Polypharmacological" design of inhibitors

The dual-specificity tyrosine phosphorylation-regulated kinase family (DYRKs) has recently emerged as new therapeutic targets for different kinds of cancer and neurodegenerative diseases. In the latest studies it was shown that DYRKs plays a key role in neurodegenerative diseases, cancer cell survival, and its inhibition induces apoptosis of cancer cells.

This master's thesis project is about the biophysical characterization of DYRK1A and its comparison to co-targets identified in polypharmacological approaches. Expression and purification protocols for large-scale protein production of DYRK1A are established, as well as crystallization protocols for DYRK1A.

The project includes:

Expression and purification of DYRK1A

Expression and purification of co-target(s)

Crystallization of co-target(s)

Characterization of kinase inhibitors (activity assays, ICT, thermophoresis, etc….)

Cocrystallization of DYRK1A with inhibitors.