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Eric Betzig

@Eric_Betzig • 3,351 subscribers

An engineering physicist sometimes masquerading as a biologist or, on one occasion, a chemist. Aspiring astronaut. Nuclear is the way.

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True, even a two DOF system can exhibit chaotic behavior, and a single cell is an at least an ~10^7 DOF system (i.e., protein molecules per cell). I still fail to properly convey to others the insane complexity I see in our microscopes, and why successes like AlphaFold only work because of the huge number of unnatural constraints placed on the training data. Case in point (below): lysosome dynamics over 12 min across a 200 x 70 um region in the head of a developing zebrafish embryo, color-coded by depth -- just one of 20k proteins at work. Our Cell Observatory Initiative is more important than ever, but while we have petabytes of the most mind-blowing data ever, we are still hamstrung by insufficient AI talent and compute -- two resources in great demand everywhere. If anyone can help us over this hurdle, we'd be eternally grateful.

True, even a two DOF system can exhibit chaotic behavior, and a single cell is an at least an ~10^7 DOF system (i.e., protein molecules per cell). I still fail to properly convey to others the insane complexity I see in our microscopes, and why successes like AlphaFold only work because of the huge number of unnatural constraints placed on the training data. Case in point (below): lysosome dynamics over 12 min across a 200 x 70 um region in the head of a developing zebrafish embryo, color-coded by depth -- just one of 20k proteins at work. Our Cell Observatory Initiative is more important than ever, but while we have petabytes of the most mind-blowing data ever, we are still hamstrung by insufficient AI talent and compute -- two resources in great demand everywhere. If anyone can help us over this hurdle, we'd be eternally grateful.

29,632 views

Why not show real data instead of a 2D cartoon? Left diagonal: computationally separated 3D volume-rendered movies at 15 sec intervals for 19 minutes of chromosomes, mitochondria, and the ER in the same field of dividing pig kidney cells. Middle diagonal: overlapped color channels computationally sliced in slabs through the volume to reveal internal structure and interactions throughout mitosis. Upper right: zoomed in view in one slab, showing organelle rearrangements in the left cell from metaphase through telophase.

Why not show real data instead of a 2D cartoon? Left diagonal: computationally separated 3D volume-rendered movies at 15 sec intervals for 19 minutes of chromosomes, mitochondria, and the ER in the same field of dividing pig kidney cells. Middle diagonal: overlapped color channels computationally sliced in slabs through the volume to reveal internal structure and interactions throughout mitosis. Upper right: zoomed in view in one slab, showing organelle rearrangements in the left cell from metaphase through telophase.

19,923 views

MOSAIC lattice light sheet xy projection over 2+ hrs in human retinal pigment epithelial cells of endoplasmic reticulum remodeling (cyan) and transport of vesicles (yellow) containing β4-galactosyltransferase....

MOSAIC lattice light sheet xy projection over 2+ hrs in human retinal pigment epithelial cells of endoplasmic reticulum remodeling (cyan) and transport of vesicles (yellow) containing β4-galactosyltransferase....

28,943 views

MOSAIC large field of view 3D single molecule localization microscopy of mitochondrial outer membranes and nuclear membranes in fixed U2OS cells.

MOSAIC large field of view 3D single molecule localization microscopy of mitochondrial outer membranes and nuclear membranes in fixed U2OS cells.

27,218 views

#FluorescenceFriday #cellbiology 3D dynamics of six organelles in a COS-7 cell as revealed by lattice #lightsheet microscopy with multichannel unmixing. In collaboration with Valm Lab and Sarah Cohen, then in Lippincott-Schwartz Lab.

#FluorescenceFriday #cellbiology 3D dynamics of six organelles in a COS-7 cell as revealed by lattice #lightsheet microscopy with multichannel unmixing. In collaboration with Valm Lab and Sarah Cohen, then in Lippincott-Schwartz Lab.

25,320 views

#FluorescenceFriday #cellbiology #immunology #Actin dynamics at the immunological synapse (IS) between a Jurkat T cell and an antigen-presenting coverslip, as seen by total internal reflection structured illumination microscopy (TIRF-SIM). John Hammer's group #NIH used our TIRF-SIM to show that formins rearrange inward flowing actin filaments from the outer lamellipodial band of the IS into circumferential arcs that establish the peripheral supramolecular activation cluster, which in turn concentrates T cell receptor microclusters at the center of the IS.

