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primary topic: Engineering optogenetic control of p53

Engineering optogenetic control of p53
type: Article
abstract: Cells respond to external and internal stimuli mostly with changes in transcription of target genes. Gene expres- sion is mediated by transcription factors, central nodes in highly regulated signalling networks. In multiple sig- nalling pathways, different stimuli converge on the same transcription factor, yet induce different cell fates. Re- cently, the dynamics of transcription factors have been identiﬁed to play a key role in converting the received trigger into the appropriate response. It is proposed that the same transcription factor induces different gene expression programs purely depending on its dynamics. One example of particular interest is the transcription factor p53. Under physiological conditions, p53 levels are kept low by a tightly regulated network. Upon stress, p53 levels increase and show a pulsatile or sustained behaviour, depending on the type and severityof the stress. Interestingly, it was proposedthat p53 dynamics dic- tate which downstream gene expression programs are initiated. However, many questions remain open, such as whether the dynamics are sufﬁcient to drive differential gene expression, or whether stress-induced post- translational modiﬁcations of p53 and other interacting factors play a role alongside p53 dynamics. Moreover, it is still unknown, how p53 dynamics are eventually translated into a speciﬁc target gene expression programs. The p53 signalling and regulatory network is both, highly complex and dynamic. Understanding this network requires targeted dissection using speciﬁc and precise methods. To address these requirements, I employed op- togenetic methods, as light possesses unmatched spatial and temporal resolution. In contrast to chemical per- turbation methods, light as a trigger is non-invasive and has a superior speciﬁcity. Here, I used optogenetics to reconstitute various p53 dynamics, by controlling the levels and localization of p53, and I investigated the out- come of these manipulations in the absence of upstre…
date: 2019
author list: authors
type: EPrint
type: DoctoralThesisEPrint
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Engineering optogenetic control of p53 (PDF)
type: Document
has file: PhD Thesis - Final Version.pdf
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Pierre Wehler
type: Person
given name: Pierre
family name: Wehler

Engineering optogenetic control of p53 (Other)
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Engineering optogenetic control of p53 (Other)
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primary topic: Engineering optogenetic control of p53