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Organizers: Joakim Andén, Dorit Hanein, Roy R. Lederman and Steven J. Ludtke
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Next Talk
Amit Moscovich
Assistant Professor, Department of Statistics and Operations Research, Tel Aviv University
Date and time: May 3rd, 2023
Wednesday, at 8am PDT / 11am EDT / 4pm BST/ 5pm CEST / 11pm China
For the zoom and gather.town links, please join the One World Cryo-EM mailing list.
Tools for heterogeneity in cryo-EM: manifold learning, disentanglement and optimal transport
Despite much recent progress, the reconstruction and analysis of macromolecules with continuous conformational heterogeneity remains a key challenge. In this talk we present two promising tools that can aid in various stages of the reconstruction and analysis pipelines.
In the first part of the talk, the notion of manifold factorization and disentanglement is presented. This is an approach to dimensionality reduction where different aspects of the data are assigned separate coordinates. It has potential applications both for the reconstruction of single-particle cryo-EM samples with continuous heterogeneity and for the analysis of the reconstructed volumetric datasets.
In the second part of the talk, we will discuss the potential applications of optimal transport for cryo-EM, in particular for the analysis of heterogeneous samples, as well as for class-averaging and particle picking. Optimal transport metrics are closely related to physical motion, making them a natural choice for many of the core problems in cryo-EM. Historically, computational bottlenecks have limited the applicability of optimal transport. However, recent advances in computational optimal transport have yielded fast approximation schemes that can be readily used for the analysis of high-resolution images and volumetric arrays.
Last Talk
Petar Petrov
Postdoctoral Scholar at University of California, Berkeley
Date and time: March 1st, 2023
Wednesday, at 8am PST / 11am EST / 4pm GMT / 5pm CET / midnight China
For the zoom and gather.town links, please join the One World Cryo-EM mailing list.
Laser phase-contrast Cryo-EM and associated computational opportunities
A phase plate can provide optimum image contrast for weak-phase objects in transmission electron microscopy, but approaches toward realizing a phase plate have suffered from instabilities. We have developed a phase plate that is based on coherently phase-shifting the electron wave function by a laser beam, which is built up to a record-high intensity of ~400 GW/cm^2 by resonance in a Fabry-Perot cavity. We have demonstrated contrast enhancement with the laser phase plate (LPP) and shown the long-term stability of the device, as well as generated a high-resolution map of 20S proteasome particles using a standard single-particle cryo-electron microscopy (Cryo-EM) workflow.
This talk will focus on our recent work to move beyond proof-of-concept, as well as the computational opportunities that lie ahead. To demonstrate the benefits of the LPP to Cryo-EM as well as cryo-electron tomography, we will soon begin working with a state-of-the-art microscope equipped with a spherical aberration corrector, gun monochromator, and post column energy filter. We will explore improvements to the phase plate design and pursue new strategies for image acquisition and processing, such as high-resolution two-dimensional template matching.
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