Vapor detection and discrimination with a panel of odorant receptors

Kida, Hitoshi; Fukutani, Yosuke; Mainland, Joel D.; March, Claire A. de; Vihani, Aashutosh; Li, Yun R.; Chi, Qiuyi; Toyama, Akemi; Liu, Linda; Kameda, Masaharu; Yohda, Masafumi; Matsunami, Hiroaki

doi:10.1038/s41467-018-06806-w

Cited by 76 publications

(57 citation statements)

References 60 publications

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“…Several approaches to augment the performance of machine olfactory systems [14,15], and even direct use of biological recognition elements (e.g. proteins, peptides) [16][17][18][19][20] or cultured cells/neurons [21][22][23][24] as transducers have been proposed. While these advances are significant, challenges remain in generating a rich repertoire of chemical transducers and translating the proposed approaches into low-cost, minimal-maintenance field-deployable units.…”

Section: Introductionmentioning

confidence: 99%

Explosive sensing with insect-based biorobots

Saha

Mehta

Atlan

et al. 2020

Preprint

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Stand-off chemical sensing is an important capability with applications in several domains including homeland security. Engineered devices for this task, popularly referred to as electronic noses, have limited capacity compared to the broad-spectrum abilities of the biological olfactory system. Therefore, we propose a hybrid bio-electronic solution that directly takes advantage of the rich repertoire of olfactory sensors and sophisticated neural computational framework available in an insect olfactory system. We show that select subsets of neurons in the locust (Schistocerca americana) brain were activated upon exposure to various explosive chemical species (such as DNT and TNT). Responses from an ensemble of neurons provided a unique, multivariate fingerprint that allowed discrimination of explosive vapors from non-explosive chemical species and from each other. Notably, target chemical recognition could be achieved within a few hundred milliseconds of exposure. Finally, we developed a minimally-invasive surgical approach and mobile multi-unit electrophysiological recording system to tap into the neural signals in a locust brain and realize a biorobotic explosive sensing system. In sum, our study provides the first demonstration of how biological olfactory systems (sensors and computations) can be hijacked to develop a cyborg chemical sensing approach. SUMMARY: We demonstrate a bio-robotic chemical sensing approach where signals from an insect brain are directly utilized to detect and distinguish various explosive chemical vapors.

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Section: Introductionmentioning

confidence: 99%

Explosive sensing with insect-based biorobots

Saha

Mehta

Atlan

et al. 2020

Preprint

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“…Each odorant has a variety of chemical features, and it is well known that the mouse may show preference when detecting odors (25,26). Olfactory signals are initiated in the periphery and propagate to the central olfactory system.…”

Section: Discussionmentioning

confidence: 99%

Region Specific Amyloid-β Accumulation in Olfactory Sensory Neurons Influences Ecto-Ventral Olfactory Dysfunction in 5xFAD Mice

Son

Yoo

Kang

et al. 2020

Preprint

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Background: Hyposmia in Alzheimer’s disease (AD) is a typical early symptom according to numerous previous clinical studies. Although the causes of damage have been proposed in every olfactory system including olfactory epithelium, olfactory bulb and olfactory cortex, the main causes of AD- related hyposmia are largely unknown. Methods: We here focused on peripheral olfactory sensory neurons (OSNs) and delved deeper into the direct relationship between pathophysiological and behavioral results using odorants. We also histologically confirmed the pathological changes in three-month-old 5xFAD mouse models which recapitulates AD pathology. We introduced a numeric scale histologically to compare physiological phenomenon and local tissue lesions regardless of anatomical plane. Results: We observed the odorant group, which 5xFAD mouse could not detect, also neither did physiologically activate the OSNs that propagate to the ventral olfactory bulb. Interestingly, the amount of accumulated amyloid-β (Aβ) was high in the ecto-ventrally located OSNs that showed reduced responses to odorants. We also observed irreversible damage to the ecto-region of the olfactory epithelium by measuring impaired neuronal turnover ratio from the basal cells to the matured OSNs. Conclusions: Our results showed that partial and asymmetrical accumulation of Aβ coincided with physiologically and structurally damaged areas in the peripheral olfactory system, which evoked hyporeactivity to some odorants. Taken together, partial olfactory dysfunction closely-associated with peripheral OSN’s loss could be a leading cause of the AD-related hyposmia, a characteristic of early AD.

