Different environmental cues such as stress, nutrients or drugs, trigger rapid adaptive responses that allow to maintain cellular homeostasis. One of the fastest cellular responses to the environment is the binding of small molecules to proteins. These molecular interactions produce allosteric effects, which means that they trigger a variation of protein activity as a consequence of a structural conformational changes that occurs instantly. Allosteric interactions are thus essential for life and can modulate both the metabolic status of the cells and gene expression.
We study how cells adapt to different metabolite compounds at the molecular level, focusing on the regulation of the balance between cellular proliferation and terminal differentiation in stem cells. Metabolite levels can control both the inherent proliferative properties of stem cells in normal conditions but also their uncontrolled proliferation, which may lead to diseases like cancer.
In cancer diseases leukaemia the balance between cellular proliferation and differentiation is impaired. Our team is interested in understanding how this happens at the molecular level. We will use multiple system biology approaches with a particular focus on novel proteomics methods, metabolomics and genomics to study:
- The principles and pervasiveness of metabolite regulation of chromatin.
- How metabolites control stem cells fate in leukaemia.
- How to efficiently modulate the chromatin-metabolite network with drugs.
To tackle these questions we need advanced bioinformatics and a structural-system biology prospective. We will integrate these different levels of gene regulation into predictive models that elucidate their function in collaboration with other research groups at the MDC and with the Berlin institute of medical system biology.