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The molecular mechanisms of smell

Grant number: 11/51604-8
Support Opportunities:Research Projects - Thematic Grants
Duration: February 01, 2012 - January 31, 2017
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Bettina Malnic
Grantee:Bettina Malnic
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Mammals are able to discriminate a vast number of odorants through their sense of smell. In the nasal cavity there are millions of olfactory sensory neurons, which are responsible for this task. Odorants activate odorant receptors that are present in the cilia of the olfactory sensory neurons. The odorant receptors (ORs) belong to the G protein coupled receptor super family (GPCRs) and constitute a large family containing approximately 1000 genes in mice. In this project we aim to analyze two different aspects of the molecular organization of olfaction: (1) Each olfactory sensory neuron expresses one single gene out of the ~ 1000 OR genes, while the remaining genes remain silenced. We aim to investigate the molecular mechanisms involved in the regulation of OR gene expression. We will investigate whether epigenetic processes such as OR gene promoter methylation or non coding RNAs are involved in this regulation. (2) During odorant signal transduction, odorant receptors couple to an olfactory specific G protein, denominated Golf. We have shown that Ric-8B acts as a GEF (GTP exchange factor) on Golf in vitro. We now aim to determine the role played by Ric-8B in vivo in olfaction. To do this, we plan to obtain a tissue (olfactory epithelium) specific knock out for Ric-8B, since we have shown that the Ric-8B gene knock out is embryonic lethal. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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Scientific publications
(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)
XAVIER, ANDRE MACHADO; LUDWIG, RAISSA GUIMARAES; NAGAI, MAIRA HARUME; DE ALMEIDA, TIAGO JONAS; WATANABE, HEBE MIZUNO; HIRATA, MARCIO YUKIO; ROSENSTOCK, TATIANA ROSADO; PAPES, FABIO; MALNIC, BETTINA; GLEZER, ISAIAS. CD36 is expressed in a defined subpopulation of neurons in the olfactory epithelium. SCIENTIFIC REPORTS, v. 6, . (11/51604-8, 07/53732-8)
NAGAI, MAIRA H.; MARIA ARMELIN-CORREA, LUCIA; MALNIC, BETTINA. Monogenic and Monoallelic Expression of Odorant Receptors. MOLECULAR PHARMACOLOGY, v. 90, n. 5, p. 633-639, . (11/51604-8)
GONZALEZ-KRISTELLER, DANIELA C.; DO NASCIMENTO, JOAO B. P.; GALANTE, PEDRO A. F.; MALNIC, BETTINA. Identification of agonists for a group of human odorant receptors. FRONTIERS IN PHARMACOLOGY, v. 6, . (11/51604-8)

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