 Nombre:
Juan Domingo Bacigalupo Vicuña.
Grado:
Licenciado en Biología, 1975
Universidad de Chile (UCH), CHILE
Ph.D. en Biología, 1983
Brandeis University, Estados Unidos
Temas investigación.
Our laboratory is interested on the mechanisms underlying sensory transduction, particularly of light and odors. Our model systems are Drosophila photoreceptors and rat and toad olfactory receptor neurons (ORNs). In both cases the sensory stimulus activates a G-protein-coupled receptor, triggering a protein cascade that mediates the opening of ion channels, generating a receptor potential. The components of the cascades are confined to highly specialized organelles, microvilli in photoreceptors and cilia in ORNs. Although the constituents of the respective cascades are known, there are fundamental questions that we are trying to answer. This goal demands a multidisciplinary approach including electrophysiology, immunochemistry, fluorescence microscopy, biochemistry, molecular biology and computational modeling. We developed the unique expertise of recording single-channel currents from extremely small structures, such as cilia and microvilli. We have been using single-channel recordings no only to characterize the transduction channels in their native membranes, but also to examine the final steps of both transduction processes. Drosophila phototransduction involves a diacylglycerol cascade that opens the TRP and TRPL light-dependent channels. We have been studying such channels and the identity of their agonist, thought to be a membrane lipid. Odor transduction entails a cAMP cascade that targets a cyclic nucleotide-gated channel and a Ca2+-activated Cl- channel (ClCa). We are studying the ClCa channel, of unknown molecular identity. We are trying to understand the organization of the cascade within a cilium. We are also investigating Ca2+, an ion with a crucial role in this process. We investigate the mechanisms relevant to ciliary Ca2+ dynamics with fluorescence microscopy, electrophysiology and other methods. Our intention is to develop a dynamic model of Ca2+ homeostasis. Our long term goal is to understand how the olfactory cilium works. We are also investigating the properties of the neurons and neuronal circuits of the olfactory cortex of the amygdala.
Research interest.
Nuestro laboratorio está interesado en los mecanismos subyacentes de la transducción sensorial, particularmente de la luz y olores. Nuestros sistemas de modelo son fotorreceptores de Drosophila y neuronas receptoras olfatorias de rata y de sapo (ORNs). En ambos casos el estímulo sensorial activa un receptor acoplado a proteína G, desencadenando una cascada de proteína que media la apertura de canales iónicos, generando un potencial de receptor. Los componentes de las cascadas se limitan a organelos altamente especializados, microvellosidades en fotorreceptores y cilios en ORNs. Aunque se conocen los constituyentes de las cascadas respectivos, hay preguntas fundamentales que estamos tratando de responder. Este objetivo exige un enfoque multidisciplinario, incluyendo electrofisiología, inmunoquímica, microscopía de fluorescencia, bioquímica, biología molecular y modelamiento. Hemos desarrollado la experiencia única de la grabación de las corrientes de un canal de estructuras extremadamente pequeñas, tales como cilios y microvellosidades. Hemos estado utilizando registros de canal único no sólo para caracterizar los canales de transducción en sus membranas nativos, sino que también para examinar los pasos finales de ambos procesos de transducción. La fototransducción en Drosophila envuelve una cascada de diacilglicerol, la cual lleva a la apertura de los canales de luz-dependientes PRT y TRPL. Nosotros hemos estado estudiando esos canales y la identidad de su agonista, el cual se piensa que es un lípido de la membrana de la microvellosidad. La transducción de olor una cascada de AMPc que tiene como blanco a un canal activado por de nucleótidos cíclicos (AMPc) y otro de Cl- activado por Ca2+ (ClCa). Estamos estudiando este último, cuya identidad molecular se desconoce. Estamos intentando comprender la organización de la cascada que opera en el cilio. Estamos también investigando Ca2+, un ion con un papel crucial en este proceso. Investigamos los mecanismos relevantes para la dinámica del Ca2+ ciliar con microscopía de fluorescencia, electrofisiología y otros métodos. Nuestra intención es desarrollar un modelo dinámico de la homeostasis Ca2+. Nuestro objetivo a largo plazo es entender cómo funciona el cilio olfatorio. También estamos investigando las propiedades de las neuronas y circuitos neuronales de la corteza olfatoria de la amígdala.
Distinciones y premios.
Doft Graduate Fellowship, Brandeis University. 1978‑1980.
Grass Foundation Fellowship. MBL, Woods Hole, MA, USA. 1984.
Tinker Foundation Fellowship. MBL, Woods Hole, MA. USA, 1985.
Cátedra Presidencial en Ciencias. 1997.
Medalla Rectoral, University of Chile. 1998.
Medalla Rectoral Professor Titular, University of Chile, 2000
Sir Allen Sewell Award, Griffith University, Brisbane, Australia. 2003
Fellow of the John S. Guggenheim Memorial Foundation, USA, 2006
Visiting Scholar, Griffith University, Brisbane, Australia. 2007
Member of the IBRO Workshop & Symposia Funding Programme Committee (2001-)
Member of the IBRO Nominating Committee (2009-)
Publicaciones desde 2004.
