Line 1: Structure and function of molecular sensors.
1- This research line focuses on studying how the external environment influences channels present on the cell membrane that open or close depending on the external stimuli. In mammals, these channel determine processes as relevant as hormone secretion and neurotransmitters sensory transduction and muscle and nerve excitation. This group studies how changes in the electrical potential (field) of the cell membrane or changes in the environmental temperature affect the cold-hot sensation with the idea of determining the structure of the temperature sensor and observe how electrical, chemical or thermal energies transform in mechanical energy (which will in turn causing the opening of the channels). Researchers in this group investigate the functioning of different sensors present in the channels and hemichannels that are formed by connexins, a protein family that establish communication bridges between cells and that are very necessary for the correct functioning of the organisms. To answer these questions different electrophysiological techniques are used in order to analyze the electrical properties of the cells, from unique channels in individual cells to whole organs using the Xenopus as a model system. This line also uses fluorescence and computational model techniques in collaboration with line 5.
Researchers.
- Ramón Latorre / fono:(56) 32 2508029 / ramon.latorre@uv.cl
- Alan Neely / fono:(56) 32 2995676 / alan.neely@uv.cl
- Francisco Bezanilla / fono:(1) 773 8341458 / fbezanilla@uchicago.edu
- Ignacio Díaz / fono: (56) 32 2508040 / ignacio.diaz@unab.cl
- Isaac García / fono: (56) 32 2508556 / isaac.garcia@uv.cl
- José Gárate / fono: (56) 32 2508040 / jose.garate@uv.cl
- Karen Castillo / fono:(56) 32 2508189 / karen.castillo@cinv.cl
Associate Researchers.
- Miguel Holmgren / fono: (1) 301 4516259 / holmgren@ninds.nih.gov
- Osvaldo Alvarez / fono:(56) 32 2508190 / oalvarez@uchile.cl
Postdoctoral Researchers.
PhD Students.
- Antonio Peña / fono: (56) 32 2508088 / antonio.pena@cinv.cl
- Christian Carrillo / fono: (56) 32 2508088 / christian.carrillo@cinv.cl
- Daniela De Giorgis / fono:(56) 32 2508051 / daniela.degiorgis@cinv.cl
- Felipe Echeverria / fono:(56) 32 2508190 / felipe.echeverria@cinv.cl
- Guido Mellado / fono: (56) 32 2508051 / guido.mellado@cinv.cl
- Jonathan Saavedra / fono: (56) 32 2508051 / toti776@hotmail.com
- Juan Alvear / fono: (56) 32 2508088 / j.alveara@gmail.com
- Juan Ferrada / fono:(56) 32 2508190 / juan.ferrada@postgrado.uv.cl
- Karina Carvajal / fono: (56) 32 2508190 / karicat.c@gmail.com
- Miguel Fernández / fono: (56) 32 2508088 / miguel.fernandez@postgrado.uv.cl
- Naileth González / fono: (56) 32 2508190 / naileth.gonzalezs7@gmail.com
- Rosangelina Alvarado / fono:(56) 32 2508190 / rosangelina.alvarado@postgrado.uv.cl
- Asuaje A, Smaldini P, Martín P, Enrique N, Orlowski A, Aiello EA, Gonzalez León C, Docena G, Milesi V. (2017) The inhibition of voltage-gated H+ channel (HVCN1) induces acidification of leukemic Jurkat T cells promoting cell death by apoptosis. Pflugers Arch. 469(2):251-261. doi: 10.1007/s00424-016-1928-0.
- Alvarez O and Latorre R. 2017. The enduring legacy of the “constant-field equation” in membrane ion transport. J Gen Physiol. 2017 Oct 2;149(10):911-920. doi: 10.1085/jgp.201711839Qiu F, Rebolledo S, González C, Larsson HP (2013). Subunit interactions during cooperative opening of voltage-gated proton channels. Neuron. 77(2):288-98.
- Latorre R, Castillo K, Carrasquel-Ursulaez W, Sepulveda RV, Gonzalez-Nilo F, Gonzalez C and Alvarez O. (2017). Molecular determinants of BK channel functional diversity and functioning. Physiological Reviews, 97(1):39-87.
