Project Details
Projekt
The analysis of membrane signalling networks in latex bead- and mycobacterial-phagosomes regulating actin binding and de novo assembly
Applicant
Professor Dr. Thomas Dandekar
Subject Area
Cell Biology
Term
from 2003 to 2008
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 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 Programme
Priority Programmes
Participating Persons
Professor Gareth Griffiths, Ph.D.; Privatdozent Dr. Sergei A. Kuznetsov
