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Genetic Variation Across the Human Olfactory Receptor Repertoire Alters Odor Perception
bioRxiv preprint doi: https://doi.org/10.1101/212431; this version posted November 1, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Genetic variation across the human olfactory receptor repertoire alters odor perception Casey Trimmer1,*, Andreas Keller2, Nicolle R. Murphy1, Lindsey L. Snyder1, Jason R. Willer3, Maira Nagai4,5, Nicholas Katsanis3, Leslie B. Vosshall2,6,7, Hiroaki Matsunami4,8, and Joel D. Mainland1,9 1Monell Chemical Senses Center, Philadelphia, Pennsylvania, USA 2Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, New York, USA 3Center for Human Disease Modeling, Duke University Medical Center, Durham, North Carolina, USA 4Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, USA 5Department of Biochemistry, University of Sao Paulo, Sao Paulo, Brazil 6Howard Hughes Medical Institute, New York, New York, USA 7Kavli Neural Systems Institute, New York, New York, USA 8Department of Neurobiology and Duke Institute for Brain Sciences, Duke University Medical Center, Durham, North Carolina, USA 9Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA *[email protected] ABSTRACT The human olfactory receptor repertoire is characterized by an abundance of genetic variation that affects receptor response, but the perceptual effects of this variation are unclear. To address this issue, we sequenced the OR repertoire in 332 individuals and examined the relationship between genetic variation and 276 olfactory phenotypes, including the perceived intensity and pleasantness of 68 odorants at two concentrations, detection thresholds of three odorants, and general olfactory acuity. -
Database Tool the Systematic Annotation of the Three Main GPCR
Database, Vol. 2010, Article ID baq018, doi:10.1093/database/baq018 ............................................................................................................................................................................................................................................................................................. Database tool The systematic annotation of the three main Downloaded from https://academic.oup.com/database/article-abstract/doi/10.1093/database/baq018/406672 by guest on 15 January 2019 GPCR families in Reactome Bijay Jassal1, Steven Jupe1, Michael Caudy2, Ewan Birney1, Lincoln Stein2, Henning Hermjakob1 and Peter D’Eustachio3,* 1European Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK, 2Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada and 3New York University School of Medicine, New York, NY 10016, USA *Corresponding author: Tel: +212 263 5779; Fax: +212 263 8166; Email: [email protected] Submitted 14 April 2010; Revised 14 June 2010; Accepted 13 July 2010 ............................................................................................................................................................................................................................................................................................. Reactome is an open-source, freely available database of human biological pathways and processes. A major goal of our work is to provide an integrated view of cellular signalling processes that spans from ligand–receptor -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
A Mathematical Paradigm for Designing Full Length
Goswami et al. Genome Biology 2010, 11(Suppl 1):P15 http://genomebiology.com/2010/11/S1/P15 POSTER PRESENTATION Open Access L-Systems: a mathematical paradigm for designing full length human genes and genomes Arunava Goswami1*, Pabitra Pal Choudhury2, Amita Pal3, R L Brahmachary1, Sk Sarif Hassan2 From Beyond the Genome: The true gene count, human evolution and disease genomics Boston, MA, USA. 11-13 October 2010 We have shown how L-Systems can generate both an the whole mitochondrial genome (exons and introns) exon (human OR) and a system containing both exons generated by the L-Systems. and introns (human mitochondria). Ligands for only two human olfactory (OR) receptors are known. One Author details of them, OR1D2, binds to Bourgeonal, a volatile che- 1Biological Sciences Division, Indian Statistical Institute, 203 B. T. Road, mical constituent of the fragrance Lily of the valley Calcutta, 700108, India. 2Applied Statistics Unit, Indian Statistical Institute, 203 3 (Convallaria majalis). OR1D2, OR1D4 and OR1D5 are B. T.Road, Calcutta, 700108, India. Bayesian Interdisciplinary Research Unit (BIRU), Indian Statistical Institute, 203 B. T. Road, Calcutta, 700108, India. three full- length olfactory receptors present in an olfactory locus in human genome. These receptors are Published: 11 October 2010 more than 80% identical in DNA sequences and have 108 base pair mismatches among them. We have used L-system mathematics to show a closely related sub- doi:10.1186/gb-2010-11-S1-P15 family of OR1D2, OR1D4 and OR1D5. Craig Venter’s Cite this article as: Goswami et al.: L-Systems: a mathematical paradigm for designing full length human genes and genomes. -
