INVESTIGADORES
BLAUSTEIN KAPPELMACHER Matias
congresos y reuniones científicas
Título:
Characterization of the unfolded protein response by fluorescent reporters in single cells
Autor/es:
DANIELA CHINY BARRIONUEVO; MARIELA VEGGETTI; ALEJANDRO COLMAN-LERNER; MATÍAS BLAUSTEIN
Lugar:
Mar del Plata
Reunión:
Congreso; LI Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2015
Institución organizadora:
SAIB
Resumen:
The Unfolded Protein Response (UPR) is a cellular stress signaling cascade activated by different signals such as accumulation of misfolded proteins in the Endoplasmic Reticulum (ER). This homeostatic response involves the activation of three parallel pathways: IRE1, PERK and ATF6, and promotes cell survival in the short term but stimulates apoptosis if misfolded protein levels remain high. The integration of the information derived from these sensors is essential for cell-fate decision making. In order to characterize UPR dynamics in human single cells, we developed a set of fluorescent reporters to monitor the activation of UPR pathways in real time, allowing us to analyze the dynamic shuttling of UPR components between different subcellular compartments and to measure cell-to-cell variation in the activation of UPR. We generated stable Hela Kyoto cell lines expressing these reporters and designed a protocol for automated imaging, segmentation and quantitative analysis of cells and UPR activation. Our goal is to find patterns that provide us with information about the state of the cell and which can be associated to a specific cell fate. Since UPR deregulation plays an important role in malignant neoplasms as myeloma, breast and prostate cancer, we hope that these patterns can help us understand why certain cells develop tolerance to stress conditions or escape antitumor drugs.