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Himes, Benjamin (2019) STRUCTURE DETERMINATION OF HETEROGENEOUS BIOLOGICAL SPECIMENS IN CROWDED ENVIRONMENTS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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The central dogma of molecular biology describes a strictly linear flow of genetic information stored in DNA transferred through RNA and translated into protein products. In the “post-genomic era” however, it is evident that abundant information flows from protein to protein and even protein back to DNA. The field of Structural Biology seeks to understand how the spatial and temporal organization of that information is stored and transmitted via the three-dimensional structure and dynamics of biological macromolecules. X-ray crystallography, nuclear magnetic resonance, and single particle cryo-electron microscopy (cryo-EM) are the primary techniques available to the structural biologist to deduce structure and dynamics at or near atomic resolutions. These tools are generally limited to the study of stable molecules that can be purified biochemically. Other approaches, like super-resolution light microscopy and cryo-electron tomography (cryo-ET), are amenable to the study of more labile macromolecular complexes or those found in situ; however, they are limited to resolutions of tens of nanometers. Improving the resolving capability of cryo-ET with sub-tomogram averaging to routinely reach beyond 10 Å is the primary goal of this work. My unique contribution to the field of structural biology is a suite of software tools called emClarity (enhanced macromolecular classification and alignment for high-resolution in situ tomography) which allows scientists with minimal computational background to probe the structural states of conformationally variable molecules present in complex and crowded environments.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Himes, Benjaminbah80@pitt.edubah800000-0001-7777-0298
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairConway,
Committee MemberFrank,
Committee MemberIshima,
Thesis AdvisorZhang,
Date: 3 January 2019
Date Type: Publication
Defense Date: 25 April 2018
Approval Date: 3 January 2019
Submission Date: 18 December 2018
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 132
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Molecular Biophysics and Structural Biology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: cryo-EM, sub-tomogram averaging, structural biology
Date Deposited: 03 Jan 2019 19:20
Last Modified: 03 Jan 2019 19:20


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