- Raddatz N, Castillo JP, González C, Alvarez O, Latorre R (2014).Temperature and voltage coupling to channel opening in transient receptor potential melastatin 8 (TRPM8). J Biol Chem. 289(51):35438-54. (Selected as JBC paper of the week).
- Castillo, JP, Rui H, BasilioD, Roux B, Latorre R, Bezanilla F and Holmgren, M (2015). Mechanism of potassium ion uptake by Na+/K-ATPase. Nature Comm. July 24 6:7622
- Fernández A, Pupo A, Mena-Ulecia K and Gonzalez C, (2016) Pharmacological modulation of proton channel Hv1 in cancer therapy: Future perspectives Mol Pharmacol Sep;90(3):385-402. doi: 10.1124/mol.116.103804.
- García IE, Bosen F, Mujica P, Pupo A, Flores-Muñoz C, Jara O, Gonzalez C, Willecke K and Martinez AD (2016) From Hyperactive Connexin26 Hemichannels to Impairments in Epidermal Calcium Gradient and Permeability Barrier in the Keratitis-Ichthyosis-Deafness Syndrome J Invest Dermatol 136(3):574-83.
- Pinto BI, García IE, Pupo A, Retamal MA, Martinez AD, Latorre R and Gonzalez C (2016). Charged residues at the first transmembrane region contribute to the voltage dependence of connexins slow gate. J Biol Chem 291:15740-52.
- Castillo JP, Sánchez-Rodríguez JE, Clark Hyde H, Zaelzer CA, Aguayo D, Sepúlveda R, Luk LYP, Kent S, Gonzalez-Nilo F, Bezanilla F, and Latorre R. (2016) β1 Subunit-Induced Structural Rearrangements of the Ca2+- and Voltage-Activated K+ (BK) Channel. Proc. Natl Acad Sci (USA). 113(23):E3231-9. doi: 10.1073/pnas.1606381113.
- Diaz-Franulic I, Poblete H, Miño G, Gonzalez C, and Latorre R (2016) Allosterism and Structure in Thermally Activated Transient Receptor Potential Channels Ann. Rev. Biophys. 45:371-98. doi: 10.1146/annurev-biophys-062215-011034.
- García IE, Prado P, Pupo A, Jara O, Rojas-Gómez D, Mujica P, Flores-Muñoz C, González-Casanova J, Soto-Riveros C, Pinto BI, Retamal MA, Gonzalez C and Martinez AD (2016) Connexinopathies: a structural and functional glimpse. BMC Cell Biology May 24;17 Suppl 1:17. doi: 10.1186/s12860-016-0092-x
Ongoing projects.
INSTITUTO MILENIO-CINV
Año: 2016-2021
Concurso: Proyectos Institutos Milenio 2009 – ICM09-022-P
Financiamiento: Ministerio de Economía, Fomento y Turismo de Chile
Investigador Principal: Ramón Latorre
Otros Investigadores: Juan Carlos Sáez, Alan Neely, Ana María Cárdenas, John Ewer, Kathleen Whitlock, Adrián Palacios, Tomás Pérez-Acle, David Naranjo, Fernando González-Nilo, Oliver Schmachtenberg, Agustín Martínez, Patricio Orio, Andrés Chávez, Pablo Moya, Andrea Calixto, Carlos González.
Otras Universidades o Instituciones: Centro Interdisciplinario de Neurociencia de Valparaíso, Pontificia Universidad Católica, Universidad Andrés Bello, Fundación Ciencia y Vida.
