Pasaje Harrington 287 Harrington Pasaje Ancha Playa Chile Valparaíso, +56 32 2508040 www.cinv.cl Proc. Natl. Acad. Sci. Acad. Natl. Proc. . USA Sci. Acad. Natl. Proc. (2014). A,(2014). Neely Olcese R a cia Centro Centro PUBLICATIONS . 289(51):35438-54. (Selected as JBC as JBC (Selected . 289(51):35438-54. Chem Biol J cien de Neuro o io ciplinar Interdis . 111(27):9673-74. (2015). Mechanism of potassium ion M (2015). Mechanism and Holmgren SELECTED Functional heterogeneity of the four voltage sensors of a of the four voltage heterogeneity Functional L-typehuman channel. calcium 111(51):18381-6. Latorre O, Alvarez González C, JP, Castillo Raddatz N, coupling to channel and voltage R (2014).Temperature 8 potential melastatin receptor opening in transient (TRPM8). paper of the week). In pursuit of an inhibitory Pupo A & González C (2014). (Hv1). channel proton the for drug USA J, H, Wu Moldenhauer JO, R, Sosa-Pagán Goyal S, Jabba A, J Grandl R, Patapoutian M, Latorre Bandell Kalmeta B, in Mouse Activation of Temperature Directionality (2014). Single-Point by Channel Can Be Inverted Ion TRPA1 . 82(5):1017-1031. Six. Neuron in Ankyrin Repeat Mutations R, Bezanilla Latorre B, Roux H, BasilioD, Rui JP, Castillo, F 24 6:7622 . July Comm Nature Na+/K-ATPase. by uptake González C and H, Miño G, I, Poblete Diaz-Franulic in Thermally and Structure Allosterism R (2016). Latorre Rev. Channels Ann. Potential Receptor Transient Activated . 45:371-398 Biophys IE, Pupo A,Pinto BI, García MA, Retamal AD, Martinez at residues Charged R and Gonzalez C (2016). Latorre the voltage contribute to region transmembrane first the 291:15740-52 Chem J Biol gate. slow dependence of connexins , Larsson HP (2013). Subunit C, Larsson HP (2013). Subunit González S, Rebolledo Qiu F, opening of voltage-gated cooperative during interactions . 77(2):288-98. Neuron channels. proton D, Sigg N, A, Savalli Pantazis de Valparaíso DAD UNIVERSI - - - +-ac 2 + channels, + channels, 2 and and Francisco Bezanilla (University of Bezanilla (University Francisco This line of research aims to reveal mechanisms that aims to reveal This line of research 1 LINE Structure molecular of function sensors al investigators Principal Chicago), Miguel Holmgren (NIH, USA), Osvaldo Alvarez Alvarez Osvaldo (NIH, USA), Chicago), Miguel Holmgren of Mia- (University Larsson Peter de Chile), (Universidad Olcese Riccardo University), Tech Cuello (Texas mi), Luis of California at LA). (University Ramón Latorre, Alan Neely, Carlos González. Alan Neely, Ramón Latorre, rs Co-investigato and in connexins. They have succeeded in detecting gating detecting in succeeded have They connexins. in and domain of an extracellular and movements in Hv currents with research (together using VCF (Cx) by in a connexin also found that the TRPM8 channel (a They have line 2). - tempera decreasing can be opened only by cold receptor) and pathways a temperature-independent through ture of the phophati- identified the molecular nature have we channel binding site in TRPV1 dylinositol 4,5-biphosphate (a heat receptor). lead to ion channel opening in response to stimuli such as such to stimuli lead to ion channel opening in response calcium concen- changes in electric potential, intracellular are we present At temperature. or environmental tration there (a) Is questions: the following attempting to answer potential (TRP) receptor sensor in transient a temperature (b)and nature? its molecular is what And if so, channels? is or thermal energy the electrical, chemical (c) How opening)? pore (the energy into mechanical transformed using electro are we these questions to answer In order fluorescence clamp), patch y clamp (voltage physiological and volt –LRET- transfer (lanthanide energy resonance modeling and molecular age-controlled fluorometry-VCF), - line 5). Our research with research techniques (together voltage of functioning the on studies out carried have ers and Ca in voltage- (Hv), channels sensors in proton tivated K+ channels, in voltage-dependent K+ channels, tivated Ca
