Engineering Gene Circuits for Mammalian Cell–Based Applications

Ausländer, Simon; Fussenegger, Martin

doi:10.1101/cshperspect.a023895

Cited by 42 publications

(28 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The spectral compatibility of the NIR chromophore of BphP1 with blue-light-sensing domains and the small size of Q-PAS1 make them a pair of choice for multiplexing with other optogenetic tools and for engineering of multicomponent optogenetic assemblies. These multifunctional optogenetic systems will enable an advanced control of cell metabolism and gene regulation in synthetic biology and biomedical research 42,43 .…”

Section: Discussionmentioning

confidence: 99%

Near-infrared optogenetic pair for protein regulation and spectral multiplexing

et al. 2017

View full text Add to dashboard Cite

Multifunctional optogenetic systems are in high demand for use in basic and biomedical research. Near-infrared-light-inducible binding of bacterial phytochrome BphP1 to its natural PpsR2 partner is beneficial for simultaneous use with blue-light-activatable tools. However, applications of the BphP1–PpsR2 pair are limited by the large size, multidomain structure and oligomeric behavior of PpsR2. Here, we engineered a single-domain BphP1 binding partner, Q-PAS1, which is three-fold smaller and lacks oligomerization. We exploited a helix–PAS fold of Q-PAS1 to develop several near-infrared-light-controllable transcription regulation systems, enabling either 40-fold activation or inhibition. The light-induced BphP1–Q-PAS1 interaction allowed modification of the chromatin epigenetic state. Multiplexing the BphP1–Q-PAS1 pair with a blue-light-activatable LOV-domain-based system demonstrated their negligible spectral crosstalk. By integrating the Q-PAS1 and LOV domains in a single optogenetic tool, we achieved tridirectional protein targeting, independently controlled by near-infrared and blue light, thus demonstrating the superiority of Q-PAS1 for spectral multiplexing and engineering of multicomponent systems.

show abstract

Section: Discussionmentioning

confidence: 99%

Near-infrared optogenetic pair for protein regulation and spectral multiplexing

et al. 2017

View full text Add to dashboard Cite

show abstract

“…We can generate in this way synthetic networks that are either completely orthogonal to endogenous signaling or that rewire it. This concept, and the interchangeability of protein domains, underlies all the techniques at the heart of the synthetic biology tools for cellular signaling engineering [47,48]. More recently, this same approach has been used to build synthetic receptors, exploiting in this case the modularity present in both the extracellular/sensing domains and the intracellular/transduction domains of native receptors [49].…”

Section: Synthetic Biology Toolkit For Synthetic Tissue Developmentmentioning

confidence: 99%

Engineering multicellular systems: Using synthetic biology to control tissue self-organization

Johnson

March

Morsut

2017

Current Opinion in Biomedical Engineering

View full text Add to dashboard Cite

“…This controls the production of pre-messenger RNA (mRNA) transcripts that undergo post-transcriptional modifications including splicing introns out of the transcript and adding a 5’ cap and a 3’ poly (A) tail. These mature mRNAs are exported into the cytoplasm where they bind to ribosomes and undergo translation [67, 68]. The control of all of these processes is essential for cells to control gene expression to maintain their viability and to execute cell fate decisions.…”

Section: Introductionmentioning

confidence: 99%

Bottom-up approaches in synthetic biology and biomaterials for tissue engineering applications

Weisenberger

Deans

2018

Journal of Industrial Microbiology and Biotechnology

View full text Add to dashboard Cite

Synthetic biologists use engineering principles to design and construct genetic circuits for programming cells with novel functions. A bottom-up approach is commonly used to design and construct genetic circuits by piecing together functional modules that are capable of reprogramming cells with novel behavior. While genetic circuits control cell operations through the tight regulation of gene expression, a diverse array of environmental factors within the extracellular space also has a significant impact on cell behavior. This extracellular space offers an addition route for synthetic biologists to apply their engineering principles to program cell-responsive modules within the extracellular space using biomaterials. In this review, we discuss how taking a bottom-up approach to build genetic circuits using DNA modules can be applied to biomaterials for controlling cell behavior from the extracellular milieu. We suggest that, by collectively controlling intrinsic and extrinsic signals in synthetic biology and biomaterials, tissue engineering outcomes can be improved.

show abstract

Engineering Gene Circuits for Mammalian Cell–Based Applications

Cited by 42 publications

References 96 publications

Near-infrared optogenetic pair for protein regulation and spectral multiplexing

Near-infrared optogenetic pair for protein regulation and spectral multiplexing

Engineering multicellular systems: Using synthetic biology to control tissue self-organization

Bottom-up approaches in synthetic biology and biomaterials for tissue engineering applications

Contact Info

Product

Resources

About