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Dynamische Protein-Dimerisierung und Membran-Translokation

English title Dynamic Protein Dimerization and Membrane Translocation
Applicant Wymann Matthias
Number 126508
Funding scheme Project funding (Div. I-III)
Research institution Institut für Biochemie und Genetik Universität Basel
Institution of higher education University of Basel - BS
Main discipline Organic Chemistry
Start/End 01.01.2010 - 31.12.2011
Approved amount 227'421.90
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All Disciplines (3)

Discipline
Organic Chemistry
Cellular Biology, Cytology
Biochemistry

Keywords (10)

Chemistry; Protein/protein interactions; Protein/membrane interactions; Phosphoinositide kinases; Molecular tools; Chemical Biology; synthetic chemistry; signal transduction; cancer; inflammation

Lay Summary (English)

Lead
Lay summary
Protein/protein and protein/membrane interactions play a major role in the activation of cellular signaling cascades in physiology and disease. Recently, receptor activation and signal transduction in restricted membrane micro-domains has gained importance, but tools to validate these processes are scarce.Here we propose to produce chemical protein translocators and dimerizers, that will be used to explore sub-membrane domain signaling of lipid modifying enzymes like phosphoinositide kinases and phosphatases. In particular phosphoinositide 3-kinases (PI3Ks) play a major role in the control of cellular growth, proliferation, migration, energy metabolism and more, and thus modulate progression of cancer and inflammation (Vivanco and Sawyers, 2002; Cantley, 2002; Wymann et al., 2003; Wymann and Marone, 2005). Involving interdisciplinary approaches we aim to to develop novel tools to monitor and influence PI3K activities in space and time.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Associated projects

Number Title Start Funding scheme
138302 Chemische Induktion der intrazellulären Signalübertragung 01.01.2012 Project funding (Div. I-III)
139260 Rapid, multi-mode, live imaging and photo-manipulation of protein and activation dynamics at the plasma membrane 01.01.2012 R'EQUIP
133860 High Content and High Throughput Microscopy to Decipher Signaling Networks 01.12.2010 R'EQUIP
143699 Kovalente Tag Chemie - Intrazelluläre Kontrolle von Receptoren und Signalen 01.01.2013 Project funding (Div. I-III)
138302 Chemische Induktion der intrazellulären Signalübertragung 01.01.2012 Project funding (Div. I-III)

Abstract

Protein/Protein und Protein/Membran-Interaktionen spielen eine zentrale Rolle bei der Aktivierung von Signalübertragungskaskaden in physiologischen und pathologischen Prozessen. Rezeptoren und Signale aus speziellen zellulären Membran-Mikrodomänen haben an Bedeutung gewonnen, es gibt jedoch sehr wenig molekulare Werkzeuge, um solche Prozesse zu validieren. Das hier vorgestellte Projekt zur Herstellung von chemisch reaktiven Substanzen zur Translokation und Dimerisation von Proteinen soll es ermöglichen, lokalisierte Signale von z.B. Phosphoinositidkinasen und Phosphatasen zu studieren.
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