Bacterial effector secretion: Function and Architecture of the Type 3 Secretion System

Objective

Bacterial pathogens secrete effector proteins to manipulate host cells during infection. In Gram-negative bacteria the conserved type 3 secretion system (T3SS) delivers effector proteins to the host cell in a spatiotemporal manner. Although major T3SS constituting components were identified the function of this macromolecular complex remains elusive which is why the transport mechanism is not understood yet.
Here, I present my research proposal of the functional and structural analysis of the T3SS with respect to the effector transport dynamics. The proposal is divided in three sections addressing the T3SS architecture, the cytosolic mechanism preceding effector molecule release and the molecular mechanisms of secretion regulation.
Research focus of the first section is on the 3-dimensional structural analysis of isolated T3SS. The proposed studies should help detecting structural features related to the effector transport. A combination of electron microscopy (EM) and mass spectrometry is proposed to analyze the structure and surface properties of the transport channel together with bound effector molecule. I am also planning localization of bound lipids as well as to detect lipid induced structural changes in the T3SS by EM. Characterization of cytosolic processes, preceding the translocation is the focus of the second section. Effector molecule targeting, insertion into the T3SS channel and the chaperone function will be studied using a combination of biochemical and biophysical techniques.Finally I propose experiments to analyze the T3SS regulation. Here, the research focus is on host signal reception and downstream posttranslational modifications inside bacteria as well as on conformational dynamics of the T3SS needle tip complex.
The overall goal of the proposed work is to understand the molecular mechanisms of the T3SS. I believe these studies will impact both the understanding of bacterial pathogenesis as well as the transmembrane transport of proteins.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

• natural sciences biological sciences microbiology bacteriology
• natural sciences biological sciences biochemistry biomolecules proteins
• natural sciences physical sciences optics microscopy electron microscopy
• natural sciences biological sciences biochemistry biomolecules lipids
• natural sciences chemical sciences analytical chemistry mass spectrometry

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

• FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

• ERC-SG-LS6 - ERC Starting Grant - Immunity and infection

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

ERC-2012-StG_20111109
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Funding Scheme

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ERC-SG - ERC Starting Grant

Host institution

Beneficiaries (2)