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2019 Warren Alpert Foundation Award goes to Four Scientists for Seminal Discoveries in OptoGenetics – Illuminating the Human Brain
Reporter: Aviva Lev-Ari, PhD, RN
@AVIVA1950
@phharma_BI
Optogenetics, a revolutionary technique that uses light and genetic modification to control the activity of cells in the brain.
Each year the recipient(s) of the Warren Alpert Foundation Prize are recognized at a scientific symposium hosted by Harvard Medical School.
2019 WARREN ALPERT FOUNDATION PRIZE SYMPOSIUM
Optogenetics: Illuminating the Path toward Causal Neuroscience
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.
Moderated by
- Bernardo Sabatini, MD, PhD, Professor of Neurology, HMS
Cells in the brain studied by opto-genetics for treatment of neuropsychiatric disorders
Opening Remarks
- George Q. Daley, Dean, Harvard Medical School
Featured Speakers Include:
Edward Boyden, PhD – In honor of and Speaker
Y. Eva Tan Professor in Neuro technology
MIT Media Lab and McGovern Institute
Investigator, Howard Hughes Medical Institute
- microbial opsins binding endogenuous all-trans-retinal
- search locally in genomics space: sensitivity to ArchT
- In response to yellow light vs red light
- Map the molecules, wiring and connections
Karl Deisseroth, MD, PhD – In honor of and Speaker
D.H. Chen Professor of Bioengineering and Psychiatry
Stanford University
Investigator, Howard Hughes Medical Institute
- Channelrhodopsins – Inner workings of – light-dated pores
- Diverse modes of designed photon-spike logic, ion selectivity, color tuning – ANION-conducting ChRs
- microbial opsin genesMolecular biology on neuroscience
- neurol codes of behavior
- Identification of feeding-responsive OFC cells
- activity-guided optogenetic stimulation: social interaction vs self feeding
- Time spent licking – all-optical Read/Write across cortical layers: L2/3 through
- Stimulation: Visual stimuli vs Optogenetic stimuli vs Ensemble-specific stimulation: Tuned vs Random
- Unstimulated population dynamics – visually-evoked vs stimulated popualtion using Classifier – discrimination behavior
- Number stimulated neurons: Laminar population recruitment corresponds to behavior
- neuronal activity during task performance: Thirst-motivated behavior
- Epigenetics: Optogenetic stimulation restores
Peter Hegemann, PhD – In honor of and Speaker
Hertie Professor for Neuroscience and Head of Experimental Biophysics
Humboldt-Universität zu Berlin
- Optogrnetic excitation
- channel-rhodopsin (ChR) during MD calculation, intracellulat and extracellular sideCentral gate Inner gate
- all-trans
- elements of light switch
- Improved Na+ over H+ sensitivity
- outer pore constriction – K-channels hyper polarization n neuroscience
- PAC-K silencing of vertical cardiocytes
- Optogenetic Actuators
Gero Miesenböck, FRS – In honor of and Speaker
Waynflete Professor of Physiology and Founding Director of the Centre for Neural Circuits and Behavior
University of Oxford
- Asleep vs Awake electrically active vs silent signals
- Dopamine and arousal – OFF/ON of the dopaminergic system
- operating the sleep switch
- mechanisms: Sleep-Control Neurons current vs membrane potential
- What is the biologic process of switch in sleep? it is: A voltage-controlled oxidoreductase OR a
- redux-controlled ion channel
- Mitochondrial Electron Transport in the matrix membrane: NADPH – The missing link: NADH>NAD+, O2>O2- O2>H2O ADP>ATPm- mitoTimer
- redox changes accompany changes in sleep pressure: Sleep-deprived vs Rested
- Perturbing the Redox Chemistry of dFB – AOX = PUFAs – 4-OXO~2~nonenal
- Flipping the Redox Switch Promotes Sleep
- Redox sensing by Hyperkinetics regulates the activity of dFB Neurons
Invited Speakers Include:
Charlotte Arlt, PhD, Speaker
Postdoctoral Research Fellow, Department of Neurobiology
Harvard Medical School
- Virtual reality in decision making: Left or right
- GABAergic neuron ChR2+Photostimulation vs no photostimulation
- identical decisions in different context
- The brain persists using same areas weeks after trained in simple context
- Flexible environments