RESEARCH LINES LISH ENG González C, González Pasaje Harrington 287 Harrington Pasaje Ancha Playa Chile Valparaíso, +56 32 2508040 www.cinv.cl 19(8): Cell Biol Mol a cia Centro Centro (2012). Critical role of role Critical (2012). AD Martínez (2008). The connexin hemichannel (2008). The connexin Sáez JC cien de Neuro o io ciplinar Interdis , Araya-Secchi R, Lagos CF, Perez-Acle T, Berthoud T, Perez-Acle , Araya-Secchi R, Lagos CF, Investigator from the Pontificia Universidad Católica de Chile (PUC). Universidad the Pontificia from Investigator 1 Schalper KA, Palacios-Prado N, Retamal MA, Shoji KF, MA, Retamal KF, Shoji N, KA,Schalper Palacios-Prado AD, Martínez composition determines the FGF-1-induced membrane membrane composition determines the FGF-1-induced responses. Ca2+i free and permeability 3501–3513. Haro-Acuña F, AM, Momboisse González-Jamett AM (2013). Cárdenas P, JA, Caviedes Bevilacqua V, secretory the along dysfunction and function Dynamin-2 4:126. Endocrinol Front pathway. Sáez V, Figueroa J, Maripillán IE, R, García Acuña O, Jara JC EC, Beyer VM, of Cx26 in regulating domain transmembrane the first 23(17):3299- Cell Biol oligomerization and function. Mol 3311. Ory MJ, Guerra F, AM, Momboisse González-Jamett E, Couve S, Houy Calco V, N, X, Barraza Báez-Matus S, (2013). AM Cárdenas AD, Gasman S, A, Martínez Neely and quantal expansion fusion pore regulates Dynamin-2 actin dynamics a mechanism that involves through release PLoS One 8(8):70638. cells. chromaffin in neuroendocrine Ceriani R, Palacios-Muñoz O, Jara J, IE, Maripillán García T, Perez-Acle P, Olivero A,J, Ramachandran (2015). Keratitis- AD JE, Martínez , Contreras Sáez JC ichthyosis-deafness Cx26 mutants syndrome-associated but hyperactive gap junctions nonfunctional produce J hemichannels when co-expressed with wild type Cx43. Dermatol 135(5): 1338-47. Invest de Valparaíso DAD UNIVERSI - - Helmut Sánchez. Helmut (2013). De (2013). R, Sáez JC Latorre , Ana María Cárdenas, Agustín Martínez. Agustín Cárdenas, , Ana María 1 PUBLICATIONS 110(40):16229-16234. This line studies the molecular mechanisms underly This line studies 2 r investigato oung LINE Cell signaling al Investigators Principal SELECTED Juan Carlos Sáez Juan Y XF, BA, M, Figueroa Cisterna Cea LC, Frank C, Puebla K, Willecke C, Cardozo hemichannels in denervated of connexin expression novo Sci Acad Natl Proc muscles leads to atrophy. skeletal fast USA - electrophysi molecular, combining By signaling. cell ing techniques, ological, molecular dynamics and fluorescence (1) issues: following the on light shed have researchers our in oligomerization and involved the molecular structures which form hemichan- 26 and 43, function of connexins These channels mediate nels and gap junction channels. and some muta- pathways, communication intercellular non- and syndromic cause can genes coding their in tions of the role studied we In the brain, (2) deafness. syndromic of neu- hemichannels in inflammatory responses connexin chan- of pannexin diseases; (3) new roles rodegenerative neural synaptic plasticity, nels in cellular communication, and potentiation of skeletal neurosecretion, excitability, a GT dynamin-2, also studied We (4) muscle contraction. cortactin in controlling for endocytosis, responsible Pase as well release of transmitter dynamics during the process on which cause myopathies, as mutations in dynamin-2, needed for skeletal of proteins transport the intercellular muscle metabolism.