The Odorant Receptor OR2W3 on Airway Smooth Muscle Evokes Bronchodilation Via a Cooperative Chemosensory Tradeoff Between TMEM16A and CFTR
The odorant receptor OR2W3 on airway smooth muscle evokes bronchodilation via a cooperative chemosensory tradeoff between TMEM16A and CFTR Jessie Huanga,1,2, Hong Lama,1, Cynthia Koziol-Whiteb,c, Nathachit Limjunyawongd, Donghwa Kime, Nicholas Kimb, Nikhil Karmacharyac, Premraj Rajkumarf, Danielle Firera, Nicholas M. Dalesiog, Joseph Judec, Richard C. Kurtenh, Jennifer L. Pluznickf, Deepak A. Deshpandei, Raymond B. Penni, Stephen B. Liggette,j, Reynold A. Panettieri Jrc, Xinzhong Dongd,k, and Steven S. Anb,c,2 aDepartment of Environmental Health and Engineering, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205; bDepartment of Pharmacology, Rutgers-Robert Wood Johnson Medical School, The State University of New Jersey, Piscataway, NJ 08854; cRutgers Institute for Translational Medicine and Science, New Brunswick, NJ 08901; dSolomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; eCenter for Personalized Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612; fDepartment of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; gDepartment of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205; hDepartment of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205; iDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Center for Translational Medicine, Jane and Leonard Korman -
The Potential Druggability of Chemosensory G Protein-Coupled Receptors
International Journal of Molecular Sciences Review Beyond the Flavour: The Potential Druggability of Chemosensory G Protein-Coupled Receptors Antonella Di Pizio * , Maik Behrens and Dietmar Krautwurst Leibniz-Institute for Food Systems Biology at the Technical University of Munich, Freising, 85354, Germany; [email protected] (M.B.); [email protected] (D.K.) * Correspondence: [email protected]; Tel.: +49-8161-71-2904; Fax: +49-8161-71-2970 Received: 13 February 2019; Accepted: 12 March 2019; Published: 20 March 2019 Abstract: G protein-coupled receptors (GPCRs) belong to the largest class of drug targets. Approximately half of the members of the human GPCR superfamily are chemosensory receptors, including odorant receptors (ORs), trace amine-associated receptors (TAARs), bitter taste receptors (TAS2Rs), sweet and umami taste receptors (TAS1Rs). Interestingly, these chemosensory GPCRs (csGPCRs) are expressed in several tissues of the body where they are supposed to play a role in biological functions other than chemosensation. Despite their abundance and physiological/pathological relevance, the druggability of csGPCRs has been suggested but not fully characterized. Here, we aim to explore the potential of targeting csGPCRs to treat diseases by reviewing the current knowledge of csGPCRs expressed throughout the body and by analysing the chemical space and the drug-likeness of flavour molecules. Keywords: smell; taste; flavour molecules; drugs; chemosensory receptors; ecnomotopic expression 1. Introduction Thirty-five percent of approved drugs act by modulating G protein-coupled receptors (GPCRs) [1,2]. GPCRs, also named 7-transmembrane (7TM) receptors, based on their canonical structure, are the largest family of membrane receptors in the human genome. -
WO 2019/068007 Al Figure 2
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2019/068007 Al 04 April 2019 (04.04.2019) W 1P O PCT (51) International Patent Classification: (72) Inventors; and C12N 15/10 (2006.01) C07K 16/28 (2006.01) (71) Applicants: GROSS, Gideon [EVIL]; IE-1-5 Address C12N 5/10 (2006.0 1) C12Q 1/6809 (20 18.0 1) M.P. Korazim, 1292200 Moshav Almagor (IL). GIBSON, C07K 14/705 (2006.01) A61P 35/00 (2006.01) Will [US/US]; c/o ImmPACT-Bio Ltd., 2 Ilian Ramon St., C07K 14/725 (2006.01) P.O. Box 4044, 7403635 Ness Ziona (TL). DAHARY, Dvir [EilL]; c/o ImmPACT-Bio Ltd., 2 Ilian Ramon St., P.O. (21) International Application Number: Box 4044, 7403635 Ness Ziona (IL). BEIMAN, Merav PCT/US2018/053583 [EilL]; c/o ImmPACT-Bio Ltd., 2 Ilian Ramon St., P.O. (22) International Filing Date: Box 4044, 7403635 Ness Ziona (E.). 28 September 2018 (28.09.2018) (74) Agent: MACDOUGALL, Christina, A. et al; Morgan, (25) Filing Language: English Lewis & Bockius LLP, One Market, Spear Tower, SanFran- cisco, CA 94105 (US). (26) Publication Language: English (81) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of national protection available): AE, AG, AL, AM, 62/564,454 28 September 2017 (28.09.2017) US AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 62/649,429 28 March 2018 (28.03.2018) US CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, (71) Applicant: IMMP ACT-BIO LTD. -
