Optogenetics: Illuminating the Path toward Causal Neuroscience

2019 Warren Alpert Foundation Prize Symposium

In honor of Edward Boyden, Karl Deisseroth, Peter Hegemann, Gero Miesenböck for the development of optogenetics as a way to control the activity of specific circuits in the nervous system, to determine their function and ultimately to control them to treat neurological and psychiatric disorders.

Edward Boyden

Edward Boyden | 2019 Recipient

Edward Boyden is the Y. Eva Tan Professor of Neurotechnology, Professor of Biological Engineering and Brain and Cognitive Sciences at MIT’s Media Lab and McGovern Institute for Brain Research, and Co-Director of the MIT Center for Neurobiological Engineering. In 2018, he was selected to be an Investigator of the Howard Hughes Medical Institute.  While a PhD student at Stanford, he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. In parallel, he co-invented optogenetic control of neurons. In particular, he and co-winner Karl Deisseroth brainstormed about how microbial opsins could be used to mediate optical control of neural activity while both were students. Together, the two of them collaborated to demonstrate the firstoptical control of neural activity using microbial opsins, with Karl, then a postdoc, and Ed, then a graduate student, performing the gene transfection and the optical stimulation respectively.

His lab at MIT pioneered optogenetic neural silencing using microbial opsins, and further developed the optogenetic toolset towards the neuroscience-driven goals of powerful, noninvasive, high-speed, multiplexed, and single-cell targeted optical control of neural activity. Dr. Boyden has received the Grete Lundbeck Brain Prize (2013), the Jacob Heskel Gabbay Award (2013), the Carnegie Prize in Mind and Brain Sciences (2015), the BBVA Foundation Frontiers of Knowledge Award (2015), the Breakthrough Prize in Life Sciences (2016), and the Canada Gairdner International Award (2018).  He is an elected member of the National Academy of Sciences, the American Academy of Arts and Sciences, and the National Academy of Inventors.

Karl Deisseroth

Karl Deisseroth | 2019 Recipient

Deisseroth received his AB from Harvard, MD from Stanford, and PhD from Stanford in 1998. He launched his laboratory spanning the Departments of Bioengineering and Psychiatry at Stanford in July 2004, where he and his students created and developed both optogenetics with microbial opsin genes (a technology to control specific neurons with light), and hydrogel-tissue chemistry (which includes CLARITY, STARmap, and many variants—all allowing the transformation of tissues into optically transparent and tractable hydrogel-hybrid forms suitable for high-resolution structural and molecular study). He was elected to the National Academy of Medicine in 2010, National Academy of Sciences in 2012, and National Academy of Engineering in 2019.Twenty-three alumni from his lab have moved on to tenure-track faculty positions (including Feng Zhang and Ed Boyden, the two students on his initial optogenetics paper).

Deisseroth was the sole recipient (for optogenetics) of the 2010 Koetser Prize, 2010 Nakasone Prize, 2013 Lounsbery Prize, 2014 Dickson Prize in Science, 2015 Keio Prize, 2015 Lurie Prize, 2015 Albany Prize, 2015 Dickson Prize in Medicine, 2017 Redelsheimer Prize, 2017 Fresenius Prize, 2018 Eisenberg Prize, and 2018 Kyoto Prize. For his discoveries, Deisseroth has also received the NIH Director’s Pioneer Award (2005), Zuelch Prize (2012), Perl Prize (2012), BRAIN Prize (2013), Pasarow Prize (2013), Breakthrough Prize (2015), Gabbay Prize (2015), BBVA Award (2016), Massry Prize (2016) and Harvey Prize from the Technion in Israel (2017).

Peter Hegemann

Peter Hegemann | 2019 Recipient

Peter Hegemann is a Hertie professor for neuroscience and head of Experimental Biophysics at Humboldt-Universitaet zu Berlin. Hegemanns research focused almost entirely on the characterization of natural sensory photoreceptors. Hegemann has characterized behavioral and photoelectric responses of the unicellular alga Chlamydomonas, a work that cumulated in the claim that the photoreceptors for these responses a rhodopsins that unify the sensor and ion channel in one protein. He has finally proven this concept by identifying the light gated channel channelrhodopsin, and its functionality in animal cells.

