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Biology subjects

Shin, Y.-H.

Publications and source records attributed to Shin, Y.-H..

4 recordsLinked to original sources

An ancient receptor family illuminates the evolution of animal sensation

Animals use nervous systems to sense and respond to their environment. Yet single-celled organisms can also detect cues to execute diverse behaviors, suggesting that core components for animal sensation predate multicellularity and nervous systems. Here, we report that choanoflagellates, the closest living animal relatives, use an ancient sensory receptor family to detect bacterial prey. These receptors are related to transient receptor potential ion channels but are distinguished by WD40 domains, defining TRPW. TRPW1 detects specific bacterial lipids to modulate flagellar beating, providing a mechanism for attraction towards prey. TRPW emerged in early eukaryotes and reveals ancestral architectural and ligand-binding features that predate animal somatosensory receptors. In multicellular choanoflagellates, TRPW1 elicits collective responses, linking bacterial ecology to the evolution of receptors, sensory organelles, and multicellular life.

evolutionary biology↗

Aerocavin is an antibiotic with potent and specific anti-Neisserial activity

Gonorrhea, caused by N. gonorrhoeae, is a widespread sexually transmitted disease that is becoming resistant to all currently used antibiotics. Therefore, new therapeutics against gonorrhea are desperately needed. Here, we show that a natural product - aerocavin, is highly potent and specific against Neisseria. Aerocavin accumulates in N. gonorrhoeae at high levels and inhibits bacterial RNA polymerase (RNAP) by binding the switch region. Aerocavin resistance mutations evolve in N. gonorrhoeae at a low rate and are absent in clinical isolates. Previously overlooked narrow-spectrum antimicrobials like aerocavin may enable microbiome-sparing treatments of gonorrhea.

microbiology↗

Acetoacetate suppresses colon cancer via an MR1-MAIT axis

Colorectal cancer (CRC) is a leading cause of cancer mortality and additional preventative, and therapeutic strategies are urgently needed. Ketogenic diets have mixed effects on tumorigenesis and compliance is challenging. Exogenous ketones, {beta}-hydroxybutyrate ({beta}HB) or acetoacetate (AcAc), offer an alternative approach. While {beta}HB has been investigated, the anti-cancer effects of AcAc are poorly defined. Here, we show that orally administering ethyl AcAc (EAA) suppresses tumor growth in several pre-clinical CRC models. Single-cell RNA sequencing, flow cytometry, and genetic and antibody-mediated depletion studies reveal that EAA selectively expands and activates cytotoxic mucosal-associated invariant T (MAIT) cells in an MHC class I-related protein 1 (MR1)-dependent manner. EAA increases MR1 expression by tumor monocytes, which is recapitulated in human cell cultures, where AcAc and 5-amino-6-D-ribitylaminouracil (5-A-RU) induce MAIT cell expansion and tumor killing. Mechanistically, AcAc converts to methylglyoxal, combining with microbially-derived 5-A-RU to generate 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), a potent MR1 ligand. These findings identify an AcAc-MR1-MAIT cell axis as a potential immunotherapy approach for CRC therapy.

immunology↗

Environmental microbiomes drive chemotactile sensation in octopus

Microbial communities coat nearly every surface in the environment and have co-existed with animals throughout evolution. Whether animals exploit omnipresent microbial cues to navigate their surroundings is not well understood. Octopuses use "taste by touch" chemotactile receptors (CRs) to explore the seafloor, but how they distinguish meaningful surfaces from the rocks and crevices they encounter is unknown. Here, we report that secreted signals from microbiomes of ecologically relevant surfaces activate CRs to guide octopus behavior. Distinct molecules isolated from specific bacterial strains located on prey or eggs bind single CRs in subtly different structural conformations to elicit distinct mechanisms of receptor activation, ion permeation and signal transduction, and maternal care and predation behavior. Thus, microbiomes on ecological surfaces act at the level of primary sensory receptors to inform behavior. Our study demonstrates that uncovering interkingdom interactions is essential to understanding how animal sensory systems evolved in a microbe rich world. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/641191v1_ufig1.gif" ALT="Figure 1"> View larger version (140K): org.highwire.dtl.DTLVardef@15f365eorg.highwire.dtl.DTLVardef@1ea5606org.highwire.dtl.DTLVardef@1b5ad1aorg.highwire.dtl.DTLVardef@779e6e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIChemotactile receptors (CRs) detect microbiomes of prey and progeny C_LIO_LIDiverse microbial signals bind single CRs with distinct structural conformations C_LIO_LIDistinct microbial signals activate single CRs to permeate different ions C_LIO_LIEnvironmental microbes elicit octopus predatory and maternal behaviors C_LI

physiology↗