Eric Betzig

Physicist and neuroscientist based at the Janelia Research Campus. Awarded the 2014 Nobel Prize in Chemistry  for “the development of super-resolved fluorescence microscopy”.

Eric Betzig develops novel optical imaging tools in an effort to open new windows into molecular, cellular, and neurobiology. Betzig is focusing on improvements in five areas: Spatial Resolution, Temporal Resolution, Labeling Technology, Deep-Tissue Imaging, and Noninvasive, Data-Rich Imaging.

 

Eric Betzig

Eric BetzigPhysicist and neuroscientist based at the Janelia Research Campus. Awarded the 2014 Nobel Prize in Chemistry  for “the development of super-resolved fluorescence microscopy”.

Web Information

Janelia website:  janelia.org/people/scientist/eric-betzig
Betzig Lab:  www.janelia.org/lab/betzig-lab
Janelia Research Campus: neuroscience.onair.cc/2015/02/19/janelia-farm/

Contact Information

E-mail: betzige@janelia.hhmi.org
Phone:  (571) 209-4143
Work address: Janelia Research Campus, HHMI 19700 Helix Dr., 2C.185 Ashburn, VA 20147

Biography

Betzig was born in Ann Arbor, Michigan, the son of Robert and Helen Betzig. For his undergraduate degree, Betzig studiedPhysics at the California Institute of Technology, graduating with a BS degree in 1983. He then went on to study at Cornell University where he obtained an MS degree and a PhD degree in Applied and Engineering physics in 1985 and 1988, respectively.

After receiving his doctorate, Betzig worked at AT&T Bell Laboratories in the Semiconductor Physics Research Department. In 1996, Betzig left academia to become vice president of research and development at Ann Arbor Machine Company, then owned by his father and stepmother, Susan. Here he developed Flexible Adaptive Servohydraulic Technology (FAST) but did not achieve commercial success.

Betzig then returned to the field of microscopy, developing photoactivated localization microscopy (PALM) in the living room of his old Bell Labs collaborator, Harald Hess; and in 2006 he joined the Howard Hughes Medical Institute’s Janelia Farm Research Campus as a group leader to work on developing super high-resolution fluorescence microscopy techniques.

Betzig was awarded the William L. McMillan Award in 1992 and the 1993 National Academy of Sciences Award for Initiatives in Research. He was offered the 2010 Max Delbruck Prize, but declined. In 2014, Betzig was jointly awarded the Nobel Prize in Chemistry with Stefan Helland William E. Moerner. From Wikipedia 2/20/15  

For more biographical information, articles and news, and select research papers , see HHMI website

For Eric Betzig’s CV, see this PDF

Eric Betzig

Eric Betzig enjoys helping biologists answer challenging questions. Photograph by Stephen Voss. HHMI

Research

Pushing the Envelope in Biological Imaging

Due to its comparatively benign effect on living systems, optical microscopy has been the workhorse for dynamic studies of structure and function at the cellular level and below for more than 100 years. However, many questions at the forefront of molecular, cellular, and neurobiology remain beyond its current capabilities. At Janelia, I hope to collaborate with scientists and engineers across disciplines to extend these capabilities, to do so in ways that can be readily adopted by biologists, and to apply these methods in the service of my Janelia colleagues. From HHMI website “Our Scientists”

Imaging Life at High Spatiotemporal Resolution

In this lecture, held on 3/9/15 at UC Berkeley, Nobel Laureate Eric Betzig, describes three areas focused on addressing the challenges of high resolution imaging: super-resolution microscopy; plane illumination microscopy using non-diffracting beams; and adaptive optics to recover optimal images from within optically heterogeneous specimens.

At minute 10:30 to 12:30, Eric Betzig talks about how he likes to break new frontiers and his dissatisfaction with academia. Also from minute 1:13:00 repeats his goal is that his work is useful…that if these techniques are not able to answer biological questions, I will consider myself a failure… I have to get these tools into the hands of biologists. Have Advanced Imaging Center at Janelia that invites biologists to use their tools for one to two weeks…. want to disseminate the technology. “Prizes don’t matter, papers don’t matter… it’s the insights and accomplishments that matter.”

Betzig Lab

“We develop novel optical imaging tools in an effort to open new windows into molecular, cellular, and neurobiology.”

BETZIG LAB

Bioimaging technologies developed in our lab: superresolution photoactivated localization microscopy (PALM); pulse splitters for mediation of nonlinear photodamage; Bessel beam plane illumination for rapid three-dimensional live cell imaging; and adaptive optics for deep tissue imaging.