Olfactory Receptors in Non-Chemosensory Tissues
BMB Reports Invited Mini Review Olfactory receptors in non-chemosensory tissues NaNa Kang & JaeHyung Koo* Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea Olfactory receptors (ORs) detect volatile chemicals that lead to freezing behavior (3-5). the initial perception of smell in the brain. The olfactory re- ORs are localized in the cilia of olfactory sensory neurons ceptor (OR) is the first protein that recognizes odorants in the (OSNs) in the olfactory epithelium (OE) and are activated by olfactory signal pathway and it is present in over 1,000 genes chemical cues, typically odorants at the molecular level, in mice. It is also the largest member of the G protein-coupled which lead to the perception of smell in the brain (6). receptors (GPCRs). Most ORs are extensively expressed in the Tremendous research was conducted since Buck and Axel iso- nasal olfactory epithelium where they perform the appropriate lated ORs as an OE-specific expression in 1991 (7). OR genes, physiological functions that fit their location. However, recent the largest family among the G protein-coupled receptors whole-genome sequencing shows that ORs have been found (GPCRs) (8), constitute more than 1,000 genes on the mouse outside of the olfactory system, suggesting that ORs may play chromosome (9, 10) and more than 450 genes in the human an important role in the ectopic expression of non-chemo- genome (11, 12). sensory tissues. The ectopic expressions of ORs and their phys- Odorant activation shows a distinct signal transduction iological functions have attracted more attention recently since pathway for odorant perception. -
Sean Raspet – Molecules
1. Commercial name: Fructaplex© IUPAC Name: 2-(3,3-dimethylcyclohexyl)-2,5,5-trimethyl-1,3-dioxane SMILES: CC1(C)CCCC(C1)C2(C)OCC(C)(C)CO2 Molecular weight: 240.39 g/mol Volume (cubic Angstroems): 258.88 Atoms number (non-hydrogen): 17 miLogP: 4.43 Structure: Biological Properties: Predicted Druglikenessi: GPCR ligand -0.23 Ion channel modulator -0.03 Kinase inhibitor -0.6 Nuclear receptor ligand 0.15 Protease inhibitor -0.28 Enzyme inhibitor 0.15 Commercial name: Fructaplex© IUPAC Name: 2-(3,3-dimethylcyclohexyl)-2,5,5-trimethyl-1,3-dioxane SMILES: CC1(C)CCCC(C1)C2(C)OCC(C)(C)CO2 Predicted Olfactory Receptor Activityii: OR2L13 83.715% OR1G1 82.761% OR10J5 80.569% OR2W1 78.180% OR7A2 77.696% 2. Commercial name: Sylvoxime© IUPAC Name: N-[4-(1-ethoxyethenyl)-3,3,5,5tetramethylcyclohexylidene]hydroxylamine SMILES: CCOC(=C)C1C(C)(C)CC(CC1(C)C)=NO Molecular weight: 239.36 Volume (cubic Angstroems): 252.83 Atoms number (non-hydrogen): 17 miLogP: 4.33 Structure: Biological Properties: Predicted Druglikeness: GPCR ligand -0.6 Ion channel modulator -0.41 Kinase inhibitor -0.93 Nuclear receptor ligand -0.17 Protease inhibitor -0.39 Enzyme inhibitor 0.01 Commercial name: Sylvoxime© IUPAC Name: N-[4-(1-ethoxyethenyl)-3,3,5,5tetramethylcyclohexylidene]hydroxylamine SMILES: CCOC(=C)C1C(C)(C)CC(CC1(C)C)=NO Predicted Olfactory Receptor Activity: OR52D1 71.900% OR1G1 70.394% 0R52I2 70.392% OR52I1 70.390% OR2Y1 70.378% 3. Commercial name: Hyperflor© IUPAC Name: 2-benzyl-1,3-dioxan-5-one SMILES: O=C1COC(CC2=CC=CC=C2)OC1 Molecular weight: 192.21 g/mol Volume -
Functional and Structural Characterization of Olfactory Receptors in Human Heart and Eye
