Chemi-Optogenetics: Photoactivatable Probes To Control Protein Proximity And Cellular Processes

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dc.contributor.advisorDavid M. Chenoweth
dc.contributor.advisorErnest J. Petersson
dc.contributor.authorWu, Daniel
dc.date2023-05-18T03:19:46.000
dc.date.accessioned2023-05-22T18:19:23Z
dc.date.available2024-01-05T00:00:00Z
dc.date.copyright2022-09-17T20:20:00-07:00
dc.date.issued2020-01-01
dc.date.submitted2022-09-17T12:48:02-07:00
dc.description.abstractChemi-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.
dc.description.degreeDoctor of Philosophy (PhD)
dc.format.extent310 p.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/31654
dc.languageen
dc.legacy.articleid6438
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=6438&context=edissertations&unstamped=1
dc.provenanceReceived from ProQuest
dc.rightsDaniel Wu
dc.source.issue4652
dc.source.journalPublicly Accessible Penn Dissertations
dc.source.statuspublished
dc.subject.otherChemical Biology
dc.subject.otherChemioptogenetics
dc.subject.otherDimerization
dc.subject.otherOptogenetics
dc.subject.otherPhotoactivation
dc.subject.otherPhotocages
dc.subject.otherCell Biology
dc.subject.otherChemistry
dc.subject.otherOrganic Chemistry
dc.titleChemi-Optogenetics: Photoactivatable Probes To Control Protein Proximity And Cellular Processes
dc.typeDissertation/Thesis
digcom.contributor.authorWu, Daniel
digcom.date.embargo2024-01-05T00:00:00-08:00
digcom.identifieredissertations/4652
digcom.identifier.contextkey31348553
digcom.identifier.submissionpathedissertations/4652
digcom.typedissertation
dspace.entity.typePublication
upenn.graduate.groupChemistry
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