Peter Hegemann

Last updated

Peter Hegemann
Peter Hegemann.jpg
Hegemann receiving the Hertie Senior Research Chair Professorship for Neurosciences in 2015
Born(1954-12-11)11 December 1954 [1]
Münster
Germany [1]
Alma mater Max Planck Institute of Biochemistry
Ludwig Maximilian University of Munich
University of Münster
Known forDiscovery of channelrhodopsin
Children3
Awards Louisa Gross Horwitz Prize
Albert Lasker Award for Basic Medical Research
Shaw Prize in Life Science and Medicine
Warren Alpert Foundation Prize
Rumford Prize
Canada Gairdner International Award
Otto Warburg Medal
Harvey Prize
Massry Prize
The Brain Prize
Louis-Jeantet Prize for Medicine
Gottfried Wilhelm Leibniz Prize
Wiley Prize in Biomedical Sciences
Scientific career
Fields Biophysics
Optogenetics
Institutions Humboldt University of Berlin
University of Regensburg
Max Planck Institute of Biochemistry
Syracuse University
Thesis Halorhodopsin, die lichtgetriebene Chloridpumpe in Halobacterium halobium: Untersuchungen zur Struktur und Funktion  (1984)
Doctoral advisor Dieter Oesterhelt [2]

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.

Contents

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

Related Research Articles

<span class="mw-page-title-main">Behavioral neuroscience</span> Field of study

Behavioral neuroscience, also known as biological psychology, biopsychology, or psychobiology, is the application of the principles of biology to the study of physiological, genetic, and developmental mechanisms of behavior in humans and other animals.

Channelrhodopsins are a subfamily of retinylidene proteins (rhodopsins) that function as light-gated ion channels. They serve as sensory photoreceptors in unicellular green algae, controlling phototaxis: movement in response to light. Expressed in cells of other organisms, they enable light to control electrical excitability, intracellular acidity, calcium influx, and other cellular processes. Channelrhodopsin-1 (ChR1) and Channelrhodopsin-2 (ChR2) from the model organism Chlamydomonas reinhardtii are the first discovered channelrhodopsins. Variants that are sensitive to different colors of light or selective for specific ions have been cloned from other species of algae and protists.

<span class="mw-page-title-main">Photostimulation</span>

Photostimulation is the use of light to artificially activate biological compounds, cells, tissues, or even whole organisms. Photostimulation can be used to noninvasively probe various relationships between different biological processes, using only light. In the long run, photostimulation has the potential for use in different types of therapy, such as migraine headache. Additionally, photostimulation may be used for the mapping of neuronal connections between different areas of the brain by “uncaging” signaling biomolecules with light. Therapy with photostimulation has been called light therapy, phototherapy, or photobiomodulation.

<span class="mw-page-title-main">Halorhodopsin</span> Family of transmembrane proteins


Halorhodopsin is a seven-transmembrane retinylidene protein from microbial rhodopsin family. It is a chloride-specific light-activated ion pump found in archaea known as halobacteria. It is activated by green light wavelengths of approximately 578nm. Halorhodopsin also shares sequence similarity to channelrhodopsin, a light-gated ion channel.

Retinylidene proteins, or rhodopsins in a broad sense, are proteins that use retinal as a chromophore for light reception. They are the molecular basis for a variety of light-sensing systems from phototaxis in flagellates to eyesight in animals. Retinylidene proteins include all forms of opsin and rhodopsin. While rhodopsin in the narrow sense refers to a dim-light visual pigment found in vertebrates, usually on rod cells, rhodopsin in the broad sense refers to any molecule consisting of an opsin and a retinal chromophore in the ground state. When activated by light, the chromophore is isomerized, at which point the molecule as a whole is no longer rhodopsin, but a related molecule such as metarhodopsin. However, it remains a retinylidene protein. The chromophore then separates from the opsin, at which point the bare opsin is a retinylidene protein. Thus, the molecule remains a retinylidene protein throughout the phototransduction cycle.

Light-gated ion channels are a family of ion channels regulated by electromagnetic radiation. Other gating mechanisms for ion channels include voltage-gated ion channels, ligand-gated ion channels, mechanosensitive ion channels, and temperature-gated ion channels. Most light-gated ion channels have been synthesized in the laboratory for study, although two naturally occurring examples, channelrhodopsin and anion-conducting channelrhodopsin, are currently known. Photoreceptor proteins, which act in a similar manner to light-gated ion channels, are generally classified instead as G protein-coupled receptors.

<span class="mw-page-title-main">Gero Miesenböck</span>

Gero Andreas Miesenböck is an Austrian scientist. He is currently Waynflete Professor of Physiology and Director of the Centre for Neural Circuits and Behaviour (CNCB) at the University of Oxford and a fellow of Magdalen College, Oxford.

Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individual cells, light-activated enzymes and transcription factors allow precise control of biochemical signaling pathways. In systems neuroscience, the ability to control the activity of a genetically defined set of neurons has been used to understand their contribution to decision making, learning, fear memory, mating, addiction, feeding, and locomotion. In a first medical application of optogenetic technology, vision was partially restored in a blind patient with Retinitis pigmentosa.

