Project Details
Projekt
Protein networks involved in biogenesis of the Salmonella proliferative niche
Applicant
Professor Dr. Ivan Dikic
Subject Area
Cell Biology
Biochemistry
Immunology
Biochemistry
Immunology
Term
from 2014 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 261251403
The gram-negative bacterium Salmonella enterica has provided many insights into the infection process of epithelial cells and how intracellular pathogens can manipulate the host endo-membrane system and evade internal defence strategies. We are interested to molecularly characterise membrane dynamics during Salmonella infection, in particular how Salmonella manipulate and recruit membrane sources required for the maintenance and growth of Salmonella containing vacuoles (SCVs). Under non-infected conditions, these pathways are regulated by small Rab GTPases, their effector proteins and membrane fusion machineries such as the homeotypic protein sorting (HOPS) complex. By using mass spectrometry, we have identified the adaptor protein Plekhm1 (Pleckstrin homology domain containing family member 1) as an effector of active Rab7 (Rab7.GTP) that also binds to the HOPS complex. In this proposal we will test whether key Salmonella effector proteins function as regulators of the Salmonella containing membrane compartments and how they may manipulate the endosomal network. Moreover, we will focus on cellular host proteins that interact with bacterial effector proteins and other elements of the lysosomal membrane fusion machinery that may regulate this process through direct interaction or by the modification of the composition of the lysosomal membrane itself. Overall, this proposal addresses key questions on which pathogen- and host-derived compounds contribute to biogenesis of Salmonella containing compartments.
DFG Programme
Priority Programmes
International Connection
Switzerland, United Kingdom
Participating Persons
Professor Dr. Dirk Bumann; Professor Dr. Achilleas Frangakis; Professor Dr. David Holden
