Research

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.

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

Immunotherapy has become standard of care for many people with advanced stage lung cancer and greatly improved life expectancy and quality of life. Unfortunately, only about half of people with metastasized non-small cell lung cancer benefit from this expensive treatment and predicting response is currently not possible. In this project, which is tied to the clinical DEDICATION study, we aim to assess the predictive value of microbiome-derived short-chain fatty acids for treatment response, and identify novel microbial biomarkers.

The NWO-XL project CLIMET studies how climate-driven changes in dissolved organic matter and dust impact microbial production and consumption of the greenhouse gas methane in Arctic lakes. The project aims to better understand methane emissions and climate feedbacks. Our specific goal is to link the presence of microbes (metagenomics) and metabolites (metabolomics) in Greenland lakes to physical factors and methane emissions. 

Lake Grevelingen is a seasonally stratified marine lake that suffers from long periods of hypoxia. In this collaborative project with professor Caroline Slomp (biogeochemistry), we aim to explore the metabolome of the lake water and link known and unknown metabolites to microbial and biogeochemical processes. 

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.