Jared E. Toettcher
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View article: Depth-enhanced molecular imaging with two-photon oblique plane microscopy.
Depth-enhanced molecular imaging with two-photon oblique plane microscopy. Open
High-numerical-aperture (NA) oblique plane microscopy enables noninvasive fluorescence imaging of subcellular dynamics without requiring radical sample modification. However, performance degrades at depth in multicellular specimens as scat…
View article: PyCLM: programming-free, closed-loop microscopy for real-time measurement, segmentation, and optogenetic stimulation
PyCLM: programming-free, closed-loop microscopy for real-time measurement, segmentation, and optogenetic stimulation Open
In cell biology, optical techniques are increasingly used to measure cells’ internal states (biosensors) and to stimulate cellular responses (optogenetics). Yet the design of all-optical experiments is often manual: a pre-determined stimul…
View article: Multimodal control of Cas13 activity through domain insertion at an allosteric hotspot
Multimodal control of Cas13 activity through domain insertion at an allosteric hotspot Open
CRISPR-Cas13 RNA nucleases have emerged as powerful tools for programmable RNA targeting. A light-controlled RNA nuclease could be transformative by enabling researchers to selectively knock down transcripts at desired positions in a cell …
View article: Design and optimization of a kinase-controlled allosteric switch
Design and optimization of a kinase-controlled allosteric switch Open
Post-translational control enables rapid and precise regulation of cell behavior. Despite these advantages, general strategies to build phosphorylation-based synthetic circuits are limited. Here, we reasoned that engineered allostery, a te…
View article: <i>In vivo</i> measurements of receptor tyrosine kinase activity reveal feedback regulation of a developmental gradient
<i>In vivo</i> measurements of receptor tyrosine kinase activity reveal feedback regulation of a developmental gradient Open
A lack of tools for detecting receptor activity in vivo has limited our ability to fully explore receptor-level control of developmental patterning. Here, we extend a new class of biosensors for receptor tyrosine kinase (RTK) activity, the…
View article: CD44 and Ezrin restrict EGF receptor mobility to generate a novel spatial arrangement of cytoskeletal signaling modules driving bleb-based migration
CD44 and Ezrin restrict EGF receptor mobility to generate a novel spatial arrangement of cytoskeletal signaling modules driving bleb-based migration Open
Cells under high confinement form highly polarized hydrostatic pressure-driven, stable leader blebs that enable efficient migration in low adhesion, environments. Here we investigated the basis of the polarized bleb morphology of metastati…
View article: Engineered chimeric receptors for dissecting interferon signaling
Engineered chimeric receptors for dissecting interferon signaling Open
Though interferons (IFNs) were once heralded as panaceas to numerous diseases, how cells decode varying IFN stimuli and subsequently produce (in)appropriate signaling remain unclear. Our labs recently engineered novel erythropoietin recept…
View article: Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag
Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag Open
Biomolecular condensates are broadly implicated in both normal cellular regulation and disease. Consequently, several chemical biology and optogenetic approaches have been developed to induce phase separation of a protein of interest. Howe…
View article: Efficient Genome Editing with Chimeric Oligonucleotide-Directed Editing
Efficient Genome Editing with Chimeric Oligonucleotide-Directed Editing Open
Prime editing has emerged as a precise and powerful genome editing tool, offering a favorable gene editing profile compared to other Cas9-based approaches. Here we report new nCas9-DNA polymerase fusion proteins to create chimeric oligonuc…
View article: Large-scale control over collective cell migration using light-controlled epidermal growth factor receptors
Large-scale control over collective cell migration using light-controlled epidermal growth factor receptors Open
Receptor tyrosine kinases (RTKs) are thought to play key roles in coordinating cell movement at single-cell and tissue scales. The recent development of optogenetic tools for controlling RTKs and their downstream signaling pathways suggest…
View article: Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag
Rapid and reversible dissolution of biomolecular condensates using light-controlled recruitment of a solubility tag Open
Biomolecular condensates are broadly implicated in both normal cellular regulation and disease. Consequently, several chemical biology and optogenetic approaches have been developed to induce phase separation of a protein of interest. Howe…
View article: Membrane-proximal motifs encode differences in signaling strength between type I and III interferon receptors
Membrane-proximal motifs encode differences in signaling strength between type I and III interferon receptors Open
Interferons (IFNs) play crucial roles in antiviral defenses. Despite using the same Janus-activated kinase (JAK)–signal transducer and activator of transcription (STAT) signaling cascade, type I and III IFN receptors differ in the magnitud…
View article: Synthetic Heterodimers of Type III Interferon Receptors Require TYK2 for STAT Activation
