• Molecular Neuroscience
The mammalian olfactory system is capable of discriminating thousands of odorants. Odorants are detected by olfactory receptors (ORs) expressed in the olfactory neurons of the nose. These receptors belong to the G protein-coupled receptor (GPCR) superfamily and exhibit extremely diverse amino acid sequences, which is consistent with their ability to recognize a large number of odorants. Odorant discrimination derives from the different specificities of the ORs. Different odorants are recognized by different combinations of ORs, indicating that the OR family is used combinatorially to encode the identities of a large number of odorants. OR genes are dispersed throughout the genome, and each olfactory neuron in the nose expresses only one of these 1000 OR genes. We are exploring the molecular mechanisms involved in odorant signal transduction in olfactory neurons. We are also investigating the mechanisms responsible for the peculiar gene expression pattern of the genes that encode for the ORs.
• Selected publications
Malnic B, Hirono J, Sato T, Buck LB. Combinatorial receptor codes for odors. Cell. 1999 Mar 5;96(5):713-23. https://doi.org/10.1016/s0092-8674(00)80581-4
Godfrey PA, Malnic B, Buck LB. The mouse olfactory receptor gene family. PNAS. 2004 Feb 17;101(7):2156-61. https://doi.org/10.1073/pnas.0308051100
Malnic B, Godfrey PA, Buck LB. The human olfactory receptor gene family. PNAS 2004 Feb 24;101(8):2584-9. https://doi.org/10.1073/pnas.0307882100
Von Dannecker LE, Mercadante AF, Malnic B. Ric-8B, an olfactory putative GTP exchange factor, amplifies signal transduction through the olfactory-specific G-protein Galphaolf. J Neurosci. 2005 Apr 13;25(15):3793-800. https://doi.org/10.1523/jneurosci.4595-04.2005
Von Dannecker LE, Mercadante AF, Malnic B. Ric-8B promotes Functional expression of odorant receptors. PNAS. 2006 Jun 13;103(24):9310-4. https://doi.org/10.1073/pnas.0600697103
Michaloski JS, Galante PA, Malnic B. Identification of potential regulatory motifs in odorant receptor genes by analysis of promoter sequences. Genome Res. 2006 Sep;16(9):1091-8. https://doi.org/10.1101/gr.5185406
Machado CF, Nagai MH, Lyra CS, Reis-Silva TM, Xavier AM, Glezer I, Felicio LF, Malnic B. Conditional Deletion of Ric-8b in Olfactory Sensory Neurons Leads to Olfactory Impairment. J Neurosci. 2017 Dec 13;37(50):12202-12213. https://doi.org/10.1523/jneurosci.0943-17.2017
Armelin-Correa LM, Malnic B. Combining In Vivo and In Vitro Approaches To Identify Human Odorant Receptors Responsive to Food Odorants. J Agric Food Chem. 2018 Mar 14;66(10):2214-2218. https://doi.org/10.1021/acs.jafc.6b04998
Armelin-Correa LM, Malnic B. Capturing genome folds in single sensory neurons. Nat Struct Mol Biol. 2019 Apr;26(4):254-255. https://doi.org/10.1038/s41594-019-0212-3
Nagai MH, Xavier VPS, Gutiyama LM, Machado CF, Reis AH, Donnard ER, Galante PAF, Abreu JG, Festuccia WT, Malnic B. Depletion of Ric-8B leads to Reduced mTORC2 activity. PLoS Genet. 2020 May 11;16(5):e1008255. https://doi.org/10.1371/journal.pgen.1008255
Leme Silva AG, Nagai MH, Nakahara TS, Malnic B. Genetic Background Effects on the Expression of an Odorant Receptor Gene. Front Cell Neurosci. 2021 Feb 25;15:646413. https://doi.org/10.3389/fncel.2021.646413
Glezer I, Bruni-Cardoso A, Schechtman D, Malnic B. Viral infection and smell loss: The case of COVID-19. J Neurochem. 2021 May;157(4):930-943. https://doi.org/10.1111/jnc.15197
Ruiz Tejada Segura ML, Abou Moussa E, Garabello E, Nakahara TS, Makhlouf M, Mathew LS, Wang L, Valle F, Huang SSY, Mainland JD, Caselle M, Osella M, Lorenz S, Reisert J, Logan DW, Malnic B, Scialdone A, Saraiva LR. A 3D transcriptomics atlas of the mouse nose sheds light on the anatomical logic of smell. Cell Rep. 2022 Mar 22;38(12):110547. https://doi.org/10.1016/j.celrep.2022.110547
Naressi RG, Schechtman D, Malnic B. Odorant receptors as potential drug targets. Trends Pharmacol Sci. 2023 Jan;44(1):11-14. https://doi.org/10.1016/j.tips.2022.08.003
Naressi RG, Malnic B. Engineered receptors show how humans tell countless odour molecules apart. Nature. 2024 Nov;635(8038):295-296. https://doi.org/10.1038/d41586-024-03396-0
• Members
Bettina Malnic
Full Professor
e-mail: bmalnic@iq.usp.br
André Machado Xavier
Post-doctoral Fellow
e-mail: andremx@usp.br
Caio Martins de Castro
Post-doctoral Fellow
e-mail: caioukz@usp.br
Rafaella Gonçalves Naressi
Post-doctoral Fellow
e-mail: rafaellanaressi@usp.br
Victor P. De Sá Xavier
Ph.D Student
Isabella de Oliveira Escarminio
Undergraduate Student
e-mail: isabella.escarminio@usp.br
Erica Bandeira
Laboratory Technician
e-mail: ericamig@gmail.com
Daniella Sabino Battagello
Research Project Manager
e-mail: daniella@iq.usp.br
Érika Estella Dias dos Santos
Animal Facility Technician
e-mail: vet.erikaestella@gmail.com
• Alumni
Adriana F. Mercadante
Post-doctoral Fellow
Cleiton Fagundes Machado
Post-doctoral Fellow
Daniela Carvalho Gonzalez Kristeller
Post-doctoral Fellow
Lúcia Armelin-Correa
Post-doctoral Fellow
Maíra H. Nagai
Post-doctoral Fellow
Marcela Davalos
Post-doctoral Fellow
Geraldo Santana Magalhães
Post-doctoral Fellow
Artur Guazzelli Leme silva
Ph.D Student
Cassandra S. de Lyra
Ph.D Student
Daniel Shikanai Kerr
Ph.D Student
João Batista Plácido do Nascimento
Ph.D Student
Jussara S. Michaloski
Ph.D Student
Lílian Tiemi Inoue
Ph.D Student
Luciana Gutiyama
Ph.D Student
Luiz Eduardo Cabral Von Dannecker
Ph.D Student
Luiz Eduardo Rodrigues Firmino
Ph.D Student
Pedro A. F. Galante
Ph.D Student
Tiago Jonas de Almeida
Ph.D Student
Guilherme Louzada Silva Meira
Ph.D Student
Victor P. De Sá Xavier
MS Student
Ana Carolina Bottura de Barros
Undergraduate Student
Debora Brandt
Undergraduate Student
Luisa Kfouri Ribeiro
Undergraduate Student
Contact
Departamento de Bioquímica
Instituto de Química
Bloco 10 superior
Av. Prof. Lineu Prestes, 748
CEP 05508000
São Paulo, SP
Brazil
Phone: 55-11-30911201
bmalnic@iq.usp.br
Lab phone number: 55-11-30911202
