PMC 554508 . PMID 15938053 .
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^ Foster, Kenneth W.; Saranak, Jureepan; Patel, Nayana; Zarilli, Gerald; Okabe, Masami; Kline, Toni; Nakanishi, Koji (1984). "A rhodopsin is the functional photoreceptor for phototaxis in the unicellular eukaryote Chlamydomonas " . Nature . 311 (5988): 756– 759. Bibcode :1984Natur.311..756F . doi :10.1038/311756a0 . PMID 649333 . S2CID 4263301 . Retrieved 18 December 2022 .
^ Neuman, Nicole (2021). "Unexpected pairings" . Cell . 184 (21): 5289– 5292. doi :10.1016/j.cell.2021.08.009 . PMID 34562361 .
^ Braun, Franz-Josef; Hegemann, Peter (1999). "Two Light-Activated Conductances in the Eye of the Green Alga Volvox carteri " . Biophysical Journal . 76 (3): 1668– 1678. Bibcode :1999BpJ....76.1668B . doi :10.1016/S0006-3495(99)77326-1 . PMC 1300143 . PMID 10049347 .
^ Conti, Lisa R. (2021). "Karl Deisseroth, Peter Hegemann, and Dieter Oesterhelt receive the 2021 Albert Lasker Basic Medical Research Award" . Journal of Clinical Investigation . 131 (19): e154418. doi :10.1172/JCI154418 . PMC 8483750 . PMID 34558419 .
^ Hegemann, Peter; Nagel, Georg (2013). "From channelrhodopsins to optogenetics" . EMBO Molecular Medicine . 5 (2): 173– 176. doi :10.1002/emmm.201202387 . PMC 3569634 . PMID 23339069 .
^ Nagel, Georg; Ollig, Doris; Fuhrmann, Markus; Kateriya, Suneel; Musti, Anna Maria; Bamberg, Ernst; Hegemann, Peter (2002). "Channelrhodopsin-1: A Light-Gated Proton Channel in Green Algae" . Science . 296 (5577): 2395– 2398. Bibcode :2002Sci...296.2395N . doi :10.1126/science.1072068 . PMID 12089443 . S2CID 206506942 . Retrieved 21 December 2022 .
^ Nagel, Georg; Szellas, Tanjef; Huhn, Wolfram; Kateriya, Suneel; Adeishvili, Nona; Berthold, Peter; Ollig, Doris; Hegemann, Peter; Bamberg, Ernst (2003). "Channelrhodopsin-2, a directly light-gated cation-selective membrane channel" . Proceedings of the National Academy of Sciences . 100 (24): 13940– 13945. Bibcode :2003PNAS..10013940N . doi :10.1073/pnas.1936192100 . PMC 283525 . PMID 14615590 .
^ Friedman, Jeffery M. (2021). "How the discovery of microbial opsins led to the development of optogenetics" . Cell . 184 (21): 5266– 5270. doi :10.1016/j.cell.2021.08.022 . PMID 34562360 . S2CID 237622465 .
^ Häusser, Michael (2021). "Optogenetics – The Might of Light" (PDF) . The New England Journal of Medicine . 385 (17): 1623– 1626. doi :10.1056/NEJMcibr2111915 . PMID 3456973 . S2CID 237941581 . Archived from the original (PDF) on 22 December 2022. Retrieved 24 December 2022 .
^ Li, Xiang; Gutierrez, Davina V.; Hanson, M. Gartz; Han, Jing; Mark, Melanie D.; Chiel, Hillel; Hegemann, Peter; Landmesser, Lynn T. ; Herlitze, Stefan (2005). "Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin" . Proceedings of the National Academy of Sciences . 102 (49): 17816– 17821. Bibcode :2005PNAS..10217816L . doi :10.1073/pnas.0509030102 . PMC 1292990 . PMID 16306259 .
^ Boyden, Edward S. ; Zhang, Feng ; Bamberg, Ernst; Nagel, Georg; Deisseroth, Karl (2005). "Millisecond-timescale, genetically targeted optical control of neural activity" . Nature Neuroscience . 8 (9): 1263– 1268. doi :10.1038/nn1525 . PMID 16116447 . S2CID 6809511 . Retrieved 28 December 2022 .
^ Gunaydin, Lisa A. ; Yizhar, Ofer; Berndt, André; Sohal, Vikaas S.; Deisseroth, Karl; Hegemann, Peter (2010). "Ultrafast optogenetic control" (PDF) . Nature Neuroscience . 13 (3): 387– 392. doi :10.1038/nn.2495 . PMID 20081849 . S2CID 7457755 . Archived from the original (PDF) on 5 December 2022. Retrieved 5 December 2022 .
^ Zhang, Feng; Prigge, Matthias; Beyrière, Florent; Tsunoda, Satoshi P.; Mattis, Joanna; Yizhar, Ofer; Hegemann, Peter; Deisseroth, Karl (2008). "Red-shifted optogenetic excitation: a tool for fast neural control derived from Volvox carteri" . Nature Neuroscience . 11 (6): 631– 633. doi :10.1038/nn.2120 . PMC 2692303 . PMID 18432196 .
^ Wietek, Jonas; Wiegert, J. Simon; Adeishvili, Nona; Schneider, Franziska; Watanabe, Hiroshi; Tsunoda, Satoshi P.; Vogt, Arend; Elstner, Marcus; Oertner, Thomas G.; Hegemann, Peter (25 April 2014). "Conversion of Channelrhodopsin into a Light-Gated Chloride Channel" . Science . 344 (6182): 409– 412. Bibcode :2014Sci...344..409W . doi :10.1126/science.1249375 . ISSN 0036-8075 . PMID 24674867 .
^ Fernandez Lahore, Rodrigo G.; Pampaloni, Niccolò P.; Schiewer, Enrico; Heim, M.-Marcel; Tillert, Linda; Vierock, Johannes; Oppermann, Johannes; Walther, Jakob; Schmitz, Dietmar; Owald, David; Plested, Andrew J. R.; Rost, Benjamin R.; Hegemann, Peter (21 December 2022). "Calcium-permeable channelrhodopsins for the photocontrol of calcium signalling" . Nature Communications . 13 (1): 7844. Bibcode :2022NatCo..13.7844F . doi :10.1038/s41467-022-35373-4 . ISSN 2041-1723 . PMC 9772239 . PMID 36543773 .
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