His group characterized this protein in molecular detail by a wide range of biophysical techniques; in close collaboration with Karl Deisseroth this lead to the deciphering of the ion channel mechanism, including gating and ion selection. This work was the basis for the discovery of Optogenetics, a technology where light activated proteins – first of all channelrhodopsin - allow to control selected cells of large networks as the animal brain with unprecedented precision in space and time just by application of light. The Hegemann group also works on light-activated enzymes which further expand the optogenetic applications to important biochemical pathways.

Gero Miesenböck

Gero Miesenböck | 2019 Recipient

Gero Miesenböck is Waynflete Professor of Physiology and founding Director of the Centre for Neural Circuits and Behaviour at the University of Oxford. Before coming to Oxford in 2007, he held faculty appointments at Memorial Sloan-Kettering Cancer Center and Yale University. Miesenböck was the first scientist to modify neurons genetically so that their electrical activity could be controlled with light. This involved inserting DNA for light-responsive opsin proteins into the cells. He used similar genetic modifications to breed animals whose brains contained light-responsive neurons integrated into their circuitry and was the first to demonstrate that the behavior of these animals could be remote-controlled. Miesenböck has received many awards for the invention of optogenetics, including the InBev-Baillet Latour International Health Prize, the Brain Prize, the Heinrich Wieland Prize, the BBVA Foundation Frontiers of Knowledge Award, and the Massry Prize. He is a member of the Austrian and German Academies of Sciences and a Fellow of the Royal Society.

Symposium Program

Each year the recipient(s) of the Warren Alpert Foundation Prize are recognized at a scientific symposium hosted by Harvard Medical School.

Featured Speakers include:

Edward Boyden, PhD

Y. Eva Tan Professor in Neurotechnology MIT Media Lab and McGovern Institute Investigator, Howard Hughes Medical Institute

Karl Deisseroth, MD, PhD

D.H. Chen Professor of Bioengineering and Psychiatry Stanford University Investigator, Howard Hughes Medical Institute

Peter Hegemann, PhD

Hertie Professor for Neuroscience and Head of Experimental Biophysics Humboldt-Universität zu Berlin

Gero Miesenböck, FRS

Waynflete Professor of Physiology and Founding Director of the Centre for Neural Circuits and Behaviour University of Oxford

Invited Speakers Include:

Charlotte Arlt, PhD

Postdoctoral Research Fellow, Department of Neurobiology Harvard Medical School

Kimberly Reinhold, PhD

Postdoctoral Research Fellow, Department of Neurobiology Harvard Medical School

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I would like to express my sincere appreciation to the Warren Alpert Foundation and Harvard Medical School for awarding me such a great honor. For me, this award is not only an honor but a responsibility.
- Tu Youyou

Tu Youyou | 2015 Recipient

For their pioneering discoveries in chemistry and parasitology, and personal commitments to translate these into effective chemotherapeutic and vaccine-based approaches to control malaria - their collective work will impact millions of lives globally particularly in the developing countries.

Tu Youyou is currently a Professor and Director of Qinghaosu Research Center at Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences.

Tu joined the Institute of Chinese Materia Medica (ICMM), China Academy of Traditional Chinese Medicine (CATCM) (renamed China Academy of Chinese Medical Sciences, CACMS in 2005) in 1955 after graduation from School of Pharmacy, Beijing Medical College (1951 – 1955).  She late attended a two and half year course on the traditional Chinese medicine (TCM) (1959-1962) - an in depth training specifically designed and offered to the graduates with Western medical background.  Over more than forty years, Tu has been working in the institute as a research assistant, assistant professor, associate professor, professor and director of the Chemistry Department.  She also holds a chief professor position of CACMS as well as members of Phytochemistry Society of China Pharmaceutical Association; Chinese Society of Traditional and Natural Drugs; Council member and Founding Member of Chinese Association of Invention; Executive Committee of All-China Women's Federation (1988-93) and a committee member of Beijing Committee of Natural Science Foundation (1995-97).