<span class="mw-page-title-main">Edward Boyden</span> American neuroscientist

Edward S. Boyden is an American neuroscientist at MIT. He is the Y. Eva Tan Professor in Neurotechnology, a faculty member in the MIT Media Lab and an associate member of the McGovern Institute for Brain Research. In 2018 he was named a Howard Hughes Medical Institute Investigator. He is recognized for his work on optogenetics. In this technology, a light-sensitive ion channel such as channelrhodopsin-2 is genetically expressed in neurons, allowing neuronal activity to be controlled by light. There were early efforts to achieve targeted optical control dating back to 2002 that did not involve a directly light-activated ion channel, but it was the method based on directly light-activated channels from microbes, such as channelrhodopsin, emerging in 2005 that turned out to be broadly useful. Optogenetics in this way has been widely adopted by neuroscientists as a research tool, and it is also thought to have potential therapeutic applications. Boyden joined the MIT faculty in 2007, and continues to develop new optogenetic tools as well as other technologies for the manipulation of brain activity. Previously, Boyden received degrees in electrical engineering, computer science, and physics from MIT. During high school, Boyden attended the Texas Academy of Mathematics and Science.

<span class="mw-page-title-main">Karl Deisseroth</span> American optogeneticist (born 1971)

Karl Alexander Deisseroth is an American scientist. He is the D.H. Chen Professor of Bioengineering and of psychiatry and behavioral sciences at Stanford University.

<span class="mw-page-title-main">Feng Zhang</span> Chinese–American biochemist

Feng Zhang is a Chinese–American biochemist. Zhang currently holds the James and Patricia Poitras Professorship in Neuroscience at the McGovern Institute for Brain Research and in the departments of Brain and Cognitive Sciences and Biological Engineering at the Massachusetts Institute of Technology. He also has appointments with the Broad Institute of MIT and Harvard. He is most well known for his central role in the development of optogenetics and CRISPR technologies.

<span class="mw-page-title-main">Microbial rhodopsin</span> Retinal-binding proteins

Microbial rhodopsins, also known as bacterial rhodopsins, are retinal-binding proteins that provide light-dependent ion transport and sensory functions in halophilic and other bacteria. They are integral membrane proteins with seven transmembrane helices, the last of which contains the attachment point for retinal.

<span class="mw-page-title-main">Anion-conducting channelrhodopsin</span> Class of light-gated ion channels

Anion-conducting channelrhodopsins are light-gated ion channels that open in response to light and let negatively charged ions enter a cell. All channelrhodopsins use retinal as light-sensitive pigment, but they differ in their ion selectivity. Anion-conducting channelrhodopsins are used as tools to manipulate brain activity in mice, fruit flies and other model organisms (Optogenetics). Neurons expressing anion-conducting channelrhodopsins are silenced when illuminated with light, an effect that has been used to investigate information processing in the brain. For example, suppressing dendritic calcium spikes in specific neurons with light reduced the ability of mice to perceive a light touch to a whisker. Studying how the behavior of an animal changes when specific neurons are silenced allows scientists to determine the role of these neurons in the complex circuits controlling behavior.

Zhuo-Hua Pan is a Chinese-American neuroscientist, known for his foundational contributions to optogenetics. He is the Edward T. and Ellen K. Dryer Endowed Professor of Ophthalmology at Wayne State University, and Scientific Director of the Ligon Research Center of Vision at the university's Kresge Eye Institute.

<span class="mw-page-title-main">Georg Nagel</span>

Georg Nagel is a biophysicist and professor at the Department for Neurophysiology at the University of Würzburg in Germany. His research is focused on microbial photoreceptors and the development of optogenetic tools.

Ernst Bamberg is a German biophysicist and director emeritus of the Department of Biophysical Chemistry at the Max Planck Institute of Biophysics.

<span class="mw-page-title-main">Photoactivated adenylyl cyclase</span>

Photoactivated adenylyl cyclase (PAC) is a protein consisting of an adenylyl cyclase enzyme domain directly linked to a BLUF type light sensor domain. When illuminated with blue light, the enzyme domain becomes active and converts ATP to cAMP, an important second messenger in many cells. In the unicellular flagellate Euglena gracilis, PACα and PACβ (euPACs) serve as a photoreceptor complex that senses light for photophobic responses and phototaxis. Small but potent PACs were identified in the genome of the bacteria Beggiatoa (bPAC) and Oscillatoria acuminata (OaPAC). While natural bPAC has some enzymatic activity in the absence of light, variants with no dark activity have been engineered (PACmn).

Lisa Gunaydin is an American neuroscientist and assistant professor at the Weill Institute for Neurosciences at the University of California San Francisco. Gunaydin helped discover optogenetics in the lab of Karl Deisseroth and now uses this technique in combination with neural and behavioral recordings to probe the neural circuits underlying emotional behaviors.

Alexander Gottschalk is Professor of Cellular and Molecular Neurobiology at the Goethe University in Frankfurt, Germany.

Dieter Oesterhelt was a German biochemist. From 1980 until 2008, he was director of the Max Planck Institute for Biochemistry, Martinsried.

References

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