- simple context: Brain areas used in flexible decisions
Kimberly Reinhold, PhD, Speaker
Postdoctoral Research Fellow, Department of Neurobiology
Harvard Medical School
- Trial and erroe learning – impaired in Parkinsosn’s
- episodic learning: Amnesia impaired
- Pathwat in Basal ganglia: Cortex-Striatum optogenetic cue to achieve motor output
- Action potential recorded neural activity to disengage the striatum: Output neuron – inhibitory neuronspatially and temporality loss function – mice perform cued reaches despite
- striatum does not trigger cues – needed during learning
- measuring learning for reinforced learning – non cues reached within a day
- inhibiting the Striatum impede learning it is not needed after learning
- Behavior space: healhty learning VS Parkinson’s, PTSD and other
Closing Remarks
George Q. Daley, Dean, Harvard Medical School
Location:
Joseph B. Martin Conference Center, New Research Building
Harvard Medical School
77 Avenue Louis Pasteur, Boston
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Optogenetic manipulation of degenerating or aberrant neural circuits in the human brain carries the promise to
- restore vision loss,
- Alterations in Gait i.e., Parkinson’s Disease
- preserve movement following spinal cord injury, or
- dampen down circuits that fuel anxiety, depression and other psychiatric conditions (i.e., addictions).
“The 2019 Warren Alpert Prize for medical research recognizes one of the transformative technical advances of the past decade. The ability to selectively turn on neuronal signals with light exposure has made achievable a more refined analysis of neural connections underlying behavior,” said Joseph Martin, director and chairman of the board of the Warren Alpert Foundation and former dean of Harvard Medical School.
The Warren Alpert Foundation in association with Harvard Medical School
Each year the Warren Alpert Foundation receives between 30 and 50 nominations from scientific leaders worldwide. Prize recipients are selected by the foundation’s scientific advisory board, which is composed of distinguished biomedical scientists and chaired by the dean of Harvard Medical School.
Warren Alpert (1920-2007), a native of Chelsea, Mass., established the prize in 1987 after reading about the development of a vaccine for hepatitis B. The inaugural recipient of the award was Kenneth Murray of the University of Edinburgh, who designed the hepatitis B vaccine. To award subsequent prizes, Alpert asked Daniel Tosteson (1925-2009), then dean of Harvard Medical School, to convene a panel of experts to identify scientists from around the world whose research had a direct impact on the treatment of disease.
Past winners
Last year’s award went to five scientists for transformative discoveries in the fields of genetics, physiology, pulmonology and pharmacology that led to the development of life-altering precision-targeted treatments for the devastating multiorgan disease cystic fibrosis. They were Francis Collins, Paul Negulescu, Bonnie Ramsey, Lap-Chee Tsui, Michael Welsh.
Other past recipients of the Warren Alpert award include:
• James Allison, Lieping Chen, Gordon Freeman, Tasuku Honjo and Arlene Sharpe for discoveries into cancer’s ability to evade immune surveillance that led to the development of a class of cancer immunotherapies.
• Rodolphe Barrangou, Emmanuelle Charpentier, Jennifer Doudna, Philippe Horvath and Virginijus Siksnys for CRISPR-related discoveries.
• Tu Youyou, who went on to receive the 2015 Nobel Prize in Physiology or Medicine with two others, and Ruth and Victor for their pioneering discoveries in the chemistry and parasitology of malaria and the translation of that work into the development of drug therapies and an antimalarial vaccine.
• Oleh Hornykiewicz, Roger Nicol, and Solomon Snyder for research into neurotransmission and neurodegeneration.
• Alain Carpentier for innovations in bioengineering.
• Harald zur Hausen and Lutz Gissmann for work on the human papillomavirus (HPV) and its role in cervical cancer. Zur Hausen and others were honored with the Nobel Prize in Physiology or Medicine in 2008.
