Reits E.A.J.: Protein breakdown in health and disease: the role of protein degradation in immunity and neurodegenerative disorders

While cells each synthesize millions of proteins per minute, similar amount of proteins need to be degraded by the degradation machineries. The degraded proteins include old proteins but also newly-synthesized but defective and misfolded proteins. The accumulation of misfolded proteins or fragments thereof is very hazardous for cells, leading to numerous disorders including
Huntington’s Disease.



Our group studies the role of protein clearance pathways in the cell, focusing on the ubiquitin-proteasome system and downstream peptidases like TPPII, and the several autophagy pathways. Using advanced fluorescence microscopy, we visualize these pathways in living cells, including FRET-FLIM, FRAP&FLIP and correlative microscopy, as well as the FlAsH&ReAsH staining technique and the usage of quenched protein fragments to identify involved proteases and peptidases. The equipment, techniques and expertise used for these studies is embedded in the Cellular Imaging core facility, which can be visited via the LCAM website.

Using aggregation-prone polyglutamine (polyQ) fragments as disease-related misfolded proteins, we examine which protein clearance pathways are involved in targeting misfolded proteins. We also want to know how these pathways can be improved to prevent disease initiation and slow disease progression, and modification of these cellular pathways may also improve healthy aging.