Sauer Lab: Master thesis "Investigating protein-metabolite interactions in E. coli"

In this project, we aim at inferring functional protein-metabolite interactions in the bacterium Escherichia coli from dynamic metabolomics data.

by Dimitrios Christodoulou

Protein-metabolite interactions are involved in the regulation of many cellular processes, such as metabolism and signaling, and are particularly important to achieve fast adaptation to new environments. Previous research has already identified many proteins and metabolites that are hypothesized to take part in protein-metabolite interactions, but current methods do not allow for systematic testing of all candidates.

In this project, we aim at inferring functional protein-metabolite interactions in the bacterium Escherichia coli from dynamic metabolomics data. Therefore, we have developed an approach to probe hypothesized signal-metabolites in vivo and to infer potential protein targets based on dynamic metabolite data. In this project, you will selectively perturb metabolite concentrations inside growing E. coli cells and characterize the dynamic metabolic response using state-of-the-art metabolomics techniques. Specifically, you will use an already established set of compounds to increase the concentration of known and hypothesized signal-metabolites inside the cell, while dynamically sampling intracellular metabolites. Following sample generation, untargeted mass spectrometry will be used to profile the dynamic response of ~300 metabolites. The resulting dataset will be processed and you will have time to explore it using state-of-the art computational analysis tools. Based on computational analysis of the temporal metabolite profiles, you will develop hypotheses about potential allosterically regulated enzymes. To finalize the project, you will experimentally test the newly predicted protein-metabolite interactions using enzyme assays.

This project is designed for a motivated student with an analytical mindset, ideally with some background in biology/biochemistry and coding (Matlab). If you are interested and/or have further questions, just send me an email or drop by for a coffee in room D59.
Maren ()

 

In this project, you will acquire the following techniques/skills:

-          Planning of large-scale experiments

-          Culturing E. coli cells

-          Extraction of intracellular metabolites

-          Untargeted mass spectrometry (measurements & data processing)

-          Data analysis using Matlab

-          Hypothesis generation from large datasets

-          Enzyme assays

-          …

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