The honorees will share a $500,000 prize and will be recognized at a daylong symposium on Oct. 3 at Harvard Medical School.
The 2019 Warren Alpert Foundation Prize recipients are:
• Edward Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT, associate professor of media arts and sciences at the MIT Media Lab and an investigator at the McGovern Institute for Brain Research at MIT, for his insight in leveraging natural biomolecules for the manipulation and understanding of neuronal and brain function, which established and deployed the tools needed for optogenetics.
• Karl Deisseroth, the D.H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University, for establishing the modern field of optogenetics, for rendering the technique an invaluable tool for biological discovery, and for discovering along with Peter Hegemann the key principles of light-sensitive channel structure and function.
• Peter Hegemann, the Hertie professor of Neuroscience at Humboldt University of Berlin, for his study of light-sensitive molecular channels in single-cell organisms—the key proteins that make optogenetic manipulation possible—and discovering along with Karl Deisseroth the key principles of light-sensitive channel structure and function.
• Gero Miesenböck, the Waynflete Professor of Physiology and director of the Centre for Neural Circuits and Behaviour at the University of Oxford in the United Kingdom, for the first demonstrations of optogenetic control of neural activity and animal behavior and for discoveries proving the utility of optogenetics for neurobiological research
“The discoveries made by this year’s four honorees have fundamentally changed the landscape of neuroscience,” said George Q. Daley, dean of Harvard Medical School. “Their work has enabled scientists to see, understand and manipulate neurons, providing the foundation for understanding the ultimate enigma—the human brain.”
The Warren Alpert Foundation Prize recognizes the work of scientists throughout the world. To date, the Warren Alpert Foundation Prize has awarded nearly $5 million to 69 scientists. Since the award’s inception in 1987, 10 honorees have gone on to receive a Nobel Prize.
SOURCE
https://warrenalpert.org/news/2019-warren-alpert-prize-recipients-announced
Ed Boyden receives 2019 Warren Alpert Prize – MIT McGovern Institute
Ed Boyden holds the titles of
- Investigator, McGovern Institute;
- Y. Eva Tan Professor in Neurotechnology at MIT;
- Leader, Synthetic Neurobiology Group, Media Lab;
- Associate Professor, Biological Engineering, Brain and Cognitive Sciences, Media Lab;
- Co-Director, MIT Center for Neurobiological Engineering;
- Member, MIT Center for Environmental Health Sciences,
- Member Computational and Systems Biology Initiative, and Koch Institute.
“It is truly an honor to be included among the extremely distinguished list of winners of the Alpert Award,” says Boyden, the Y. Eva Tan Professor in Neurotechnology at the McGovern Institute, MIT. “To me personally, it is exciting to see the relatively new field of neurotechnology recognized. The brain implements our thoughts and feelings. It makes us who we are. This mysteries and challenge requires new technologies to make the brain understandable and repairable. It is a great honor that our technology of optogenetics is being thus recognized.”
While they were students, Boyden, and fellow awardee Karl Deisseroth, brainstormed about how microbial opsins could be used to mediate optical control of neural activity. In mid-2004, the pair collaborated to show that microbial opsins can be used to optically control neural activity.
Upon launching his lab at MIT, Boyden’s team developed the
- first optogenetic silencing tool,
- the first effective optogenetic silencing in live mammals,
- noninvasive optogenetic silencing, and
- single-cell optogenetic control.
“The discoveries made by this year’s four honorees have fundamentally changed the landscape of neuroscience,” said George Q. Daley, dean of Harvard Medical School. “Their work has enabled scientists to see, understand and manipulate neurons, providing the foundation for understanding the ultimate enigma—the human brain.”
Beyond optogenetics, Boyden has
- pioneered transformative technologies that image, record, and manipulate
- complex systems, including expansion microscopy, robotic patch clamping, and even shrinking objects to the nanoscale.
- He was elected this year to the ranks of the National Academy of Sciences, and selected as
- an HHMI Investigator.
- Boyden has received numerous awards for this work, including the
- 2018 Gairdner International Prize and the
- 2016 Breakthrough Prize in Life Sciences.
SOURCE
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