See Lab website for more information

 

Nobel Prize

OnAir logo 2014 Chemistry Nobel for Super-resolved fluorescence microscopy

“The Nobel Prize in Chemistry 2014 was awarded jointly to Eric Betzig, Stefan W. Hell and William E. Moerner “for the development of super-resolved fluorescence microscopy”.

For a long time optical microscopy was held back by a presumed limitation: that it would never obtain a better resolution than half the wavelength of light. Helped by fluorescent molecules the Nobel Laureates in Chemistry 2014 ingeniously circumvented this limitation. “Their ground-breaking work has brought optical microscopy into the nanodimension”, Nobel committee. From Neuroscience OnAir 2014 Chemistry Nobel overview, October 2014

2014 Chemistry Nobel for Super-resolved fluorescence microscopy

The Nobel Prize in Chemistry 2014 was awarded jointly to Eric Betzig, Stefan W. Hell and William E. Moerner”. Credits left to right: Photo- Matt Stanley/HHMI, (c) Bernd Schuller, Max Planck-Institut, Phto: K. Lowder via Wikimedia Commons, CC-BY SA 3.0

Chemistry Nobel Given To Scientists For Work On Optical Microscope

This year’s Nobel Prize in chemistry goes to three scientists who have revolutionized the optical microscope. Working independently, they’ve figured out how to expand the frontiers of biology by allowing researchers to see far more clearly into living cells. And this isn’t just a story of technology, but also of remarkable personalities.

After this triumph, Betzig wanted to get back into a lab so he could further develop this microscope and others like it. One thing led to another and he was offered a job at a posh new laboratory being built by the Howard Hughes Medical Institute, the Janelia Research Campus outside of Washington. Betzig took the job and has been there ever since. Hess eventually got a lab there, too.   NPR 10/8/14

Telephone Interview by Nobel

Telephone interview with Eric Betzig following the announcement of the 2014 Nobel Prize in Chemistry, 8 October 2014. The interviewer is Adam Smith, Chief Scientific Officer of Nobel Media. Hear about how he reacted with ”equal measures of happiness and fear” when he got the call from Stockholm. Transcription of interview can be read in link.

NobeEric Betzig was in Germany preparing for a keynote when he got the news that he had been awarded the 2014 Nobel Prize in Chemistry together with Stefan W. Hell and William E. Moerner.  Uploaded by Nobel Prize 10/8/15

Developing Palm Microscopy

During their 20-year friendship, Betzig and Hess worked together and separately, in academia and industry, before eventually joining forces to develop the first super-high-resolution PALM microscope. They tell us the story of this journey and emphasize how their unusual and varied backgrounds provided the skills to complete the project. iBiology Magazine 1/8/11

Lattice light sheet microscopy

New Microscope Collects Dynamic Images of the Molecules that Animate Life

Summary

Lattice light sheet microscopy, a new imaging platform developed at Janelia, lets biologists see 3-D images of subcellular activity in real time.

Highlights

  • Powerful new microscopes have dramatically sharpened biologists’ focus on the molecules that animate life.
  • A new imaging platform designed at Janelia produces high-resolution images with little light damage to cells.
  • The lattice light sheet microscope is available for scientists to use through Janelia’s Advanced Imaging Center.

Over the last decade, powerful new microscopes have dramatically sharpened biologists’ focus on the molecules that animate and propel life. Now, a new imaging platform developed by Eric Betzig and colleagues at the Howard Hughes Medical Institute’s Janelia Research Campus offers another leap forward for light microscopy. The new technology collects high-resolution images rapidly and minimizes damage to cells, meaning it can image the three-dimensional activity of molecules, cells, and embryos in fine detail over longer periods than was previously possible.

Thirty teams of biologists have come to Janelia over the past year to find out what the lattice light sheet microscope can reveal about the systems they study. Chen, Legant, and Wang have worked with the researchers to optimize the technology for a variety of experiments. “This is not a single imaging technique,” Wang says. “It’s an imaging platform.”  Press Release from HHMI News 10/23/15

Lattice light sheet microscopy– YouTube video uploaded by Marlyand Science 10/24/14

Launch Article in Science magazine

Lattice light-sheet microscopy: Imaging molecules to embryos at high spatiotemporal resolution

by Bi-Chang ChenWesley R. LegantKai WangLin ShaoDaniel E. MilkieMichael W. DavidsonChris JanetopoulosXufeng S. WuJohn A. Hammer IIIZhe LiuBrian P. EnglishYuko Mimori-KiyosueDaniel P. RomeroAlex T. RitterJennifer Lippincott-SchwartzLillian Fritz-LaylinR. Dyche MullinsDiana M. MitchellJoshua N. BembenekAnne-Cecile ReymannRalph BöhmeStephan W. GrillJennifer T. WangGeraldine SeydouxU. Serdar TuluDaniel P. Kiehart, Eric Betzig

