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Odorant receptors: mechanisms of gene expression and signal transduction

Abstract

Odorants activate odorant receptors (ORs) that are present in the cilia of the olfactory sensory neurons. Odorant receptors are G protein coupled receptors (GPCRs) and belong to a large family composed of approximately 1000 genes in the mouse, and 400 genes in humans. In this project, we aim to analyze two different aspects related to the function of these receptors: (1) Each olfactory sensory neuron expresses one allele of a single gene out of the ~ 1000 OR genes (the so called 'one neuron one receptor rule'). Olfactory neurons show a singular nuclear architecture, which seems to be required for odorant receptor gene regulation. We plan to analyze the role played by specific histone marks (such as H3K27me3) and non-coding RNAs in the spatial organization of the odorant receptor genes in the nucleus. (2) During odorant signal transduction, odorant receptors couple to an olfactory specific Galpha protein, denominated Galphaolf. We have shown that Ric-8B acts as a GEF (GTP exchange factor) on Galphaolf in vitro. Analysis of knockout mice showed that the Ric-8B gene is essential for embryogenesis, and that knockout embryos show reduced mTOR function. We plan to investigate the molecular mechanisms involved in the regulation of mTOR function by Ric-8B. We have also produced a tissue (olfactory epithelium) specific knockout for Ric-8B. Recent experiments have shown that olfactory sensory neurons from these mice do not express the Galphaolf protein, and die more frequently. We plan now to examine the molecular mechanisms that lead to such a phenotype. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
Investigarán de qué manera el nuevo coronavirus afecta al olfato 
Project to investigate how the novel coronavirus affects the olfactory system 
Articles published in other media outlets (5 total):
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Palabras Claras (México): Investigarán de qué manera el nuevo coronavirus afecta al olfato (03/Jun/2020)
NCYT Amazings (Espanha): Investigarán de qué manera el nuevo coronavirus afecta al olfato (02/Jun/2020)
Noticias RevolucionWeb (Peru): Investigarán de qué manera el nuevo coronavirus afecta al olfato (02/Jun/2020)
Jornal da USP online: Projeto vai investigar como o novo coronavírus afeta o olfato (29/Apr/2020)
Algomais online: Projeto vai investigar como o novo coronavírus afeta o olfato (27/Apr/2020)

Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SBRANA, MARIANA FERREIRA; FORNAZIERI, MARCO AURELIO; BRUNI-CARDOSO, ALEXANDRE; AVELINO-SILVA, I, VIVIAN; SCHECHTMAN, DEBORAH; VOEGELS, RICHARD LOUIS; MALNIC, BETTINA; GLEZER, ISAIAS; PINNA, FABIO DE REZENDE. Olfactory Dysfunction in Frontline Health Care Professionals During COVID-19 Pandemic in Brazil. FRONTIERS IN PHYSIOLOGY, v. 12, MAR 9 2021. Web of Science Citations: 0.
LEME SILVA, ARTUR GUAZZELLI; NAGAI, MAIRA HARUME; NAKAHARA, THIAGO SEIKE; MALNIC, BETTINA. Genetic Background Effects on the Expression of an Odorant Receptor Gene. FRONTIERS IN CELLULAR NEUROSCIENCE, v. 15, FEB 25 2021. Web of Science Citations: 0.
NAGAI, MAIRA H.; XAVIER, VICTOR P. S.; GUTIYAMA, LUCIANA M.; MACHADO, CLEITON F.; REIS, ALICE H.; DONNARD, ELISA R.; GALANTE, PEDRO A. F.; ABREU, JOSE G.; FESTUCCIA, WILLIAM T.; MALNIC, BETTINA. Depletion of Ric-8B leads to reduced mTORC2 activity. PLOS GENETICS, v. 16, n. 5 MAY 2020. Web of Science Citations: 0.
CAMARGO, ANTONIO P.; NAKAHARA, THIAGO S.; FIRMINO, LUIZ E. R.; NETTO, PAULO H. M.; DO NASCIMENTO, JOAO B. P.; DONNARD, ELISA R.; GALANTE, PEDRO A. F.; CARAZZOLLE, MARCELO F.; MALNIC, BETTINA; PAPES, FABIO. Uncovering the mouse olfactory long non-coding transcriptome with a novel machine-learning model. DNA Research, v. 26, n. 4, p. 365-378, AUG 2019. Web of Science Citations: 0.
MACHADO, CLEITON F.; REIS-SILVA, THIAGO M.; LYRA, CASSANDRA S.; FELICIO, LUCIANO F.; MALNIC, BETTINA. Buried Food-seeking Test for the Assessment of Olfactory Detection in Mice. BIO-PROTOCOL, v. 8, n. 12 JUN 20 2018. Web of Science Citations: 1.
CRISAFULLI, UMBERTO; XAVIER, ANDRE M.; DOS SANTOS, FABIANA B.; CAMBIAGHI, TAVANE D.; CHANG, SEO Y.; PORCIONATTO, MARIMELIA; CASTILHO, BEATRIZ A.; MALNIC, BETTINA; GLEZER, ISAIAS. Topical Dexamethasone Administration Impairs Protein Synthesis and Neuronal Regeneration in the Olfactory Epithelium. FRONTIERS IN MOLECULAR NEUROSCIENCE, v. 11, MAR 6 2018. Web of Science Citations: 2.
MACHADO, CLEITON F.; NAGAI, MARIA H.; LYRA, CASSANDRA S.; REIS-SILVA, THIAGO M.; MACHADO, ANDRE M.; GLEZER, ISAIAS; FELICIO, LUCIANO F.; MALNIC, BETTINA. Conditional Deletion of Ric-8b in Olfactory Sensory Neurons Leads to Olfactory Impairment. JOURNAL OF NEUROSCIENCE, v. 37, n. 50, p. 12202-12213, DEC 13 2017. Web of Science Citations: 3.

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