Delgado, R, Bacigalupo, J. 2004. Cilium-attached and excised patch-clamp recordings of odorant activated Ca2+dependent K+ channels from chemosensory cilia of olfactory receptor neurons. Eur. J. Neurosci. 20: 2975-2980.
Schmachtenberg, O, Bacigalupo, J. 2004. Olfactory transduction in ciliated receptor neurons of the Cabinza grunt, Isacia conceptionis (Teleostei: Haemulidae). Eur. J. Neurosci. 20: 3378-3386.
Castillo, K, Bacigalupo, J, Wolff, D. 2005. Ca2+-dependent K+ channels of rat olfactory cilia: Characterization in planar lipid bilayers. FEBS Lett.579: 1675-1682.
Ugarte G, O’Day PM, Bacigalupo J, Vergara C. 2005. A CLC-2-like chloride conductance in Drosophila photoreceptors. In Pumps, Transporters and Ion Channels, F. Sepulveda and F Bezanilla, Eds. Kluwer Academic/Plenum Publishers. Ch. 16, pp 157-164
Madrid, R, Delgado, R, Bacigalupo, J. 2005. A cyclic AMP cascade mediates the inhibitory odor response of isolated toad olfactory receptor neurons. J. Neurophysiol. 94: 1781-1788.
Sanhueza, M, Bacigalupo J. 2005. Intrinsic subthreshold oscillations of the membrane potential in pyramidal neurons of the olfactory amygdala. Eur. J. Neurosci. 22:1618-1626.
Ugarte, G, Delgado, R, O’Day, PM, Farjah, F, Vergara, C, Bacigalupo, J. 2005. A ClC-2-like chloride channel mediates inward rectification in Drosophila retinal photoreceptors. J. Memb. Biol. 207: 151-160.
Mura, CV, Delgado, R, Aguirre, P, Bacigalupo J, Núñez MT. 2006. Quiescence induced by iron challenge protects neuroblastoma cells from oxidative stress. J. Neurochem. 98: 11-19.
Brauchi S, Cea C, Bacigalupo J, Reyes, J. 2006. Apoptosis induced by prolonged exposure to odorants in cultured cells from rat olfactory epithelium. Brain Research. 1103: 114-122.
Sülz,L, Bacigalupo, J. 2006. Role of nitric oxide during neurogenesis in the olfactory epithelium. Biol. Research. 39: 589-599.
Diaz J, Razeto P, Letelier JC, Caprio J, Bacigalupo J. 2007. Amplitude modulation patterns of local field potentials reveal asynchronous neuronal populations. J. Neurosci. 27: 9238-9245.
Castillo K, Delgado R, Bacigalupo J. 2007. Plasma Membrane Ca2+-ATPase in the Cilia of Olfactory Receptor Neurons: Possible role on Ca2+ clearance. Eur J Neurosci. 26: 2524-2531.
Astorga G, Bacigalupo J. 2008. TRP channels as biological sensors. Physiological Mini-reviews 3: 25-33.
Saavedra MV, Smalla K-H, Thomas U, Sandoval S, Olavarria K, Castillo K, Delgado MG, Delgado R, Gundelfinger E, Bacigalupo J, Wyneken U. 2008. Scaffolding proteins are present in highly purified rat olfactory cilia membranes. NeuroReport. 19: 123-126.
Sülz, L, Astorga, G, Bellette B, Iturriaga, R, Mackay-Sim, A, Bacigalupo, J. Nitric oxide regulates neurogenesis in adult olfactory epithelium in vitro. 2009. Nitric Oxide B CH. 20: 238-252.
Delgado R, Bacigalupo J. 2009. Unitary recordings of TRP and TRPL channels from isolated Drosophila retinal photoreceptors rhabdomeres: Activation by light and lipids. J Neurophysiol 101:2372-2379.
Proyectos de investigación.
Millennium Institute for Cell Dynamics and Biotechnology. MIDEPLAN ICM P05-001-F. 2007-2012. Juan Asenjo, Director. Juan Bacigalupo, Key Investigator.
Participación de la Ca2+-ATPasa de cilios olfatorios en la remoción del Ca2+ luminar que ingresa durante la respuesta a odorantes. Proyecto 1080653. Principal Investigator. 2008-2010.
Signal transduction in TRPM5-expressing olfactory sensory neurons. FIRCA NIH 1R03TW007920-01A1 (USA). Diego Restrepo, Co-investigador. 2008-2011.
On search of the elusive Ca2+-dependent Cl- channel involved in odor transduction in olfactory cilia. Proyecto 1100682. Principal Investigator. 2010-2014.
Study of the light-transducción, light-adaptation and response deactivation mechanisms of Drosophila fotorreceptors by means of single-channel recordings from the photosensitive membrane.1100730. Co-investigator. 2010-2014.
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