#FluorescenceFriday #cellbiology #immunology #Actin dynamics at the immunological synapse (IS) between a Jurkat T cell and an antigen-presenting coverslip, as seen by total internal reflection structured illumination microscopy (TIRF-SIM). John Hammer's group #NIH used our TIRF-SIM to show that formins rearrange inward flowing actin filaments from the outer lamellipodial band of the IS into circumferential arcs that establish the peripheral supramolecular activation cluster, which in turn concentrates T cell receptor microclusters at the center of the IS.

26,283 views

#cellbiology #bioart The actin #cytoskeleton (green) is linked to a variety of transmembrane proteins through alpha-actinin (magenta), with such linkages being particularly dense in membrane ruffles and filopodia. As seen at 3 frames/min for 8 min by linear and non-linear structured illumination microscopy (97 and 60 nm resolution, respectively).

#cellbiology #bioart The actin #cytoskeleton (green) is linked to a variety of transmembrane proteins through alpha-actinin (magenta), with such linkages being particularly dense in membrane ruffles and filopodia. As seen at 3 frames/min for 8 min by linear and non-linear structured illumination microscopy (97 and 60 nm resolution, respectively).

25,403 views

#FluorescenceFriday #cellbiology #bioart The actin cytoskeleton at 60 nm resolution and 3 frames/min, and its association with early endosomes (Rab5a, green), as seen in a COS-7 cell by photoactivated nonlinear structured illumination microscopy

#FluorescenceFriday #cellbiology #bioart The actin cytoskeleton at 60 nm resolution and 3 frames/min, and its association with early endosomes (Rab5a, green), as seen in a COS-7 cell by photoactivated nonlinear structured illumination microscopy

25,842 views

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Early iSOAR 5D movie of membrane and mitochondria dynamics over 3 hrs at 3 min intervals in the head of a zebrafish embryo 6 dpf, covering a 300 x 1000 um FOV at 193 x 193 x 550 nm resolution (0.8 TB total).
0:59
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Early iSOAR 5D movie of membrane and mitochondria dynamics over 3 hrs at 3 min intervals in the head of a zebrafish embryo 6 dpf, covering a 300 x 1000 um FOV at 193 x 193 x 550 nm resolution (0.8 TB total).

Eric Betzig

19,689 views • 27 days ago

Relationship between chromosomes (orange) and the mitotic spindle (green) in four stages of cell division, as seen by Bessel Beam plane structured illumination microscopy
1:02
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Relationship between chromosomes (orange) and the mitotic spindle (green) in four stages of cell division, as seen by Bessel Beam plane structured illumination microscopy

Eric Betzig

64,768 views • 1 year ago

MOSAIC large field of view 3D single molecule localization microscopy of mitochondrial outer membranes and nuclear membranes in fixed U2OS cells.
0:20
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MOSAIC large field of view 3D single molecule localization microscopy of mitochondrial outer membranes and nuclear membranes in fixed U2OS cells.

Eric Betzig

27,218 views • 9 months ago

10/ With adaptive optical lattice light sheet microscopy (AO-LLSM), we’ve opened a stunningly beautiful and humblingly complex world of 4D subcellular processes viewed with high definition in living transparent multicellular organisms such as zebrafish.
1:04
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10/ With adaptive optical lattice light sheet microscopy (AO-LLSM), we’ve opened a stunningly beautiful and humblingly complex world of 4D subcellular processes viewed with high definition in living transparent multicellular organisms such as zebrafish.

Eric Betzig

46,182 views • 1 year ago

#FluorescenceFriday #cellbiology #bioart The interior of the cell is a busy place, as seen by grazing incidence structured illumination microscopy at 30 frames per minute: Lysosomes (green) can become corralled by the endoplasmic reticulum (ER, magenta), but can also remodel the ER when they are actively transported at high speed along microtubules (MTs, yellow). ER tubules are also remodeled directly when they associate with the growing or shrinking ends of MTs.
0:29
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#FluorescenceFriday #cellbiology #bioart The interior of the cell is a busy place, as seen by grazing incidence structured illumination microscopy at 30 frames per minute: Lysosomes (green) can become corralled by the endoplasmic reticulum (ER, magenta), but can also remodel the ER when they are actively transported at high speed along microtubules (MTs, yellow). ER tubules are also remodeled directly when they associate with the growing or shrinking ends of MTs.

