Diagramme of a type VII secretion system, as will be investigated in the CombaT7 project. (Picture: Marlovits lab / CSSB)
Scientist Thomas Marlovits (DESY/CSSB/UKE) together with three other researchers, Edith Houben from Vrije Universiteit in Amsterdam, Tracy Palmer from Newcastle University and John McKinney, PhD, EPFL Lausanne received an ERC Synergy grant for their project ‘CombaT7’, for which they will receive funding of 10.8 millionn euro to be used over a period of six years. The project aims to provide a deep mechanistic understanding of the diverse roles of mycobacterial T7SSs and to develop insights into how exploiting these systems may help combat infections.
Bacteria interact with their environment via specialised secretion systems that deliver proteins outside of the cell. The type VII secretion system (T7SS), is widespread in Gram-positive bacteria and actinobacteria, including the important human pathogen Mycobacterium tuberculosis. While the mechanism of secretion via T7SSs is not well understood, the recently determined atomic structure of the T7SS from M. tuberculosis (Bunduc et al Nature 2021) provides a three-dimensional blueprint for further investigation. Moreover, preliminary data suggests that their roles and substrates are more diverse than initially thought. The project aims to structurally define the full trans-envelope T7SS, study the mechanism of transport, expand the set of T7SS substrates and visualise the role of T7SS in bacterial warfare and host-pathogen interactions.
The project scientists are leading experts in microbiology, structural biology, cell biology, and biophysics. Over the course of the project, they will use several methods including correlate atomic force microscopy, cryo-electron microscopy, proteomics, and bioinformatics analysis as well as innovative lung-on-a-chip infection models and time-lapse microscopy to develop an in-depth understanding of mycobacterial T7SSs.
Together, the project team will be able to address multiple important unanswered questions about the physiology and virulence mechanisms of several relevant mycobacterial pathogens. “This project will not only further our understanding of T7SS and but also reveal novel ways to exploit the T7SS system,” notes Marlovits “I am looking forward to working on this project with my collaborators over the next couple of years.”
ERC Synergy Grants are awarded by the European Research Council to groups of two to four excellent researchers who work together to bring different skills and resources to tackle ambitious research problems. This is the second ERC Synergy Grant awarded to a CSSB scientist.
(from DESY News)