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“…1A) was applied to construct RF, RPART and SVM classifiers. The data for model training was generated by in vitro measurements of the basal activity of 183 mammalian ORs, 108 of which were recently published 11 (Fig. 3C).…”

Section: Prediction Of or Basal Activitymentioning

confidence: 99%

“…ORs are also expressed ectopically, some of which have emerged as potential drug targets 7-9 . To date, ~45% of the human ORs (hORs) and ~10% of the mouse ORs (mORs) have been deorphanized with sometimes only one but also with more odorants (Table S1) [10][11][12][13][14][15][16] . We…”

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confidence: 99%

Functions of olfactory receptors are decoded from their sequence

Cong

Ren

Pacalon

et al. 2020

Preprint

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G protein-coupled receptors (GPCRs) conserve common structural folds and activation mechanisms, yet their ligand spectra and functions are highly diversified. This work investigated how the functional variations in olfactory GPCRs (ORs)−the largest GPCR family−are encoded in the primary sequence. With the aid of site-directed mutagenesis and molecular simulations, we built machine learning models to predict OR-ligand pairs as well as basal activity of ORs. In vitro functional assay confirmed 20 new OR-odorant pairs, including 9 orphan ORs. Residues around the odorant-binding pocket dictate the odorant selectivity/specificity of the ORs. Residues that encode the varied basal activities of the ORs were found to mostly surround the conserved motifs as well as the binding pocket. The machine learning approach, which is readily applicable to mammalian OR families, will accelerate OR-odorant mapping and the decoding of combinatorial OR codes for odors. IntroductionFunctions of proteins are encoded within either diversified or conserved subparts of their sequence. G protein-coupled receptors (GPCRs) are the most remarkable examples of this phenomenon. GPCRs are the largest membrane protein family and the targets of about 40% of marketed drugs 1 . The human genome contains over 800 genes coding for GPCRs, which exert differentiated and specific functions in the complex cellular signaling network. Half of these genes are olfactory receptors (ORs), which endow us with fascinating capacities of odor discrimination 2,3 . Mammalian GPCRs conserve a typical structural architecture of seven transmembrane helices (7TM) that house an orthosteric ligand-binding pocket 4 . Their intrinsic signaling mechanism, large-scale conformational changes to accommodate their cognate G proteins, is encoded in conserved motifs throughout the 7TM, which form a network of inter-TM contacts converging to their cytoplasmic part 5 . Namely, the "D(E)RY", "CWLP" and "NPxxY" motifs in TM3, TM6 and TM7, respectively, are the most conserved hubs of the allosteric communication between the orthosteric pocket and the cytoplasmic side of class A GPCRs 4 . The rest of the GPCR sequences, especially the ligand-binding pocket, have diversified extensively, which resulted in huge variations in the receptors' function. Amongst the hundreds of variable residues in the GPCR sequences, it is very likely that some are specialized for the receptors' ligand specificity/selectivity while, others encode more information on the receptors' intrinsic activity.This study focused on the divergence of ligand-dependent and ligand-independent (or basal) activities of olfactory class A GPCRs. We seek to identify amino acid positions that are critical for the receptors' functional heterogeneity. ORs discriminate a vast spectrum of volatile molecules (odorants) and code for an innumerous number of odors perceived in the brain. The manyto-many relationships between ORs and odorants are key to understanding odor perception 6 . ORs are also expressed ectopically, some of which have ...

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Vapor detection and discrimination with a panel of odorant receptors

Cited by 76 publications

References 60 publications

Explosive sensing with insect-based biorobots

Explosive sensing with insect-based biorobots

Region Specific Amyloid-β Accumulation in Olfactory Sensory Neurons Influences Ecto-Ventral Olfactory Dysfunction in 5xFAD Mice

Functions of olfactory receptors are decoded from their sequence

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