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Chemi-optogenetics : photoactivatable probes to control protein proximity and cellular processes / Daniel Zeng Wu.

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Format:
Book
Thesis/Dissertation
Author/Creator:
Wu, Daniel Zeng, author.
Contributor:
Chenoweth, David M., degree supervisor.
Petersson, E. James, degree supervisor.
University of Pennsylvania. Department of Chemistry, degree granting institution.
Language:
English
Subjects (All):
Organic chemistry.
Cellular biology.
Chemistry.
Chemistry--Penn dissertations.
Penn dissertations--Chemistry.
Local Subjects:
Organic chemistry.
Cellular biology.
Chemistry.
Chemistry--Penn dissertations.
Penn dissertations--Chemistry.
Genre:
Academic theses.
Physical Description:
1 online resource (311 pages)
Contained In:
Dissertations Abstracts International 82-07B.
Place of Publication:
[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2020.
Language Note:
English
System Details:
Mode of access: World Wide Web.
text file
Summary:
Chemi-optogenetics is a hybrid chemical and genetic approach that utilizes light to regulate cellular processes. We combined the chemical versatility of photoremovable protecting groups with the biological specificity of self-labelling proteins (i.e. Halo-tag, SNAP-tag, eDHFR), to develop a series of tools that localize proteins of interest to its target with spatiotemporal precision. The local proximity of a protein and its substrate is sufficient to initiate a desired biological effect, as the probably of an effective collision is a function of proximity. Therefore, chemically induced proximity is a valuable technique for probing cellular processes. The removal of a photocage is irreversible and done with a single pulse of light, which enables us to study submicron targets that move quickly within three-dimensional space. This would be otherwise unfeasible with reversible systems such as photo-switches or optogenetic proteins that typically require constant illumination. However, biological processes are often reversible, therefore we developed reversible and bidirectional tools to probe these processes as well. We demonstrate reversible and bidirectional control of subcellular protein localization using sequential pulses of light and apply it to manipulate dynamic biological events. This work expands the boundaries of chemi-optogenetic control of biological processes and highlight the advantages of a genetic and chemical hybrid approach.
Notes:
Source: Dissertations Abstracts International, Volume: 82-07, Section: B.
Advisors: Chenoweth, David M.; Petersson, E. James; Committee members: Gary Molander; A. Rhoades.
Department: Chemistry.
Ph.D. University of Pennsylvania 2020.
Local Notes:
School code: 0175
ISBN:
9798557059299
Access Restriction:
Restricted for use by site license.
This item is not available from ProQuest Dissertations & Theses.
This item must not be sold to any third party vendors.

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