Harry M. Williams
@harrywilliams.bsky.social
Structural biologist currently working on microsecond time-resolved cryo-EM | Currently based in Lausanne at EPFL 🇨🇭
At 107 µs after photoactivation, we observe the K2 state. As we show, the chromophore has switched from the all-trans configuration present in the dark state to the 13-cis configuration. A switch that is accompanied by sidechain movements around the chromophore in the ErNaR active center.
November 22, 2025 at 11:26 AM
At 107 µs after photoactivation, we observe the K2 state. As we show, the chromophore has switched from the all-trans configuration present in the dark state to the 13-cis configuration. A switch that is accompanied by sidechain movements around the chromophore in the ErNaR active center.
Next, to demonstrate that we could conduct time-resolved cryo-EM experiments, we turned to the bacterial rhodopsin ErNaR. Normally, ErNaR pumps sodium ions from the cytoplasm across the bacterial membrane to the ouside. Using our setup, we wanted to probe some of the earlier photocycle states.
November 22, 2025 at 11:26 AM
Next, to demonstrate that we could conduct time-resolved cryo-EM experiments, we turned to the bacterial rhodopsin ErNaR. Normally, ErNaR pumps sodium ions from the cytoplasm across the bacterial membrane to the ouside. Using our setup, we wanted to probe some of the earlier photocycle states.
You can see these "timing lasers" and the "time of arrival laser" (or as I prefer to call it, the bouncy laser) working together here! In this video, the jet would normally come from the right hand side whereas the activation laser would be fired from the left hand side.
November 22, 2025 at 11:26 AM
You can see these "timing lasers" and the "time of arrival laser" (or as I prefer to call it, the bouncy laser) working together here! In this video, the jet would normally come from the right hand side whereas the activation laser would be fired from the left hand side.
We also took high-speed video frames of a similar jet and you can see these in the figure here. Now, a big part of our experiments is time. We want to accurately and precisely arrest protein dynamics at given timepoints to observe biological phenomena. To do this, we use a combination of lasers.
November 22, 2025 at 11:26 AM
We also took high-speed video frames of a similar jet and you can see these in the figure here. Now, a big part of our experiments is time. We want to accurately and precisely arrest protein dynamics at given timepoints to observe biological phenomena. To do this, we use a combination of lasers.
Here you can see the the cryogen jet traveling towards the grid, ultimately striking the grid and, in doing so, arresting protein dynamics.
November 22, 2025 at 11:26 AM
Here you can see the the cryogen jet traveling towards the grid, ultimately striking the grid and, in doing so, arresting protein dynamics.
Experimental concept: protein dynamics are initiated with a short laser pulse. As they unfold, the sample is vitrified with a time-delayed jet of a liquid cryogen, trapping the proteins in their transient configurations.
November 22, 2025 at 11:26 AM
Experimental concept: protein dynamics are initiated with a short laser pulse. As they unfold, the sample is vitrified with a time-delayed jet of a liquid cryogen, trapping the proteins in their transient configurations.
Always a good feeling!
November 19, 2025 at 5:41 PM
Always a good feeling!
The EPFL/UNIL sheep appear to be thoroughly enjoying the slow move into autumn.
October 7, 2025 at 3:06 PM
The EPFL/UNIL sheep appear to be thoroughly enjoying the slow move into autumn.
Finally, we looked at perhaps the most notorious sample known for preferred orientation: viral hemagglutinin. Even here, we demonstrate that ultrasonic excitation can be used to obtain a high-resolution isotropic 3D reconstruction. Comparing the orientation plots here reveals the key difference...
September 18, 2025 at 8:04 AM
Finally, we looked at perhaps the most notorious sample known for preferred orientation: viral hemagglutinin. Even here, we demonstrate that ultrasonic excitation can be used to obtain a high-resolution isotropic 3D reconstruction. Comparing the orientation plots here reveals the key difference...
We also looked at human CRP and similar to the 50S ribosomal subunit, with ultrasonic excitation we observe a broadening of the angular distribution and an improved 3D reconstruction. In this case, the 3D reconstruction derived from our ultrasonically excited sample pushes beyond 4 Å.
September 18, 2025 at 8:04 AM
We also looked at human CRP and similar to the 50S ribosomal subunit, with ultrasonic excitation we observe a broadening of the angular distribution and an improved 3D reconstruction. In this case, the 3D reconstruction derived from our ultrasonically excited sample pushes beyond 4 Å.
For the 50S ribosomal subunit, the use of ultrasonic excitation led to a broadening of the angular distribution (with new maxima appearing) and, ultimately, an improved 3D reconstruction with fewer of the streaky artefacts typically associated with directional anisotropy were reduced.
September 18, 2025 at 8:04 AM
For the 50S ribosomal subunit, the use of ultrasonic excitation led to a broadening of the angular distribution (with new maxima appearing) and, ultimately, an improved 3D reconstruction with fewer of the streaky artefacts typically associated with directional anisotropy were reduced.
