Speaker: Dr. Alberto Bartesaghi
Institution: Associate Professor of Computer Science, Biochemistry, Electrical and Computer Engineering At Duke University
Title: “Expanding the structural biologist’s toolbox with high-throughput cryo-electron microscopy.”
Host: Dr. Guozhou Xu

Abstract:
Improvements in detector technology and the introduction of novel data analysis techniques have transformed cryo-Electron Microscopy (EM) into a powerful strategy for structure determination that can be used to study a broad spectrum of biomedical targets. The resolutions achieved in some cases are high enough to reveal atomic level protein-compound interactions that are relevant for drug discovery. In particular, the ability to sort out structural heterogeneity combined with the capability of direct electron detectors to operate in movie mode, has provided unique opportunities for the development of effective algorithmic strategies capable of teasing out high-resolution information from noisy microscopy images. I will give an overview of the recent technical developments in the field that have allowed dramatic advances in automation and resolution, enabling the routine structural characterization of challenging targets including large dynamic assemblies, membrane transport proteins, and complexes bound to small molecules. I will also highlight some of the remaining technological barriers and challenges in computational image analysis that stand in the way of further advancing the frontiers of the field.

Short bio and research summary:

Alberto Bartesaghi received his B.Sc. and M.Sc. from the Department of Electrical Engineering at the Universidad de la Republica, Montevideo, Uruguay in 1999 and 2001 respectively, and his Ph.D. from the Department of Electrical and Computer Engineering at the University of Minnesota, Minneapolis, MN in 2005. He then joined the Biophysics Section of the Laboratory of Cell Biology at the NCI/NIH, Bethesda, MD to conduct his post-doctoral studies, and later became an Associate Scientist with the Center for Cancer Research. Dr. Bartesaghi received the “Norman P. Salzman Memorial Award in Virology” from the Foundation for the National Institutes of Health, Bethesda, MD for his work on the molecular architecture of native HIV-1 gp120 trimers. He recently joined the faculty in the Departments of Computer Science and Biochemistry at Duke University.

Research summary:

Dr. Bartesaghi is a pioneer in computational methods for solving structures of large macromolecular complexes by single particle cryo-EM, cryo-electron tomography and sub-volume averaging. His recently reported atomic resolution structure of an inhibitor-bound beta-galactosidase ranks among the highest resolution structures achieved to date by single particle cryo-EM. While at the NCI/NIH, Dr. Bartesaghi solved many influential structures including those of CRISPR/Cas9 complexes, GPCR/G-protein complexes, p97, and viral glycoproteins. He is also interested more broadly in machine learning, computer vision, brain imaging, image processing, and high-performance computing.