Introduction

In vivo imaging provides a window into the spatially complex, rapidly evolving physiology of the cell that structural imaging alone cannot. However, observing this physiology directly involves inevitable tradeoffs of spatial resolution, temporal resolution, and phototoxicity. This is especially true when imaging in three dimensions, which is essential to obtain a complete picture of many dynamic subcellular processes. Although traditional in vivo imaging tools, such as widefield and confocal microscopy, and newer ones, such as light-sheet microscopy, can image in three dimensions, they sacrifice substantial spatiotemporal resolution to do so and, even then, can often be used for only very limited durations before altering the physiological state of the specimen.

Lattice light-sheet microscopy

Lattice light-sheet microscopy. An ultrathin structured light sheet (blue-green, center) excites fluorescence (orange) in successive planes as it sweeps through a specimen (gray) to generate a 3D image. The speed, noninvasiveness, and high spatial resolution of this approach make it a promising tool for in vivo 3D imaging of fast dynamic processes in cells and embryos, as shown here in five surrounding examples. Lattice light-sheet microscopy. An ultrathin structured light sheet (blue-green, center) excites fluorescence (orange) in successive planes as it sweeps through a specimen (gray) to generate a 3D image. The speed, noninvasiveness, and high spatial resolution of this approach make it a promising tool for in vivo 3D imaging of fast dynamic processes in cells and embryos, as shown here in five surrounding examples.

Rationale

To address these limitations, we developed a new microscope using ultrathin light sheets derived from two-dimensional (2D) optical lattices. These are scanned plane-by-plane through the specimen to generate a 3D image. The thinness of the sheet leads to high axial resolution and negligible photobleaching and background outside of the focal plane, while its simultaneous illumination of the entire field of view permits imaging at hundreds of planes per second even at extremely low peak excitation intensities. By implementing either superresolution structured illumination or by dithering the lattice to create a uniform light sheet, we imaged cells and small embryos in three dimensions, often at subsecond intervals, for hundreds to thousands of time points at the diffraction limit and beyond.

Results

We demonstrated the technique on 20 different biological processes spanning four orders of magnitude in space and time, including the binding kinetics of single Sox2 transcription factor molecules, 3D superresolution photoactivated localization microscopy of nuclear lamins, dynamic organelle rearrangements and 3D tracking of microtubule plus ends during mitosis, neutrophil motility in a collagen mesh, and subcellular protein localization and dynamics during embryogenesis in Caenorhabditis elegans and Drosophila melanogaster. Throughout, we established the performance advantages of lattice light-sheet microscopy compared with previous techniques and highlighted phenomena that, when seen at increased spatiotemporal detail, may hint at previously unknown biological mechanisms.

Conclusion

Photobleaching and phototoxicity are typically reduced by one to two orders of magnitude relative to that seen with a 1D scanned Bessel beam or the point array scanned excitation of spinning disk confocal microscopy. This suggests that the instantaneous peak power delivered to the specimen may be an even more important metric of cell health than the total photon dose and should enable extended 3D observation of endogenous levels of even sparsely expressed proteins produced by genome editing. Improvements of similar magnitude in imaging speed and a twofold gain in axial resolution relative to confocal microscopy yield 4D spatiotemporal resolution high enough to follow fast, nanoscale dynamic processes that would otherwise be obscured by poor resolution along one or more axes of spacetime. Last, the negligible background makes lattice light-sheet microscopy a promising platform for the extension of all methods of superresolution to larger and more densely fluorescent specimens and enables the study of signaling, transport, and stochastic self-assembly in complex environments with single-molecule sensitivity.  Science 10/24/15

Washington Post article

Weeks after winning a Nobel Prize for his microscope, Eric Betzig just revolutionized microscopy again

“Again, I just started to understand the limits of the technology,” Betzig said. PALM was great at looking at living systems, but only when they moved slowly. It couldn’t take  measurements quickly enough to get high-resolution pictures of fast cellular divisions.

But Betzig already has hopes of moving past the groundbreaking new tech. Lattice light sheet microscopy is advanced, but it still has its limits: Like all light-based microscopes, it can only take clear images of the surface of an object.”The eventual goal is to marry all of my work together to make a high-speed, high-resolution, low-impact tool that can look deep inside biological systems,” Betzig said. Washington Post 10/23/15 by Rachel Feltman

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