Tu’s research on anti-malaria drugs started in 1969 when she was appointed to head the Project 523 research group at the institute.  Project 523 was a secret military program initiated by the Chinese leadership in 1967 in supporting Vietnam government for searching medicines to treat anti chloroquine-resistant malaria.  Tremendous efforts had been made both in US and China but no effective drugs were found by the time Tu accepted the task.

Tu started with collection of over 2000 candidate recipes from which she and her team later screened over hundreds of herbal extracts.  Only one of the extracts from Qinghao (Artemisia annua L.) showed some promising effect, which however was not consistent and reproducible.  Tu further reviewed all available tradition Chinese medicine literatures and noticed a paragraph “Take a handful of Qinghao, soak in two liters of water, strain the liquid, and drink” in the Handbook of Prescriptions for Emergencies (340 CE) authored by Ge Hong.  She realized that the heating applied during extraction might have damaged the active components in the herb.  With this in mind, Tu re-designed low temperature extraction approaches using the solvents with low boiling points.  On the 4th October 1971, a neutral ether extract numbered 191 was found 100% effective in clearing Plasmodia in the mice and monkey test models.  To prove safety of the Qinghao extract and expedite the project, Tu and other two colleagues volunteered in the toxicity study on themselves in July 1972.  Between August and October 1972, Tu and her team carried out the first clinical trial in southern China in which all thirty-one patients treated with the Qinghao extract recovered from the disease.  Subsequent to the first clinical trial, Tu and her colleagues further purified the extract and obtained a pure active crystalline in November 1972.  The compound was late named Qinghaosu (Artemisinin).

Over last several decades, Tu has continued her effort in fighting against malaria.  She and her colleagues developed artemisinin into a medicine and late the team further developed dihydro-artemisinin, another anti-malaria drug, which is ten fold more effective than artemisinin itself.

Tu’s achievement in the discovery of artemisinin and its application in the malaria treatment as well as her unanimous contribution to the healthcare of human being have been well recognized nationally and internationally.  She was honored the Lasker ~ Debakey Clinical Medical Research Award in 2011.  Tu also received numerous awards nationally which include “Award for Progress in Anti-malarial Research Achieved by Project 523 Scientific Team” honored by China National Congress of Science and Technology (1978); “National Scientific Discovery Award” for Anti-malaria Drug-Qinghaosu by the China Ministry of Science and Technology (1979); “Invention Award” (as the first inventor) by China National Congress for Awards in Science and Technology (1982); “Award of Young and Middle-aged Experts with Outstanding Contribution” by the Chinese Government (1984); “The Top Honorary Award” by China Academy of Traditional Chinese Medicine (1992); “The Top Ten National Achievements for Progress in Science and Technology” by China National Committee of Science and Technology (1992); “First-Class Award of National Achievements in Science and Technology” by China National Award Committee for Advances in Science and Technology (1992); “National Model” by China State Council (1995); “Award for Outstanding Achievement in Traditional Chinese Medicine” by Guangzhou Zhongjing Award Foundation for Traditional Chinese Medicine (1995); “Outstanding Scientific Achievement Award” by Qiu Shi Science and Technologies Foundation of Hong Kong (1996); “Top Ten Health Achievements in New China” by China Ministry of Health (1997); “Female Inventor of the New Century” by China National Bureau of Intellectual Property (2002); “Golden Medal of the 14th National Invention Exhibition” by China National Bureau of Intellectual Property (2003); “Award for Development of Chinese Materia Medica” by Cyrus Chung Ying Tang Foundation, (2009).  She also received “Prince Mahidol Award” by Thailand Prince Mahidol Award Foundation (2003),  “GlaxoSmithKline Award for Outstanding Achievements in Life Science” (2011), Lasker~DeBakey Clinical Medical Research Award(2011), and the Nobel Prize in Physiology or Medicine(2015).

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