University of Bremen: New Perspectives on Huntington’s Disease | India Education | Latest Education News | World Education News
Huntington’s disease is an inherited disease that leads to cognitive and motor impairment and death. Scientists from the University of Bremen and international partners have elucidated the mechanism by which the mutated huntingtin protein can be controlled.
“We have elucidated a mechanism by which so-called endogenous protein folding helpers control the mutant huntingtin protein,” says project leader and Professor Janine Kirstein from the University of Bremen. Protein folding facilitators allow proteins to assume and maintain their proper structure to perform their multiple functions. The researchers already knew about three of the protein folding helpers. But what they didn’t know yet: How exactly does the binding with mutated huntingtin look like a protein? Which of the three folding helpers does the mutated protein recognize and how does binding work? “We have now been able to identify it thanks to the crosslinking mass spectrometry method”, explains the biochemist. Protein interactions can be precisely determined with the method. However, there was still a long way to go to understand the connection. “Only through modeling have we been able to better understand the interplay between protein folding aids and mutated huntingtin.”
The success of research thanks to practiced interdisciplinarity
The success of these new discoveries is seen in interdisciplinarity: “The fact that we were able to obtain our results with such precision is mainly due to the very good cooperation between the biology/chemistry and production engineering departments of the ‘University of Bremen’, explains Janine Kirstein We need researchers for our project who can support us in our experimental work in the laboratory with computer-aided models. Janine Kirstein’s doctoral student, Yasmin Richter, found the necessary engineering expertise in her former fellow student from the master’s program in biochemistry and molecular biology, Isabell Grothaus. Isabell Grothaus is doing her doctorate in the group of Dr Susan Koppen and Professor Lucio Colombi Ciacchi. This is how the two young scientists created cooperation between the two departments. “The engineers simulated for us the binding between the protein folding aids and the mutated huntingtin protein on the computer, and we were then able to experimentally validate the models in our laboratory with purified proteins and in cell cultures”, explains Janine Kirstein .
Another hurdle was the previously unknown structure of the mutated huntingtin protein. Cooperation partners Martin Kulke and Josh Vermaas from Michigan State University in the USA were able to help here, postulating a structure with which modeling could be done on the computer. Another important cooperation partner was Fan Liu for mass spectrometry experiments at the Leibniz Research Institute for Molecular Pharmacology in Berlin, where Janine Kirstein was research group leader until 2019 before being appointed to the University of Bremen.
Rely on research results
“Thanks to this work, we managed to understand the mechanism by which a protein folding assistant selectively recognizes a disease-associated mutated protein and renders it harmless. This alone is not enough for therapeutic use,” says Janine Kirstein. “But you can build on these findings and develop strategies to specifically induce or stabilize these endogenous folding helpers to suppress mutant huntingtin toxicity.”