Christen Lab, Experimental Systems Biology

Mapping essential core functions of microbial genomes by transposon mutagenesis and next generation sequencing

by Pascal Kägi

Background

This Master/Semester project is part of our ongoing research efforts in which we employ hyper-saturated transposon mutagenesis coupled to high-throughput sequencing to investigate cellular core networks. Following this approach, we decoded the essential genome of the model organism Caulobacter crescentus with near base pair resolution (Christen et al. MSB, 2011). Surprisingly, our study revealed that a limited set of 480 genes representing only 12.4 % of the chromosome is sufficient to sustain bacterial life while the remaining 87.6 % of the genetic instructions seem to be dispensable during growth in rich media. What is the function of these dispensable genes? One hypothesis is that a large fraction might encode for alternative biosynthetic pathways, cellular organelles and traits essential to sustain bacterial life in their natural environment.

Project

The goal of this Master project is to experimentally define the entire set of genetic instructions that encodes all relevant biosynthetic pathways, metabolic networks and regulatory circuits needed to sustain bacterial life during limited nutrient availability. You will first generate a transposon mutant library and then perform growth selection on minimal media. Then you will use high-throughput DNA sequencing to map the entire library and then perform comparative bioinformatics analysis of the sequencing data to uncover the entire set of genetic instructions needed for growth under limited nutrients. This Master project offers the unique opportunity to combine experimental work with bioinformatics to acquire a sound knowledge on cutting-edge experimental systems biology approaches.

Skills: Interest in experimental systems-genetics, high-throughput DNA sequencing and bioinformatics

Start: position immediately available

Duration: 3-6 months - open to extension

Supervision and more information: Beat Christen and Matthias Christen

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