DISSERTATION to obtain the degree Doctor Rerum Naturalium (Dr.rer.nat.) at the Faculty of Biology and Biotechnology International Graduate School Biosciences Ruhr-University Bochum Functional and structural characterization of olfactory receptors in human heart and eye Department of Cellphysiology submitted by Nikolina Jovancevic from Zadar, Croatia Bochum February 2016 First Referee: Prof. Dr. Dr. Dr. Hanns Hatt Second Referee: Prof. Dr. Stefan Wiese DISSERTATION zur Erlangung des Grades eines Doktors der Naturwissenschaften der Fakultät für Biologie und Biotechnologie an der Internationalen Graduiertenschule Biowissenschaften der Ruhr-Universität Bochum Funktionale und strukturelle Charakterisierung olfaktorischer Rezeptoren im humanen Herzen und Auge Lehrstuhl für Zellphysiologie vorgelegt von Nikolina Jovancevic aus Zadar, Kroatien Bochum Februar 2016 Referent: Prof. Dr. Dr. Dr. Hanns Hatt Korreferent: Prof. Dr. Stefan Wiese To my family TABLE OF CONTENTS TABEL OF CONTENT 1 INTRODUCTION 1 1.1 G protein-coupled receptors 1 1.1.1 General 1 1.1.2 Structure and classification 2 1.1.3 Olfactory Receptors 4 1.2 Function of olfactory receptors 9 1.2.1 The olfactory system 9 1.2.2 Ectopic expression of olfactory receptors 11 1.3 Excursus: Anatomy and physiology of the heart 13 1.3.1 Anatomy of the heart and blood circuit 14 1.3.2 The cardiac conduction system 15 1.3.3 Excitation-contraction coupling 16 1.3.4 Cardiac GPCRs: Modulation of cardiac contraction 17 1.4 Excursus: Anatomy and physiology of the eye 18 1.4.1 Anatomy of the retina 19 -
Molecular Triggers of Symptoms of Parosmia and Insights Into the Underlying Mechanism
Molecular triggers of symptoms of parosmia and insights into the underlying mechanism Simon Gane ( [email protected] ) Royal National Ear, Nose and Throat and Eastman Dental Hospitals Jane Parker University of Reading https://orcid.org/0000-0003-4121-5481 Christine Kelly AbScent Article Keywords: coffee, COVID-19, GC-olfactometry, mis-wiring, olfactory disorder, parosmia Posted Date: June 29th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-583178/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/21 Abstract The molecular stimuli that trigger a parosmic response have been identied. Parosmia is a debilitating condition in which familiar smells become distorted and unpleasant, frequently leading to clinical depression. Often a result of post infectious smell loss, incidences are increasing as COVID-19 cases escalate worldwide. Until now, there was little understanding of its pathophysiology, and the prevailing hypothesis for the underlying mechanism is a mis-wiring of olfactory sensory neurons. However, with novel application of avour chemistry techniques as a relatively rapid screening tool for assessment of both quantitative and qualitative olfactory loss, we identied 15 different molecular triggers in coffee. This provides evidence for peripheral causation, but places constraints on the mis-wiring theory. Furthermore, it provides the basis for development of a practical diagnostic tool and treatment strategies. Introduction Prior to the COVID-19 pandemic, olfactory dysfunction was largely unrecognised, and often underestimated by health care professionals. Since the spread of SARS-CoV-2, and the realisation that 50-65% of cases result in anosmia (the loss of sense of smell)1, there is a greater awareness of the debilitating effect of olfactory disorders2. -
L-Systems: a Mathematical Paradigm for Designing Full Length Genes and Genomes GJCST Classification Sk
Global Journal of Computer Science and Technology Vol. 10 Issue 4 Ver. 1.0 June 2010 P a g e | 119 L-Systems: A Mathematical Paradigm For Designing Full Length Genes And Genomes GJCST Classification Sk. Sarif Hassana,c,1, Pabitra Pal Choudhurya, J.3, G.1.0, I.2.1 Amita Palb,R. L. Brahmacharyc and Arunava Goswamic,1 Abstract- We have shown how L-Systems can generate long kb). This was a phenomenal discovery. Gibson et al (2009) genomic sequences. This has been achieved in two steps. In the [2] in a paper published in Nature Methods showed long first, a single L-System turned out to be sufficient to construct DNA chain could made easily using an elegant experimental a full length human olfactory receptor gene. This however is method in which concerted action of a 5' exonuclease, a only an exon. The more complicated problem of generating a DNA polymerase and a DNA ligase lead to a genome containing both exon and intron, such as that of thermodynamically favored isothermal single reaction. In human mitochondrial genome has been now addressed. We have succeeded in establishing a set of L-Systems and thus the beginning, researchers recessed DNA fragments and this solved the problem. In this context we have discussed the process yielded single-stranded DNA overhangs that recent attempts at Craig Venter’s group to experimentally specifically annealed, and then covalently joined them. In construct long DNA molecules adopting a number of working this process, they could assemble multiple overlapping DNA hypotheses. A mathematical rule for generating such long molecules and surely enough mechanism of action behind sequences would shed light on various fundamental problems making a full chromosome is now ready.