Synthetic Heterodimers of Type III Interferon Receptors Require TYK2 for STAT Activation Open
Type III interferons (IFN-λ) are central to host defense against viral infection of epithelial barrier surfaces. IFN-λ binding to its receptor induces a JAK-STAT cascade through kinases Janus-associated kinase 1 (JAK1) and tyrosine kinase …
View article: Dynamics of an incoherent feedforward loop drive ERK-dependent pattern formation in the early <i>Drosophila</i> embryo
Dynamics of an incoherent feedforward loop drive ERK-dependent pattern formation in the early <i>Drosophila</i> embryo Open
Positional information in development often manifests as stripes of gene expression, but how stripes form remains incompletely understood. Here, we use optogenetics and live-cell biosensors to investigate the posterior brachyenteron (byn) …
View article: Control of gastruloid patterning and morphogenesis by the Erk and Akt signaling pathways
Control of gastruloid patterning and morphogenesis by the Erk and Akt signaling pathways Open
Many developmental processes rely on the localized activation of receptor tyrosine kinases and their canonical downstream effectors Erk and Akt, yet the specific roles played by each of these signals is still poorly understood. Gastruloids…
View article: Recording morphogen signals reveals origins of gastruloid symmetry breaking
Recording morphogen signals reveals origins of gastruloid symmetry breaking Open
When cultured in three dimensional spheroids, mammalian stem cells can reproducibly self-organize a single anterior-posterior axis and sequentially differentiate into structures resembling the primitive streak and tailbud. Whereas the embr…
View article: Light-switchable transcription factors obtained by direct screening in mammalian cells
Light-switchable transcription factors obtained by direct screening in mammalian cells Open
Optogenetic tools can provide fine spatial and temporal control over many biological processes. Yet the development of new light-switchable protein variants remains challenging, and the field still lacks general approaches to engineering o…
View article: pYtags enable spatiotemporal measurements of receptor tyrosine kinase signaling in living cells
pYtags enable spatiotemporal measurements of receptor tyrosine kinase signaling in living cells Open
Receptor tyrosine kinases (RTKs) are major signaling hubs in metazoans, playing crucial roles in cell proliferation, migration, and differentiation. However, few tools are available to measure the activity of a specific RTK in individual l…
View article: Author response: pYtags enable spatiotemporal measurements of receptor tyrosine kinase signaling in living cells
Author response: pYtags enable spatiotemporal measurements of receptor tyrosine kinase signaling in living cells Open
Full text Figures and data Side by side Abstract Editor's evaluation Introduction Results Discussion Methods Appendix 1 Data availability References Decision letter Author response Article and author information Metrics Abstract Receptor t…
View article: Dynamics of an incoherent feedforward loop drive ERK-dependent pattern formation in the early<i>Drosophila</i>embryo
Dynamics of an incoherent feedforward loop drive ERK-dependent pattern formation in the early<i>Drosophila</i>embryo Open
Positional information in developing tissues often takes the form of stripes of gene expression that mark the boundaries of a particular cell type or morphogenetic process. How stripes form is still in many cases poorly understood. Here we…
View article: Control of gastruloid patterning and morphogenesis by the Erk and Akt signaling pathways
Control of gastruloid patterning and morphogenesis by the Erk and Akt signaling pathways Open
Fibroblast growth factor (FGF) dependent elongation along an anterior-posterior (A-P) axis is a conserved feature of vertebrate embryogenesis. A-P axis elongation can also be reproduced in 3D cell culture models termed gastruloids, enablin…
View article: pYtags enable spatiotemporal measurements of receptor tyrosine kinase signaling in living cells
pYtags enable spatiotemporal measurements of receptor tyrosine kinase signaling in living cells Open
Receptor tyrosine kinases (RTKs) are major signaling hubs in metazoans, playing crucial roles in cell proliferation, migration, and differentiation. However, few tools are available to measure the activity of a specific RTK in individual l…
View article: Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation
Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation Open
Developmental patterning networks are regulated by multiple inputs and feedback connections that rapidly reshape gene expression, limiting the information that can be gained solely from slow genetic perturbations. Here we show that fast op…
View article: Stress ball morphogenesis: How the lizard builds its lung
Stress ball morphogenesis: How the lizard builds its lung Open
This study reveals how pressure drives the morphogenesis of cellular sheets into complex 3D architectures.
View article: Substratum stiffness regulates Erk signaling dynamics through receptor-level control
Substratum stiffness regulates Erk signaling dynamics through receptor-level control Open
The EGFR/Erk pathway is triggered by extracellular ligand stimulation, leading to stimulus-dependent dynamics of pathway activity. Although mechanical properties of the microenvironment also affect Erk activity, their effects on Erk signal…