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BIO SEMINAR:Development of a DNA Origami platform for cryo-EM studies..

Speaker:Tural Aksel

Title: Development of a DNA Origami platform for cryo-EM studies of small proteins and nucleic acids

Date/Time:March 27, 2023 16:40PM


Abstract:Correct reconstruction of macromolecular structure by cryo-electron microscopy (cryo-EM)  relies on accurate determination of the orientation of single-particle images. For small  (<100 kDa) proteins, obtaining particle images with sufficiently asymmetric features to correctly  guide alignment is challenging. Here, we apply DNA origami to construct molecular  goniometers—instruments that precisely orient objects—and use them to dock a DNA-binding  protein on a double-helix stage that has user-programmable tilt and rotation angles. We  construct goniometers with 14 different stage configurations to orient and visualize the protein  just above the cryo-EM grid surface. Each goniometer has a distinct barcode pattern that we  use during particle classification to assign angle priors to the bound protein. We use  goniometers to obtain a 6.5-Å structure of BurrH, an 82-kDa DNA-binding protein whose helical  pseudosymmetry prevents accurate image orientation using traditional cryo-EM. Our approach  should be adaptable to other DNA-binding proteins as well as RNA and small proteins fused to  DNA-binding domains. In this seminar, I will go through the challenges that were addressed in  the process of developing this technology.

Bio:Tural Aksel is a Staff Scientist at Encodia, Inc., where he does protein engineering for a NextGen proteomics technology. He received his B.S. in Biological Sciences and Bioengineering from  Sabanci University, Turkey in 2006. He received his Ph.D. in Biophysics from Johns Hopkins  University in 2012. His Ph.D. studies were focused on repeat protein engineering and protein  folding. He performed his postdoctoral work on the biomechanics of human cardiac myosin at  Stanford University between 2013 and 2015. He was at the University of California, San  Francisco as postdoctoral researcher and later as programmer between 2015 and 2020 to  develop a DNA origami platform for cryo-EM. In 2020, he joined Nautilus Biotechnology, Inc. as  the Lead Staff Scientist to develop DNA Origami reagents for a NextGen proteomics platform. In  March 2023, he left Nautilus Biotechnology, Inc. to join Encodia, Inc. In San Diego. His research  interests are centered around developing technologies using biomolecular design and scientific  software development.


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