The molecular mechanisms of smell

• Grant number: 11/51604-8
• Support Opportunities: Research Projects - Thematic Grants
• Start date: February 01, 2012
• End date: 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
• City of the host institution: São Paulo

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)

Scientific publications

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

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, MAY 5 2016. (11/51604-8, 07/53732-8)

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, MAR 3 2015. (11/51604-8)

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, NOV 1 2016. (11/51604-8)