Concept: we prepare samples by jetting while continuously exciting mechanical oscillations of the specimen support with an ultrasonic transducer. The motions induced in the thin liquid film continuously detach particles from the AWI, reshuffling their orientations improving the angular distribution.
September 18, 2025 at 8:04 AM
Concept: we prepare samples by jetting while continuously exciting mechanical oscillations of the specimen support with an ultrasonic transducer. The motions induced in the thin liquid film continuously detach particles from the AWI, reshuffling their orientations improving the angular distribution.
You cannot beat a Saturday afternoon plane spotting at Geneva. The smell of Jet A-1 really clears the mind.
September 6, 2025 at 6:22 PM
You cannot beat a Saturday afternoon plane spotting at Geneva. The smell of Jet A-1 really clears the mind.
Ciao Hamburg, you’ve been sweet. Next stop (eventually) Schweiz!
April 12, 2025 at 7:01 AM
Ciao Hamburg, you’ve been sweet. Next stop (eventually) Schweiz!
Finally managed to swing by hamburgpotter after 4 years for some adorable bits of pottery.
April 3, 2025 at 1:03 PM
Finally managed to swing by hamburgpotter after 4 years for some adorable bits of pottery.
As Nelly Furtado says, all good things come to an end and after ~4 years in Hamburg, it's time to move on! In the next week or so, I'll being moving ~1000 km south'ish to Switzerland to work on microsecond time-resolved single particle cryo-EM. Exciting times ahead!
April 2, 2025 at 4:20 PM
As Nelly Furtado says, all good things come to an end and after ~4 years in Hamburg, it's time to move on! In the next week or so, I'll being moving ~1000 km south'ish to Switzerland to work on microsecond time-resolved single particle cryo-EM. Exciting times ahead!
When doesn’t one’s brain need a hug?
March 29, 2025 at 3:03 PM
When doesn’t one’s brain need a hug?
Incredibly helpful FedEx, thank you so much. 👏
March 21, 2025 at 2:30 PM
Incredibly helpful FedEx, thank you so much. 👏
The sun has returned to Hamburg, and we love to see it.
March 19, 2025 at 3:49 PM
The sun has returned to Hamburg, and we love to see it.
A short trip to EPFL in Lausanne done, time to wind down for Christmas.
December 21, 2024 at 12:33 PM
A short trip to EPFL in Lausanne done, time to wind down for Christmas.
Saturdays at the Krios. 👌 May we proceed with thin ice, and nicely behaving particles.
November 23, 2024 at 12:01 PM
Saturdays at the Krios. 👌 May we proceed with thin ice, and nicely behaving particles.
🚨 Are PostDocs Alright? 🚨
Join us on 27.11.2024, for a joint event by the Leibniz PostDoc Network & German Postdoc Network as we discuss the latest findings from the Leibniz PostDoc survey!
🕛12:00-13:00 CET
Register now: bit.ly/40SQ6GA
#postdocs #IchBinHanna
Join us on 27.11.2024, for a joint event by the Leibniz PostDoc Network & German Postdoc Network as we discuss the latest findings from the Leibniz PostDoc survey!
🕛12:00-13:00 CET
Register now: bit.ly/40SQ6GA
#postdocs #IchBinHanna
November 22, 2024 at 4:57 PM
🚨 Are PostDocs Alright? 🚨
Join us on 27.11.2024, for a joint event by the Leibniz PostDoc Network & German Postdoc Network as we discuss the latest findings from the Leibniz PostDoc survey!
🕛12:00-13:00 CET
Register now: bit.ly/40SQ6GA
#postdocs #IchBinHanna
Join us on 27.11.2024, for a joint event by the Leibniz PostDoc Network & German Postdoc Network as we discuss the latest findings from the Leibniz PostDoc survey!
🕛12:00-13:00 CET
Register now: bit.ly/40SQ6GA
#postdocs #IchBinHanna
Though, I’m not sure how I feel seeing the same 24-well plates I used during my PhD as a museum exhibit. 😂
April 20, 2024 at 6:49 PM
Though, I’m not sure how I feel seeing the same 24-well plates I used during my PhD as a museum exhibit. 😂
Thoroughly enjoyed presenting our latest pre-print on the SFTSV L protein at the #GfV2024 meeting. Thanks again for the great opportunity @GesVirologie! In case you missed it, the pre-print is available here: www.biorxiv.org/content/10.1.... Paper soon to follow… I hope.
April 2, 2024 at 4:04 PM
Thoroughly enjoyed presenting our latest pre-print on the SFTSV L protein at the #GfV2024 meeting. Thanks again for the great opportunity @GesVirologie! In case you missed it, the pre-print is available here: www.biorxiv.org/content/10.1.... Paper soon to follow… I hope.