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Are you looking for a PhD project at the interface of microbiology, genetics and biochemistry and do you like bioinformatics? As a PhD candidate, you will aim to discover the function of enzymes and metabolites in Mycobacterium tuberculosis using genetic screens and untargeted metabolomics. This way, we can help develop tuberculosis drugs with new mechanisms which we urgently need.
Tuberculosis (TB) has plagued humans for thousands of years and remains one of the leading causes of death worldwide today. Tuberculosis is caused by Mycobacterium tuberculosis (Mtb), a bacterial pathogen that infects about a quarter of the world's population. Although the frontline drugs are effective, drug resistance is emerging as a major threat to global TB control. TB drugs with new mechanisms of action are thus urgently needed. One rich and untapped source of new drug targets is the sizeable part of the Mtb genome that is uncharacterised. A large number of these genes are expected to encode enzymes, which generally represent druggable targets. However, without a known function, these potential drug targets are beyond reach for target‐based drug discovery. In this NWO-funded project, you will apply a new type of functional genomics screen that aims to annotate genes by globally mapping their interaction with Mtb metabolites. Building on the experience in our group, you will combine metabolite fractionation with state-of-the-art untargeted LC-MS metabolomics and CRISPRi gene vulnerability screens. After extensive computational analysis, hits from these screens will be validated using a suite of experimental techniques (e.g. NMR, heterologous protein expression, protein purification, and metabolic profiling of Mtb mutants). Opportunities for collaboration exist within the Radboud Institute for Biological and Environmental Sciences (RIBES), the Institute for Molecules and Materials (IMM) and the department of Medical Microbiology of the Radboud university medical center.
You will communicate your results at national and international meetings and in scientific journals. As a member of the Microbiology cluster, you will be expected to contribute 10% of your working time to teaching in the BSc Biology programme or the MSc Microbiology specialisation track. All PhD candidates at RIBES participate in the RIBES Graduate School and have the opportunity to receive training, develop their personal and professional skills, and prepare for their future career.
Fixed-term contract: you will be employed for an initial period of 18 months, after which your performance will be evaluated. If the evaluation is positive, the contract will be extended by 2.5 years (4 year contract).
This project will be carried out in the Functional Metabolomics group of Robert Jansen, which uses untargeted metabolomics to discover the function of uncharacterised enzymes and metabolites in microbes. The group is embedded in the Microbiology Cluster of the Radboud Institute for Biological and Environmental Sciences (RIBES).
The Microbiology Cluster comprises an enthusiastic and devoted team of researchers who closely collaborate in a flat organisational structure. Harmonious and productive collaboration and synergy are key to our success. The Cluster has state-of-the-art equipment for sequencing and data analysis, light and electron microscopy, metabolomics, an MLII lab, a large bioreactor facility as well as infrastructure for anaerobic microbiology, and facilities for biochemical, molecular and physiological work. Our mission is to conduct research at the forefront of microbial ecology and physiology and biogeochemistry with the main aim of understanding the diversity of microorganisms responsible for the biogeochemical cycling of nitrogen and carbon, and host-microbe interactions. We have expertise in microbial metabolomics, microbial cell biology and biochemistry, environmental microbiology, microbial biotechnology, geomicrobiology and biogeochemistry, microbial ecophysiology and microbial meta-omics.
The Microbiology cluster is part of the Radboud Institute for Biological and Environmental Sciences (RIBES). RIBES aims to perform world-leading research in order to understand the response of the natural environment to human impact. Research at RIBES encompasses three major groups of organisms (microorganisms, plants and animals) and spans nearly all levels of biological organisation. The institute is organised in three clusters: Ecology and Physiology, Environmental Science, and Microbiology.
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