PhD Student - Laboratory of Biophysical Chemistry of Protein Complexes

ASK1 (apoptosis signal-regulating kinase 1) is a MAP kinase kinase kinase (MAP3K) that controls various responses to oxidative and endoplasmic reticulum (ER) stress and calcium influx via the p38 and JNK signaling pathways. Deregulation of ASK1 activity is involved in the development of many diseases, including neurological disorders, amyotrophic lateral sclerosis, cardiovascular disease, diabetes and cancer.

The catalytic activity of ASK1 is regulated through a complex mechanism that involves interaction with a variety of different binding partners including thioredoxin (TRX), TRAF factors and 14-3-3 proteins. Despite many years of intensive research, the molecular mechanism of ASK1 regulation remains unclear. The aim of this project is to elucidate the molecular basis of ASK1 regulation and to understand the role of ASK1 binding partners in its regulation.

For this purpose, the structure of ASK1 complexes with different binding partners will be studied using integrative structural biology methods, in particular cryo-EM, SAXS, H/D exchange coupled to MS and chemical crosslinking coupled to MS. This is a project in the field of structural biology and biophysical chemistry of proteins and is funded by grants from the research group.