RESEARCH LINES LISH ENG ENGLISH Pasaje Harrington 287 Centro Playa Ancha Valparaíso, Chile Interdisciplinario +56 32 2508040 de Neurociencia UNIVERSIDAD de Valparaíso www.cinv.cl RESEARCH LINES LINE 3
Genetics and neural system development
Researchers in this line have shown that, in early de- (2015). Zebrafish adult-derived hypothalamic neurosphe- velopment, environmental odors can inhibit the expres- res generate gonadotropin-releasing hormone (GnRH) sion of olfactory receptors, and are currently exploring the neurons. Biol Open. 4(9):1077-86 mechanisms underlying this epigenetic interaction. They have found that adult stem cells can generate endocrine Torres-Paz J and Whitlock K.E. (2014). Olfactory sensory cells that are essential during puberty. This observation system develops from coordinated movements within the was made by using the zebrafish as a model system, and led neural plate. Dev Dyn. 2014 Dec;243(12):1619-31. to the initiation of a joint collaboration to analyze the genes involved in Kallmann syndrome. Toward gaining a better Diao F, Mena W, Shi J, Park D, Diao F, Taghert P, Ewer J understanding of how neuropeptides regulate expression and White BH (2016). The Splice Isoforms of the Droso- in sequential behavior, researchers have genetically coded phila Ecdysis Triggering Hormone Receptor have develop- Ca2+ markers in Drosophila. They have also gained great- mentally distinct roles. Genetics. 202(1): 175-189. er insight into how the circadian clock imposes a daily rhythm on behavior. A new research line is exploring how Krüger E, Mena W, Lahr EC, Johnson EC and Ewer J environmental parameters and diet such as the presence or (2015). Genetic analysis of Eclosion hormone action du- absence of food, and the presence of specific foods, change ring Drosophila larval ecdysis. Development. 142(24): 4279- animal’s behavior. Currently, the group is working on iden- 4287. tifying discrete elements of diet that provoke a change in behavior and the molecular targets in the host that change Diao F, Ironfield H, Luan H, Diao F, Shropshire WC, Ewer their expression to bring about the behavioral change. To J, Marr E, Potter CJ, Landgraf M and White BH (2015). this end, they use C. elegans as a model organism employ- Plug-and-Play Genetic Access to Drosophila Cell Types ing strategies that include functional genomics, behavioral using Exchangeable Exon Cassettes. Cell Rep. 10(8): 1410- assays, molecular and cellular techniques and OMICS ap- 1421. proaches. Lahr EC, Dean D, Ewer J (2012). Genetic analysis of ecdy- Principal Investigators sis behavior in Drosophila reveals partially overlapping functions of two unrelated neuropeptides. J. Neurosci. Kathleen Whitlock, John Ewer, Andrea Calixto1. 32(20): 6819-29.
SELECTED PUBLICATIONS Calixto A. (2015) Life without food and the implications for neurodegeneration. Advances in Genetics, Volume 92. Calfún C, Dominguez C, Pérez-Acle T and Whitlock KE (2016). Changes in olfactory receptor expression are corre- Kelley M, Yochem J, Krieg M, Calixto A, Heiman MG, lated with odor exposure during early development in the Kuzmanov A, Meli V, Chalfie M, Goodman MB, Shaham S, zebrafish (Danio rerio). Chem Senses. 41(4):301-12. Frand A, Fay DS. (2015) FBN-1, a fibrillin-related protein, is required for resistance of the epidermis to mechanical Whitlock KE (2015). The loss of scents: Do defects in deformation during C. elegans embryogenesis. eLife Mar olfactory sensory neuron development underlie human 23;4. disease? Birth Defects Research Part C: Embryo Today: Re- views 105(2):114-25
