Cel "Most drugs act via cell surface receptors. Some receptors signal to ion channels, while others regulate 2nd messengers, most importantly cAMP. Ion channels can be resolved at the single channel level using patch clamp analysis; they switch between discrete ""on"" and ""off"" states. In contrast, current techniques to analyze cAMP-signals are quite global and generally require destruction of the sample. Therefore, the activation mechanisms and switching behaviour of receptors signalling to cAMP are largely unknown. This project postulates minimal quantal cAMP-signals that are triggered by individual receptors. We aim to discover these quantal cAMP-signals, to characterize their temporal and spatial patterns, and to determine factors that influence them. To do so, we will develop a microscopic technology to image cAMP-signals with high sensitivity and resolution. We have already developed a first generation of cAMP-sensors that can be expressed in cells and respond to cAMP with a change in fluorescence resonance energy transfer (FRET). We will carry this technology to the sensitivity required for the postulated quantal cAMP-signals and - develop new FRET-sensors for cAMP with much greater brightness, amplitude and sensitivity, - build a specially designed total internal reflection fluorescence (TIRF) microscope to image the sub-membrane region of intact cells, - apply the technology to systems of increasing biological complexity: (a) isolated thyroid cells, where cAMP-signals can be compartmentalized, (b) intact thyroid follicles, where cAMP-signals can be triggered from various cellular sites, and (c) individual neurons in Drosophila brain, which are involved in a defined learning process. We believe that the ability to analyze 2nd messenger responses from individual receptors will open the way to a molecular understanding of receptor function and cAMP-signalling and provide a widely applicable technology and a mechanistic basis for receptor-directed drug development." Dziedzina nauki medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesphysical sciencesopticsmicroscopy Słowa kluczowe FLUORESCENCE G-PROTEINS RECEPTORS SIGNAL TRANSDUCTION SINGLE MOLECULE DETECTION cAMP camp fluorescence g-proteins receptors signal transduction single molecule detection Program(-y) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Zaproszenie do składania wniosków ERC-2008-AdG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-AG - ERC Advanced Grant Instytucja przyjmująca JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG Wkład UE € 2 493 357,60 Adres SANDERRING 2 97070 Wuerzburg Niemcy Zobacz na mapie Region Bayern Unterfranken Würzburg, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Christian Gloggengiesser (Mr.) Kierownik naukowy Martin Lohse (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG Niemcy Wkład UE € 2 493 357,60 Adres SANDERRING 2 97070 Wuerzburg Zobacz na mapie Region Bayern Unterfranken Würzburg, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Christian Gloggengiesser (Mr.) Kierownik naukowy Martin Lohse (Prof.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
