Calcio y Función Celular
Embedded Files
Integrantes
Integrantes
Investigadores Principales:
Mª Teresa Alonso
Investigadores Doctores:
Jonathan Rojo
Javier García-Sancho
Belén Calvo Rodríguez
Investigadores Predoctorales:
Patricia Torres Vidal
Técnico de Laboratorio:
Jesús Fernández
Breve descripción del grupo
Our scientific interest focusses on the role of intracellular calcium (Ca2+) as a signaling molecule in various cellular paradigms and models, both in health and disease. The Ca2+ ion is the most universal and versatile intracellular messenger, necessary for very diverse functions, from muscle contraction to fertilization. In each cell many enzymes and regulatory proteins modulated by Ca2+ coexist and selectivity is achieved because many cellular processes are compartmentalized in specific microenvironments limited to subcellular organelles (nuclear transcription, protein synthesis in the endoplasmic reticulum (ER), mitochondrial respiration, etc.) or microdomains containing high concentrations of Ca2+. Our group was a pioneer in the establishment of micro-epifluorescence and Ca2+ imaging analysis in living cells in Spain, including single cell resolution and development of apparatuses, protocols, and methodologies (know-how) that has gained us an international reputation in the calcium signalling field.
In the last two decades our group has focused on the role of the cytosolic organelles in Ca2+ signaling, especially, ER, mitochondria, nucleus or, more recently, the endol-ysosome system. To address this, we have developed a number of novel genetic Ca2+ indicators optimized for organelles, both fluorescent and bioluminescent. Our research extends from a molecular level in vitro, using the purified Ca2+ indicator protein to explore mechanistic aspects of the structure-function relationship, up to the level of the organism, with the generation of transgenic animals and their application in vivo studies in physio-pathological aspects such as aging or neurodegeneration. For example, by monitoring Ca2+ in the sarcoplasmic reticulum (SR) of muscles in live flies we have discovered that the loss of muscle mass and strength associated to age is linked to a progressive reduction of [Ca2+] SR.
Some of our current lines of research are:
To investigate on the alterations in [Ca2+]ER homeostasis in a neurodegeneration model for Huntington's disease in Drosophila.
To identify the proteins that accumulate and release calcium across the endo-lysosomal system by using a novel Ca2+ indicator specifically developed for this organelle.
By using state-of-the-art Crisp/Cas9 technology, we have generated transgenic mice with conditional expression of the calcium sensor GAP3 in the ER. By crossing this line with specific Cre-deleters for pancreatic alfa- or beta-cells, we will analyse the role of ER Ca2+ within different physio-pathological scenarios.
Artículos más relevantes
Rojo-Ruiz, J., Calvo, B., Alonso, M.T. and García-Sancho, J. (2024). Using fluorescent GAP indicators to monitor ER Ca2+. Current Protocols Cell Biol. (in press).
Delrio-Lorenzo, A., Rojo-Ruiz, J., Torres-Vidal, P., Alonso, M.T. and García-Sancho, J. (2024). In vitro and in vivo calibration of low affinity genetic Ca2+ indicators. Cell Calcium. 117: 102819.
Alonso, M.T., Torres-Vidal, P., Calvo, B., Rodriguez, C., Delrio-Lorenzo, A., Rojo-Ruiz, J., Garcia-Sancho, J., and Patel, S. (2023). Use of aequorin-based indicators for monitoring Ca2+ in acidic organelles. BBA Mol Cell Res. 1870: 119481.
Gómez-Valadés AG, Pozo M, Varela L, … Alonso MT (18/26), …, Claret M. (2021) Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis. Cell Met. 33: 1820-1835.
Rojo-Ruiz, J., Navas-Navarro, P., Nuñez, L., García-Sancho, J., and Alonso, MT. (2020) Imaging of Endoplasmic Reticulum Ca2+ in the Intact Pituitary Gland of Transgenic Mice Expressing a Low Affinity Ca2+ Indicator. Front. Endocrinol. 11: 615777. doi: 10.3389/fendo. 615777.
Delrio-Lorenzo A, Rojo-Ruiz J, Alonso MT, García-Sancho J. (2020) Sarcoplasmic reticulum Ca2+ decreases with age and correlates with the decline in muscle function in Drosophila. J Cell Sci. 133: jcs240879.
Rodríguez-Prados M, Rojo-Ruiz J, García-Sancho J, Alonso MT. (2020) Direct monitoring of ER Ca2+ dynamics reveals that Ca2+ entry induces ER-Ca2+ release in astrocytes. Pflugers Arch. 472: 439-448.
Arduino DM, Wettmarshausen J, Vais H, Navas-Navarro P, Cheng Y, Leimpek A, Ma Z, Delrio-Lorenzo A, Giordano A, Garcia-Perez C, Médard G, Kuster B, García-Sancho JG, Mokranjac D, Foskett JK, Alonso MT, Perocchi F. (2017) Systematic identification of MCU modulators by orthogonal interspecies chemical screening. Mol Cell. 67: 711-723.
Navas-Navarro P, Rojo-Ruiz J, Rodriguez-Prados M, Ganfornina MD, Looger LL, Alonso MT and García-Sancho J. (2016) GFP-Aequorin Protein sensor for cell-based, ex vivo and in vivo imaging of Ca2+ dynamics in high Ca2+ organelles. Cell Chem Biol. 23: 738-45.
Rodriguez-Garcia A, Rojo J, Navas-Navarro P, Aulestia F, Gallego-Sandin S, Garcia-Sancho J, Alonso MT. (2014) GAP, a new aequorin-based fluorescent indicator for imaging Ca2+ in organelles. PNAS. 111: 2584-9.
Proyectos más relevantes
Título del proyecto: Bases moleculares y fisiológicas implicadas en la dinámica del calcio endolysosomal en condiciones de salud y enfermedad (PID2023-146434NB-I00).
Duración: 2024 – 2027.
Entidad financiadora: Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación y FEDER, UE.
Presupuesto: 325.000 €.
Investigador Principal: María Teresa Alonso Alonso.
Proyecto PID2020-116086RB-I00 y PID2023-146434NB-I00 financiados, respectivamente por:
2022-2024 Proyecto de Investigación financiado por el Ministerio de Ciencia e Innovación (PID2020-116086RB-I00) (340.000 €).
"Calcio y Función Celular".
IP: M.T. Alonso y J. García-Sancho.
2018-2021 Proyecto de Investigación financiado por el Ministerio de Ciencia e Innovación (BFU2017-83066-P) (363.000 €).
"Calcio y Función Celular".
IP: M.T. Alonso y J. García-Sancho.
2015-2027 Proyecto de Investigación financiado por el Ministerio de Ciencia e Innovación (BFU2014-53469-P) (423.000 €).
"Calcio y Función Celular".
IP: M.T. Alonso y J. García-Sancho.
Contacto
Page updated
Google Sites
Report abuse