Medicinal Chemistry Research
Jagtvej 162, 2100 København Ø
My research interest focuses on the scientific question:
“How does post-translational protein modification affect protein activity and folding, and how does this contribute to infection and disease?”.
One of the most commonly known causative agents of unregulated post-translational protein modification is oxidative stress. The corresponding cellular counter measure to reinstate redox homeostasis and to maintain the required protein folding conditions is the deployment of antioxidant systems and molecular chaperones.
This highly dynamic interplay of protein folding and oxidative stress is prominently evident in the so-called protein folding diseases (e.g. Parkinson’s disease, Alzheimer’s disease). Here, protein folding and redox misregulation is hypothesized to play a crucial role but the causal connection between both oxidative stress and protein unfolding is still under debate.
Oxidative stress is a rather broad term but involves a large variety of different types of (oxidative) post-translational protein modification. It is not fully understood what types of modification occur, how these are recognized, and how these modifications determine and influence cellular metabolism and proteomics.
It is very important to understand interference and alteration of the cellular proteome as this is linked to various clinically relevant developments, such as ageing, neurodegenerative disorders, and cancer.
New types of post-translational protein modifications
The use of small synthetic molecules in conjunction with chemical biology and biophysical methods allows studying the role of specific post-translational protein modifications that putatively contribute to the pathogenesis of neurodegenerative disorders. Current efforts target protein modification linked to Parkinson's disease.
Interplay of oxidative stress and chaperones in neurodegenerative disorders
The dynamic interplay between oxidative stress and protein folding is evident in neurodegenerative disorders. The combination of chemical and synthetic biology with molecular cell biology and protein biochemistry provides fascinating insights into this interactive protein-protein interaction network. Recent projects address pathways of oxidative protein folding that are implicated in Alzheimer’s disease.
Development of peptide-based inhibitors to modulate cellular protein folding and aggregation pathways
Another strategy to decipher the complex of protein folding and disease is to develop and apply specific inhibitors targeting pathways that are associated with protein processing, folding, and aggregation. To do so we apply peptide chemistry to develop inhibitors of specific protein-protein interactions. This provides us with either biological tools to further study biological activity but also with potential lead compounds for further drug development targeting macromolecular complexes in a variety of clinically relevant pathologies.
The main techniques revolve around the large field of protein biochemistry and protein biophysics. In addition, standard cell culture and classic molecular biology are frequently used along with peptide chemistry and small molecule synthesis. Finally, computational biology and bioinformatics are crucial methods for study and analysis.
Are you interested?
We actually need some helping hands and are offering the following research projects to interested students:
- The role of protein modification in the pathology of Parkinson's disease
- Deceiphering the interaction of protein folding and redox-regulation in Alzheimer's disease
- Regulating the activity of protein folding machineries in Parkinson's disease
International/exchange/visiting/Erasmus students are welcome!
We are also very interested in students, graduates, PhDs who would like to purse long-term projects.
Please contact us by email.