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Project 7

Metabolic interactions between chlamydiae and their host cells

PhD position. Supervisors: Matthias Horn (UniVienna) and Michael Lalk (with input from Stephan Schmitz-Esser, UniVienna). Host: UniVienna. Secondment internship:to UniGreifswald

Rationale

Chlamydiae are major intracellular pathogens of humans but also occur frequently as endosymbionts of amoebae. Comparative genomics revealed that chlamydiae have adapted to an intracellular life style in Precambrian times, long before they diverged and evolved to pathogens or symbionts, respectively. For these highly adapted intracellular bacteria, metabolic interactions with their eukaryotic hosts are a key feature.

Objectives

To better understand chlamydial biology and evolution by comparative characterization of metabolic interactions with their host cells. A hallmark of all chlamydiae, both pathogens and symbionts, is their developmental cycle consisting of morphological and physiological different stages. We plan to gain a comprehensive overview of metabolic host interactions during this developmental cycle. We have shown recently that in contrast to previous assumptions, the extracellular stage of chlamydiae (the elementary body) is metabolically active. We plan to study this phenomenon and its implications in greater detail.

Key methods

We have used successfully confocal Raman microspectroscopy to differentiate the developmental stages of chlamydiae, and to demonstrate the uptake of the amino acid phenylalanine by chlamydiae from their host cells. Building on this, we will use Raman microspectroscopy and secondary ion mass spectrometry (nanoSIMS) in combination with incubation with stable isotope labeled substrates to systematically analyze intracellular metabolic interactions and extracellular metabolism predicted from genomics. These analyses will be supplemented by metabolite analyses of chlamydiae and their hosts by NMR and mass spectrometry techniques.