Breaking resolution barriers in cryo-EM: current state and computational challenges ahead

Speaker:Javier Vargas
Date: Wednesday, January 25, 2017
Time: 12:00pm - 1:00pm
Location: Holsti-Anderson Family Assembly Room, Perkins Library, Duke
Lunch will be served.

Abstract

X-ray crystallography has represented the dominant technique for obtaining high-resolution information of macromolecular complexes. Cryo-electron microscopy (cryo-EM) was traditionally used to shed light into the morphology of large protein complexes that resisted crystallization, albeit at substantially lower resolutions than crystallography. However, recent technological advances, mainly in computation and instrumentation levels, are now allowing cryo-EM to start being a competitive technique in terms of the level of details that can provide. Nevertheless, we should not rest on laurels as important challenges remains unsolved in cryo-EM and we need to encourage further progress to promote this technique to the next "omics" technology in structural biology. These challenges include among others: 1) development of high-thorughtput high-resolution computational methods, allowing in a close future the "one-push-one-map" philosophy; 2) implementation of new image processing methods to obtain high-resolution reconstructions using Volta phase plates with defocused samples; 3) new computational approaches to deal with both discrete and continuous heterogeneous samples; 4) development of robust 3D map validation methods. This seminar will introduce the computational improvements that have excited this field of cryo-EM, the computational challenges that are currently limiting its potential, and possible solutions to face them.

Biography

Javier Vargas received his B.Sc.in theoretical physics from the Universidad Complutense of Madrid in 2004 and Ph.D with Cum Laude distinction from the Optics Department of the same university in 2009. After postdoctoral research at the Space Optics Laboratory of the Spanish National Institute for Aerospace Technology, in 2011 became member of the Biocomputing Unit of the Spanish National Center for Biotechnology. In 2015 was awarded by a highly competitive ComFuturo grant, being at present PI of his own project titled "Advanced image processing in cryo-electron microscopy with impact in the pharmaceutical industry". In addition, he has enjoyed predoctoral and postdoctoral international stays at VISICS group in the KU Leuven (Belgium) and at the Leiden Medical Center (The Netherlands). Currently, he is lead guest editor for BioMed Research International Journal, member of the Biomedical Image & Signal Analytics team of the European Association for signal processing and associated scientist of the Instruct image processing center, which is the European reference center for image processing in structural biology. He is one of the main developers of Xmipp and Scipion electron microscopy software packages. His present work is focused on developing new computational methods in cryo-electron microscopy to obtain high-resolution reconstructions for current challenging macromolecular machines as small and/or highly heterogeneous samples.

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Contact: Marnie Rhoads