MECHANISM OF VOLTAGE GATING IN CA+2 AND VOLTAGE-ACTIVATED (BK) CHANNELS
Año: abril 2023 – marzo 2027
Concurso: Fondecyt Regular 1230265
Financiamiento: Agencia Nacional de Investigación y Desarrollo (ANID)
Investigador Principal: Ramón Latorre
Otros Investigadores:
Otras Universidades o Instituciones:
IDENTIFICATION OF THE STRUCTURAL DETERMINANTS OF TOXIN SNX-482 BINDING TO CAV2.3 AN KV4.3 CHANNELS AND DESIGN OF CAV2.3 SELECTIVE VARIANT
Año: abril 2023 – marzo 2027
Concurso: Fondecyt Regular 1231482
Financiamiento: Agencia Nacional de Investigación y Desarrollo (ANID)
Investigador Principal: Alan Neely
Otros Investigadores:
Otras Universidades o Instituciones:
DECIPHERING THE ROLE OF THE IVS-LOOP ON THE VOLTAGE-SENSING MECHANISM OF THE INNER-EAR AREA MOTOR PROTEIN PRESTIN
Año: abril 2023 – marzo 2027
Concurso: Fondecyt Regular 1231164
Financiamiento: Agencia Nacional de Investigación y Desarrollo (ANID)
Investigador Principal: Raúl Araya (PI)
Otros Investigadores: Isaac García (CoPI)
Otras Universidades o Instituciones: Universidad San Sebastián
EXPLORING THE ROLE OF TRANSMEMBRANE VOLTAGE AND ECTRACELLULAR Ca2+ ON THE THERMODYNAMIC EQUILIBRIUM BETWEEN THE OPEN AND CLOSED STATES OF THE HUMAN Cx26 HEMICHANNEL
Año: abril 2021 – marzo 2025
Concurso: Fondecyt Regular 1211045
Financiamiento: Agencia Nacional de Investigación y Desarrollo (ANID)
Investigador Principal: Tomás Perez Acle (Ciencia & VIda)
Otros Investigadores:Isaac García, Agustin Martínez
Otras Universidades o Instituciones: Fundación Ciencia & VIda
NUCLEUS IN NANOBIOPHYSICS (NNBP)
Año: marzo 2022 – marzo 2025
Concurso: Núcleos Milenio Ciencias Naturales y Exactas NCN2021_021
Financiamiento: Agencia Nacional de Investigación y Desarrollo (ANID)
Investigador Principal: José Antonio Gárate,
Otros Investigadores: Carlos Gonzalez y Eduardo Berrios
Otras Universidades o Instituciones:
THE THERMODYNAMICS OF NANOCONFINEMENT IN SYNTHETIC AND BIOLOGICAL CHANNELS: FROM STRUCTURE TO FUNCTION
Año: abril 2022 – marzo 2026
Concurso: Fondecyt Regular 1221260
Financiamiento: Agencia Nacional de Investigación y Desarrollo (ANID)
Investigador Principal: José Antonio Gárate,
Otros Investigadores:
Otras Universidades o Instituciones:
TEMPERATURE SENSING ON THE TRPM CHANNELS FAMILY: UNVEILING THE ROLE OF A FOLDING/UNFOLDING REACTION AT THE C-TERMINUS DOMAIN
Año: abril 2022 – marzo 2026
Concurso: Fondecyt Regular 1221498
Financiamiento: Agencia Nacional de Investigación y Desarrollo (ANID)
Investigador Principal: Danilo Gonzalez (Andrés Bello)
Otros Investigadores: Ramón Latorre
Otras Universidades o Instituciones: Universidad Andrés Bello
THE ELECTROPHYSIOLOGICAL STUDIES OF VOLTAGE GATED CHANNELS
Año: abril 2022 – marzo 2026
Concurso: NIH Research Project Grant (RO1 ) R01GM030376
Financiamiento: National Institutes Of Health (NIH)
Investigador Principal: Francisco Bezanilla (University of Chicago)
Otros Investigadores: Ramón Latorre
Otras Universidades o Instituciones: University of Chicago
CENTRO INTERDISCIPLINARIO DE NEUROCIENCIA DE VALPARAÍSO ANID.
APOYO A CENTROS DE EXCELENCIA
Año: abril 2022 – marzo 2026
Concurso: ACE210014
Financiamiento: Agencia Nacional de Investigación y Desarrollo (ANID)
Investigador Principal: Juan Carlos Sáez
Otros Investigadores: Alan Neely, Ana María Cárdenas, John Ewer, Kathleen, Whitlock, Adrián Palacios, Fernando Danilo González-Nilo, Oliver
Schmachtenberg, Agustín Martínez, Patricio Orio, Andrés Chávez, Pablo Moya, Andrea Calixto, Carlos González
Otras Universidades o Instituciones:
