Detailseite
Projekt
Die Analyse von Membran-Signalnetzwerken bezüglich Bindung und de novo Assemblierung von Aktin in latex bead - und mykobakteriellen Phagosomen
Antragsteller
Professor Dr. Thomas Dandekar
Fachliche Zuordnung
Zellbiologie
Förderung
Förderung von 2003 bis 2008
Projektkennung
Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 5407324
Two in vitro assays have been developed to analyse how a defined cytoplasmic membrane surface, latex bead phagosomes (LBP) from macrophages (A) assembles actin de novo and (B) binds to F-actin. A large network of proteins and lipids has been identified that regulates the assembly process. The phagosomes of non-pathogenic mycobacteria were found to assemble actin similarly to the LBP but those containing the pathogens M.tuberculosis or M.avium are known to be strongly inhibited in this process, in fusion with lysosomes and in acidification. Lipids were identified that, when added to infected cells could switch on, not only actin assembly by pathogenic mycobacterial phagosomes but also phagosomal maturation in general, leading to pathogen killing. A biocomputing approach, elementary mode analysis is being applied to identify the flux modes of metabolites through the network in the phagosomal membrane, leading to many predictions which could be experimentally verified. Our goal is to combine theory and experiments to provide a holistic description of how membrane signalling networks regulate two defined membrane functions, actin assembly and binding.
DFG-Verfahren
Schwerpunktprogramme
Beteiligte Personen
Professor Gareth Griffiths, Ph.D.; Privatdozent Dr. Sergei A. Kuznetsov