Eric Betzig

41,974 views • 2 years ago

#FluorescenceFriday #cellbiology #bioart A neutrophilic cell migrating through a 3D collagen mesh at 1.3 sec intervals for 5.5 min, as seen by lattice light sheet microscopy.
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#FluorescenceFriday #cellbiology #bioart A neutrophilic cell migrating through a 3D collagen mesh at 1.3 sec intervals for 5.5 min, as seen by lattice light sheet microscopy.

Eric Betzig

37,597 views • 2 years ago

At #ASCB2024 today to speak in the session "Accelerating Discoveries in Cell Biology Using AI" about our Cell Observatory initiative to expand our understanding of subcellular physiology in the native multicellular environment by coupling advanced 4D imaging with AI. We're hiring, so if you're interested in an alternative to the traditional academic path and want to become part of a hard working interdisciplinary team taking on a crazy hard but potential transformative scientific challenge, join me in Room 30C at 3:15 PM.
0:38
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At #ASCB2024 today to speak in the session "Accelerating Discoveries in Cell Biology Using AI" about our Cell Observatory initiative to expand our understanding of subcellular physiology in the native multicellular environment by coupling advanced 4D imaging with AI. We're hiring, so if you're interested in an alternative to the traditional academic path and want to become part of a hard working interdisciplinary team taking on a crazy hard but potential transformative scientific challenge, join me in Room 30C at 3:15 PM.

Eric Betzig

25,551 views • 1 year ago

Aurora B kinase (green) distribution during initial cell divisions of a C elegans embryo relative to plasma membranes and nuclei (red), highlighting apical midbody remnants after cytokinesis. As seen by lattice light sheet microscopy. With Bembenek Lab
0:22
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Aurora B kinase (green) distribution during initial cell divisions of a C elegans embryo relative to plasma membranes and nuclei (red), highlighting apical midbody remnants after cytokinesis. As seen by lattice light sheet microscopy. With Bembenek Lab

Eric Betzig

24,310 views • 1 year ago

#FluorescenceFriday #zebrafish #bioart To see cells as they really are, it's necessary to see them in the native multicellular environment in which they evolved. However, the deeper we peer into living tissue, the more our view is obscured by optical aberrations. Here, take a trip as we dive 200 um down from the optic tectum to the hindbrain in a living zebrafish, turning on adaptive optics to correct these aberrations as we go, to see oligodendrocytes (orange) and neural nuclei (green).
0:51
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#FluorescenceFriday #zebrafish #bioart To see cells as they really are, it's necessary to see them in the native multicellular environment in which they evolved. However, the deeper we peer into living tissue, the more our view is obscured by optical aberrations. Here, take a trip as we dive 200 um down from the optic tectum to the hindbrain in a living zebrafish, turning on adaptive optics to correct these aberrations as we go, to see oligodendrocytes (orange) and neural nuclei (green).

Eric Betzig

26,318 views • 1 year ago

DAPI-stained nuclei in an L1-stage C. elegans larva, as seen by two-photon Bessel beam structured plane illumination microscopy.
0:41
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DAPI-stained nuclei in an L1-stage C. elegans larva, as seen by two-photon Bessel beam structured plane illumination microscopy.

Eric Betzig

20,177 views • 1 year ago

#FluorescenceFriday #cellbiology #bioart Three examples of mitochondrial remodeling by lysosomes/late endosomes actively transported along microtubules, as seen by grazing incidence structured illumination microscopy at 1-2 frames/sec.
0:29
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#FluorescenceFriday #cellbiology #bioart Three examples of mitochondrial remodeling by lysosomes/late endosomes actively transported along microtubules, as seen by grazing incidence structured illumination microscopy at 1-2 frames/sec.