Cortes-Campos C, Letelier J, Ceriani R and Whitlock KE 1 Investigator from the Universidad Mayor, Chile. . and A.G J Neurosci. 2016 2016 J Neurosci. Pasaje Harrington 287 Harrington Pasaje Ancha Playa Chile Valparaíso, +56 32 2508040 www.cinv.cl a cia Centro Centro cien de Neuro o io ciplinar Interdis Kirkwood A. Kirkwood P, , Gallagher M, Worley nt publications ecent r Selected Dr. Chiayu Q. Chiu, the first Researcher Leader of CINV- Researcher Chiu, the first Q. Chiayu Dr. in also participate Group Planck Research Max Tandem this Line. Elgueta, C., Vielma, A.H.,, Vielma, Elgueta, C., Palacios induces (2015). Acetylcholine O. Schmachtenberg, heteromeric bipolar cells through onto rod release GABA Front. in A17 amacrine cells. expressed nicotinic receptors doi: 10.3389/fncel.2015.00006. 9(6):1-11, Neurosci. Cell. of a Form Induce Glutamate Receptors Metabotropic Signaling in the and Arc Translation by Controlled LTP T, Tran S, , Yang AO H, Ardiles Wang Hippocampus. Palacios M, Chuang YA, Baek G, R, Valdivia Posada-Duque AG doi: 10.1523/JNEUROSCI.0878-15.2016. 3;36(5):1723-9. Feb Morimoto-tomita A.E* Chávez , Mineur YS., J.*, Park P.E., Castillo M.R., Picciotto K.S., Kim S., Lutzu M., γ-8 CaMKII phosphorylation of TARP (2016) S. Tomita *Equal and Learning and Memory. is a mediator of LTP Oct 5;92(1):75-83. 2016 doi: 10.1016/j. Neuron. Contribution; neuron.2016.09.002. LM, Timpano JR, Rubenstein PR, Wendland Moya GA,KR, Heiman Tischfield JA, King RA, Andrews DL (2013) Murphy FJ, McMahon S, AM, Ramamoorthy transporter alleles of the serotonin Common and rare Mov. disorder. associated with Tourette’s SLC6A4, gene, doi: 10.1002/mds.25460 28(9):1263-70. Disord. de Valparaíso DAD UNIVERSI - Alfredo Kirkwood Kirkwood Alfredo Álvaro Ardiles. Álvaro Using a variety of cellular and molecular tools, com- of cellular and molecular tools, a variety Using 4 r investigato oung LINE ms Systems and Circuits Neuroscience al Investigators Principal (Johns Hopkins University). Hopkins (Johns Y Adrián G. Palacios, Oliver Schmachtenberg, Andrés E. Schmachtenberg, Oliver Palacios, G. Adrián R. Moya. Pablo Chávez, rs Investigato Associated bined with electrophysiology and behavior, we are interest are we and behavior, bined with electrophysiology transformed are stimuli external how ed in understanding we date, To behaviors. to generate circuits our neural by - disease pres of Alzheimer’s found that “biomarkers” have also present during aging are brain ent in the degus rodent function. its normal physiological affecting in the retina, in identifying the mechanisms by also interested are We within is altered plasticity which the capacity for neuronal in developing stress following circuits neuronal different of participation found a differential we Of note, rodents. popu- neuronal recording By receptors. and NMDA AMPA histological with combined units, cell single and lations the encoding of studying are we and imaging techniques, circuits and brain sensory information in both the retina (ol- In the olfactory system hippocampus. and cortex like role the investigate we teleost), cerebrum and bulb factory as a new as well of ubiquitous field potential oscillations, we Finally, nitric oxide. mediated by pathway regulatory the cellular and molecular in investigating interested are diseases, neurological specific that underlie mechanisms - new knowl to provide in order such as mood disorders, of new therapies edge that will facilitate the development of these diseases. for the treatment
RESEARCH LINES LISH ENG
Pasaje Harrington 287 Harrington Pasaje Ancha Playa Chile Valparaíso, +56 32 2508040 www.cinv.cl a cia Centro Centro cien de Neuro o io ciplinar Interdis Investigator at Fundación Ciencia & Vida. at Fundación Investigator Investigator at Universidad Andrés Bello. at Universidad Investigator 1 2 113(23):E3231-9 N, R, Navarro-Quezada I., Sepúlveda Díaz-Franulic, dimensions D (2015). Pore FD and Naranjo González-Nilo of occupancy in unitary conductance of Shaker and the role 146:133-146. J Gen Physiol K-channels. FD, I, González-Nilo H, Díaz-Franulic Moldenhauer of and radius size pore Effective D (2016). Naranjo 6:19893. Sci Rep. for K+ ions in K-channels. capture M and Díaz- H, Pincuntureo D, Moldenhauer Naranjo size matters for potassium channel Pore I (2016). Franulic 148(4):277-91. J Gen Physiol conductance. Poblete H, Oyarzún I, Olivero P, Comer J, Zúñiga M, J, Comer P, I, Olivero H, Oyarzún Poblete González León C, González- D, Báez-Nieto RV, Sepúlveda determinants of R (2015). Molecular FD, Latorre Nilo binding (PI(4,5)P2) phosphatidylinositol 4,5-bisphosphate J Biol channels. potential V1 (TRPV1) receptor to transient . 