We are combining a wide range of techniques from genetics, biochemistry, and molecular cell biology with state-of-the-art mass-spectrometry approaches to test (and most often falsify...) our hypotheses. Often, we follow up on the results from 'failed' experiments. As a consequence, we end up investigating a wide range of biological processes.
We have recently discovered that the glycoprotein a-dystroglycan
contains ribitolphosphate groups, unusual sugar derivatives
previously thought to exist only in bacteria.
Defects in the the incorporation of ribitolphosphate lead to
neuromuscular disease. Currently, we are trying to understand the
missing steps in biogenesis of ribitolphosphate
Metabolism of 'weird' lipids
Textbook biochemistry describes that most fatty acids are synthesized in the
cytoplasm and contain a linear chain of carbon atoms.
While this is correct, it does not represent the entire spectrum of fatty acid synthesis,
since some fatty acids contain branches in their carbon backbone.
Furthermore, an independent fatty acid synthesis system exists in mitochondria.
We only know little about how these ‘unusual’ pathways contribute to physiology and disease.
We want to change this!
Metabolite repair
Many enzymes do not only act on their physiological substrate
but also on substrates that are structurally related.
This leads to the production of side-products that can be toxic to cells.
To prevent this toxicity, dedicated enzymes exist that eliminate these side-products
or convert them into useful metabolites.
In our work, we try to understand the role of these
metabolite repair enzymes in human metabolism.
Neurodegenerative diseases
Cells are continuously exposed to potentially dangerous compounds.
Progressive accumulation of damage is suspected to contribute to
neurodegenerative diseases and aging, but the molecular identity
of the damage remains largely unknown.
We have recently discovered that PARK7, an enzyme mutated in
hereditary Parkinson's disease, prevents damage of
proteins and metabolites caused by a metabolite of glycolysis.
Currently, we are trying to reveal the connection between
this type of damage and neurodegeneration.
We hope that a better understanding of this link
will eventually allow for the development of therapeutic approaches.
Cancer metabolism
Cancer cells need to undergo metabolic adaptations.
We are trying to find out whether some of
these adaptations might lead to vulnerabilities
that can be exploited therapeutically.
Inherited errors of metabolism
Mutations in genes coding for enzymes can lead to devastating diseases.
Symptomatic and causal therapies for these diseases require
a thorough understanding of the role of the affect
enzymes in human metabolism.
miRNAs are short regulatory RNAs consisting of 18 - 24 nucleotides.
They interact with reverse complementary sequences in the 3' untranslated region
of protein-coding transcripts thereby reducing protein production.
We are investigating how miRNAs and proteins
collaborate to exert a common function.