New stress-response metabolites in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis (TB), a disease that kills ~1.5 million people each year. The backbone of the current treatment is formed by drugs from the 50s and 60s of the last century. Not surprisingly, drug-resistance is widespread, leading to an urgent need for new drug targets. We aim to discover new Mtb metabolites and their biosynthetic genes and, thereby, identify new potential drug targets. To discover new enzymes and metabolic pathways involved in pathogenesis, we use a bottom-up approach by performing untargeted metabolic profiling on Mtb exposed to various stresses imposed by our immune system.

Mapping the effects of metabolite supplementation on gene essentiality in Mycobacterium tuberculosis

Metabolite supplementation to a cell culture affects the essentiality of genes and thereby allows mapping an unchartered territory of gene‐metabolite interactions. In this project we aim to discover the function of Mycobacterium tuberculosis genes by combining CRISPRi technology with untargeted metabolomics. 

The metabolic dark matter of anammox bacteria

Anaerobic ammonium-oxidizing (anammox) bacteria are a relatively new class of bacteria that anaerobically oxidize ammonium to N 2, a reaction that accounts for a considerable portion of the atmospheric N 2. The unique chemistry of this reaction – which involves highly toxic intermediates – is performed in a dedicated cell structure called the anammoxosome. Although the key enzymes in the anammox process are identified, the anammoxosome contains many proteins of unknown function and its metabolome remains unexplored. A deeper understanding of the anammox process will help to improve wastewater treatment and to understand how organisms cope with toxic metabolites.