Nichole M. Daringer

Synthetic Phosphorylation Networks with Fluorescence and Luminescence Expansion

Leah Davis, Evan Hutt, Matthias Recktenwald, Samarth Siddharth Patel et autres

Synthetic receptors have emerged as powerful tools for precisely modulating cellular function. However, existing synthetic receptor platforms rely mainly on transcription-mediated reporting processes that are incompatible with the rapid and real-time dynamics of cellular signaling events. To address this limitation, we present …

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Engineering synthetic phosphorylation signaling networks in human cells

Xiaoyu Yang, Jason W. Rocks, Kaiyi Jiang, Andrew J. Walters et autres

Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles were assembled from modular protein domain parts and wired together to create synthetic phosphorylation …

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Extracellular Peptide-Ligand Dimerization Actuator Receptor Design for Reversible and Spatially Dosed 3D Cell-Material Communication

Matthias Recktenwald, Ritankar Bhattacharya, Mohammed Mehdi Benmassaoud, James MacAulay et autres

High Resolution Image Download MS PowerPoint Slide Transmembrane receptors that endow mammalian cells with the ability to sense and respond to biomaterial-bound ligands will prove instrumental in bridging the fields of synthetic biology and biomaterials. Materials formed with thiol-norbornene chemistry are amenable …

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Engineering transcriptional regulation for cell-based therapies

Matthias Recktenwald, Evan Hutt, Leah Davis, James MacAulay et autres

A major aim in the field of synthetic biology is developing tools capable of responding to user-defined inputs by activating therapeutically relevant cellular functions. Gene transcription and regulation in response to external stimuli are some of the most powerful and versatile of …

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Engineering synthetic phosphorylation signaling networks in human cells

Xiaoyu Yang, Jason W. Rocks, Kaiyi Jiang, Andrew J. Walters et autres

Protein phosphorylation signaling networks play a central role in how cells sense and respond to their environment. Here, we describe the engineering of artificial phosphorylation networks in which "push-pull" motifs-reversible enzymatic phosphorylation cycles consisting of opposing kinase and phosphatase activities-are assembled from …

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Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy

Leah Davis, Matthias Recktenwald, Evan Hutt, Schuyler R. Fuller et autres

Inadequate oxygen supply, or hypoxia, is characteristic of the tumor microenvironment and correlates with poor prognosis and therapeutic resistance. Hypoxia leads to the activation of the hypoxia-inducible factor (HIF) signaling pathway and stabilization of the HIF-α subunit, driving tumor progression. The homologous …

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Nucleic acid detection with CRISPR-Cas13a/C2c2

Jonathan S. Gootenberg, Omar O. Abudayyeh, Jeong Wook Lee, Patrick Essletzbichler et autres

Rapid, inexpensive, and sensitive nucleic acid detection may aid point-of-care pathogen detection, genotyping, and disease monitoring. The RNA-guided, RNA-targeting clustered regularly interspaced short palindromic repeats (CRISPR) effector Cas13a (previously known as C2c2) exhibits a "collateral effect" of promiscuous ribonuclease activity upon target …

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Rewiring human cellular input–output using modular extracellular sensors

Kelly A. Schwarz, Nichole M. Daringer, Taylor B. Dolberg, Joshua N. Leonard

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Rapid, Low-Cost Detection of Zika Virus Using Programmable Biomolecular Components

Keith Pardee, Alexander A. Green, Melissa K. Takahashi, Dana Braff et autres

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Contributions of Unique Intracellular Domains to Switchlike Biosensing by Toll-like Receptor 4

Nichole M. Daringer, Kelly A. Schwarz, Joshua N. Leonard

Toll-like receptors (TLRs) mediate immune recognition of both microbial infections and tissue damage. Aberrant TLR signaling promotes disease; thus, understanding the regulation of TLR signaling is of medical relevance. Although downstream mediators of TLR signaling have been identified, the detailed mechanism by …

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Modular Extracellular Sensor Architecture for Engineering Mammalian Cell-based Devices

Nichole M. Daringer, Rachel M. Dudek, Kelly A. Schwarz, Joshua N. Leonard

Engineering mammalian cell-based devices that monitor and therapeutically modulate human physiology is a promising and emerging frontier in clinical synthetic biology. However, realizing this vision will require new technologies enabling engineered circuitry to sense and respond to physiologically relevant cues. No existing …

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Biology by Design: From Top to Bottom and Back

Brian R. Fritz, Laura E. Timmerman, Nichole M. Daringer, Joshua N. Leonard et autres

Synthetic biology is a nascent technical discipline that seeks to enable the design and construction of novel biological systems to meet pressing societal needs. However, engineering biology still requires much trial and error because we lack effective approaches for connecting basic "parts" …

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