Eric Betzig

23,079 views • 2 years ago

Correlative two color 3D super-resolution single molecule localization microscopy and block face electron microscopy of mitochondria and the endoplasmic reticulum in vitreously frozen COS-7 cells
2:44
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Correlative two color 3D super-resolution single molecule localization microscopy and block face electron microscopy of mitochondria and the endoplasmic reticulum in vitreously frozen COS-7 cells

Eric Betzig

16,036 views • 1 year ago

#FluorescenceFriday #neuroscience #bioart A minute sliver of some of the most complex matter in the known universe: a small subset of neurons (yellow) and pre- (blue) and post- (magenta) synaptic markers over 75 x 100 x 125 um in layers IV-V of the mouse primary somatosensory cortex, as seen by combined expansion and lattice light sheet microscopy (ExLLSM): The first six seconds show all pre/post synaptic pairs, the remainder shows only those pairs associated with the small subset of labeled dendritic spines. An insanely complicated computational machine.
0:36
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#FluorescenceFriday #neuroscience #bioart A minute sliver of some of the most complex matter in the known universe: a small subset of neurons (yellow) and pre- (blue) and post- (magenta) synaptic markers over 75 x 100 x 125 um in layers IV-V of the mouse primary somatosensory cortex, as seen by combined expansion and lattice light sheet microscopy (ExLLSM): The first six seconds show all pre/post synaptic pairs, the remainder shows only those pairs associated with the small subset of labeled dendritic spines. An insanely complicated computational machine.

Eric Betzig

17,465 views • 2 years ago

Dictyostelia are FAST. Microtubules in clustering Dicty cells, color coded by height above the substrate, at 2 sec intervals for 1430 time points (~48 min). As seen by lattice light sheet microscopy:
1:19
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Dictyostelia are FAST. Microtubules in clustering Dicty cells, color coded by height above the substrate, at 2 sec intervals for 1430 time points (~48 min). As seen by lattice light sheet microscopy:

Eric Betzig

15,114 views • 1 year ago

#FluorescenceFriday #cellbiology #microtubules 3/3 Growing MT tips tracked in 3D in relation to condensed chromosomes (orange) during different stages of mitosis, as seen by lattice light sheet microscopy
1:01
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#FluorescenceFriday #cellbiology #microtubules 3/3 Growing MT tips tracked in 3D in relation to condensed chromosomes (orange) during different stages of mitosis, as seen by lattice light sheet microscopy

Eric Betzig

15,227 views • 2 years ago

#FluorescenceFriday #Science #neuroscience Dendritic branches (green) in the mouse brain, studded with spines ("lollipops"), and myelin sheaths (pink tubes) that surround axons. Contacts between axons and dendrites called synapses facilitate communication between neurons. There are ~100 trillion synapses in the human brain, so collectively humanity has the same order of synapses as the 10^24 stars estimated in the observable universe. As seen by lattice light sheet expansion microscopy.
1:00
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#FluorescenceFriday #Science #neuroscience Dendritic branches (green) in the mouse brain, studded with spines ("lollipops"), and myelin sheaths (pink tubes) that surround axons. Contacts between axons and dendrites called synapses facilitate communication between neurons. There are ~100 trillion synapses in the human brain, so collectively humanity has the same order of synapses as the 10^24 stars estimated in the observable universe. As seen by lattice light sheet expansion microscopy.

Eric Betzig

16,355 views • 2 years ago

Actin filaments that drive amnioserosa cell shape changes during dorsal closure in Drosophila, (i.e., cytoskeletal contractions during fruit fly development) as seen by grazing incidence structured illumination microscopy:
0:20
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Actin filaments that drive amnioserosa cell shape changes during dorsal closure in Drosophila, (i.e., cytoskeletal contractions during fruit fly development) as seen by grazing incidence structured illumination microscopy:

Eric Betzig

15,909 views • 2 years ago

Organelle dynamics and sequential cell divisions for 200 time points at 44 sec intervals in the early zebrafish brain, 14 hours post fertilization. As seen by adaptive optical lattice light sheet microscopy:
1:30
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Organelle dynamics and sequential cell divisions for 200 time points at 44 sec intervals in the early zebrafish brain, 14 hours post fertilization. As seen by adaptive optical lattice light sheet microscopy:

Eric Betzig

11,944 views • 1 year ago

#FluorescenceFriday #neuroscience #neurodevelopment Axonal wiring of newly differentiated neurons stochastically labeled by Autobow in the spinal cord of a zebrafish embryo, 48-60 hours post fertilization, as seen by adaptive optical lattice light sheet microscopy
0:22
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#FluorescenceFriday #neuroscience #neurodevelopment Axonal wiring of newly differentiated neurons stochastically labeled by Autobow in the spinal cord of a zebrafish embryo, 48-60 hours post fertilization, as seen by adaptive optical lattice light sheet microscopy

Eric Betzig

13,075 views • 1 year ago

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