Proper cell function is dependent on the proteins and other molecules in the cell being correctly folded and organised. One way cells do this is by phase separation, a physical phenomenon similar to the demixing of oil and vinegar in a vinaigrette. Phase separation is crucial for many aspects of gene regulation, such as organising RNA-protein complexes and epigenetics, as well as genome organisation and genome stability. Dysregulation of phase separation or failure to remove misfolded and damaged proteins can result in the formation of insoluble protein aggregates that contribute to neurodegenerative disease.
Researchers at IMB work on resolving the impact of protein order and disorder in relation to all these topics. A Germany-wide initiative on this subject (SPP 2191 on “Molecular Mechanisms of Functional Phase Separation”) is coordinated by one of IMB’s researchers (Prof. Edward Lemke). Specific examples of this research at IMB include:
- Molecular mechanisms of neurodegenerative diseases
- Nuclear pore function
- Ribonucleoprotein complex transport and organisation through condensates
- Spatial organisation of DNA repair
- Computer simulation of interactions between disordered proteins
- Protein homeostasis and turnover