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Prof Michael Ehrmann 


Mechanism and Translational Aspects of Protein Quality Control  

Each cell hosts thousands of different proteins that vary greatly in their structures, copy number and in their chemical properties. Despite this complexity, nature has evolved efficient mechanisms of quality control to ensure that all proteins are biologically active, localised to the proper cellular compartment and present in appropriate quantity. This functional state must be maintained under normal as well as under stress conditions. The failure of quality control can influence cell growth and can cause severe diseases ranging from bacterial infections to neurodegenerative and arthritic diseases or cancer.
The focus of our current research is on the widely conserved HtrA family of serine proteases that are involved in all aspects of ATP-independent protein quality control. This work revealed that certain HtrAs can combine the antagonistic functions of chaperone and protease activities and that HtrA proteases are excellent models to study classic biochemical principles including allostery, cooperativity and activation by oligomerisation. Recently, work on human HTRA1 has revealed its involvement in cancer (as a tumor suppressor), in arthritis (by remodelling of the extracellular matrix) and in Alzheimer's disease (by degrading proteins and protein fragments that aggregate to form senile plaques). Since a number of years we are also interested in chemical biology approaches to generate tools for basic research and for drug development purposes.

Grants


BBSRC
WORD
Alzheimer's Research Trust
Lead Discovery Center
Engelhorn Foundation
DFG

Collaborations

Jon Beckwith & Dana Boyd, Harvard Medical School
http://beck2.med.harvard.edu/

Tim Clausen, IMP Vienna
http://www.imp.ac.at/research/research-groups/clausen-group/ 

Markus Kaiser, Duisburg-Essen
http://www.uni-due.de/zmb/members/kaiser/overview.html