290(4):2086-98. Chem González- V, MI, Marabolí Niemeyer Cornejo I, Andrini O, Cid LP (2015). FV, Sepúlveda J, FD, Teulon Nilo of a glutamate- and functional expression Identification Caligus from channel chloride and avermectin-gated affecting louse sea Hemisphere southern a rogercresseyi, 2086-98. . 290(4): farmed fish. PLoS Pathog Bernardin T, Huynh T, Kang S, Araya-Secchi R, Pérez-Acle , Sáez JC I, A, García Martínez A, Escalona Y, JA, Garate pocket water of a novel Characterization Zhou R (2014). J. Biophys inside the human Cx26 hemi-channel structure. 107(3):599-612. Diffusion approximation- Orio P (2014). Soudry D, D, Pezo ion channels: which method based simulation of stochastic . 8:139. Neurosci Comput to use?. Front R, Zhou T, Huynh R, Araya-Secchi JA, Garate Y, Escalona potential the membrane Exploring T (2016). Pérez-Acle Gap- as models for systems of simple dual-membrane J. 110(12):2678-88 Biophys. junction channels. Campos G, Herrera JP, Maidana S, Salgado E, Olivares P (2015). TRPM8-Dependent R, Orio M, Madrid of Cold Model in a Mathematical Dynamic Response 10:e0139314. PLOS One. Thermoreceptor. CA, Zaelzer HC, Hyde JE, Sánchez-Rodríguez JP, Castillo Gonzalez-Nilo SB, Kent LY, Luk RV, Sepúlveda D, Aguayo β1-subunit-induced R (2016) Latorre FD, Bezanilla F, voltage- and Ca2+- the of rearrangements structural Sci U S A. Acad Natl channel. Proc K+ (BK) activated de Valparaíso DAD UNIVERSI , - - - 2 José Antonio Garate Antonio Garate José Ricardo Cabrera (Universidad de (Universidad Cabrera Ricardo , David Naranjo, Tomas Pérez-Acle Tomas Naranjo, , David 1 108(11):3009-3023. J Neurophysiol 5 r investigato oung LINE ular simulation simulation Molecular computational and biology d publications Selected al investigators Principal Chile), Alberto J. Martín (Fundación Ciencia & Vida) (Fundación Martín Chile), Alberto J. Danilo González-Nilo Danilo Y rs Co-investigato F Viana Belmonte C, A, R, González O, Madrid P, Parra Orio Cold of Mammalian Pattern of Ih in the Firing Role (2012). Thermoreceptors. tivation, neural dynamics and neural networks. They have They have networks. dynamics and neural neural tivation, located in the cyto pocket a water discovered recently 26 hemichannel that is connexin of human plasmic region a specific proposing also functioning, crucial for its proper with- of voltage in the presence distribution for charge role - theoreti an iterative Likewise, of this channel. in the pore of feedback permitted the extraction cal and experimental for K+ channels (Shaker relationships structure-function In particu- as for TRP and Ca2+ channels. and BK), as well site in TRPV1 identified the PIP2 binding they have lar, to contributed have our researchers channel. Moreover, de dimensions of the pore the physical how understand On the other in potassium channels. termine ion transport Line channels, of TRPV1 analyses structural hand, trough adaptation identified the temperature have 5 researchers living in the Equator and the South of penguins process researchers our excitability, neural of area the Within Pole. the of contribution the interpreted mathematically have studied have and sensation cold acute to channel TRPM8 simulation methods applied to neuroscience. stochastic Investigators working in this line have applied advanced advanced applied in this line have working Investigators simula- methods of mathematical modeling and molecular communication, ion channel ac intercellular tion to study (Fundación Ciencia & Vida) Ciencia & Vida) (Fundación Patricio Orio. Orio. Patricio
RESEARCH LINES LISH ENG