This project is now closed

Role of intracellular transport regulators during infection of human macrophages with mycobacteria

Project supervisor – Maximiliano Gutierrez

Division of Mycobacterial Research

The key event during M. tuberculosis infection is the ability of this pathogen to survive within phagosomes in host cells. This capability is linked to the aptitude of the live pathogen to manipulate phagosome maturation. The strategy by which M. tuberculosis manipulates the cellular trafficking machinery is likely to be both multifactorial and complex. In spite of the significant progress in the last few years, a mechanistic understanding of how M. tuberculosis infection proceeds at the cellular level and how the first steps of host defenses are organized against this pathogen are still elusive.

Our group is using and developing integrated approaches that include cellular models of infection combined with mycobacteria-expressing fluorescent proteins. This project will involve the generation of tools to knockdown host cell factors that regulates intracellular transport in primary human macrophages. Afterwards, knocked-down macrophages will be used to analyze the specific role of those factors in infection. Using defined fluorescent markers of intracellular compartments and confocal microscopy/image analysis, the student will study the fate of the mycobacterial phagosomes in host cells. All these studies will be performed using M. bovis BCG and extended to M. tuberculosis later on in the project (with the appropriate supervision).

This project is suited for motivated and team-oriented students who would like to learn: 1- Cell biology of infection 2-Microscopy-based studies of host-pathogen interactions and image analysis.

References

Top of page

© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA