Cells in our bodies are often threatened by errors in our own proteins. The FLOW consortium, comprising scientists from various institutions including Leiden, is poised to meticulously map out for the first time how cells control proteins, correcting or removing faulty ones. This endeavor holds promise for understanding and preventing diseases such as Alzheimer's, Parkinson's, or cystic fibrosis. The consortium receives a Gravity Grant of 23 million euros.
The scientists aim to understand precisely how the cell ensures that a protein folds correctly and how the cell then maintains a protein, from birth to death. The way a protein is folded is crucial for its functioning. Additionally, they will investigate how the cell disposes of a protein if, despite all efforts, it does fold incorrectly. If quality control fails, it can result in diseases such as Alzheimer's, Parkinson's, cystic fibrosis, and hemophilia.
'We aim to understand the cell's quality control process as thoroughly as possible,' says Anne Wentink. She is participating from the Leiden Institute of Chemistry. 'We can then use that knowledge to cure and prevent diseases.'
'We're now looking at the big picture'
For the first time in history, the scientists will create a comprehensive picture of all processes contributing to the functioning of certain proteins in the cell. These processes require a network of helper proteins, also known as chaperones. Science has been grappling with this issue for half a century, but it has always focused solely on different proteins and parts of the process. Vertegaal: 'Now we're looking at the big picture.'
A protein-network in a test tube
'Through this collaboration, we will soon be able to examine all individual decisions during a protein's lifespan,' says Wentink. 'My group will reconstruct certain branches of the chaperone network in the test tube. Personally, I will mainly investigate under which circumstances a protein folds correctly and under which circumstances it does not. The latter can lead to the clumping together of proteins, with harmful effects on health.'
Actively deploying quality control
'We hope that eventually we not only understand the quality controls of the cell, but also can influence them. This way, we can harness the cell's own defense mechanism to protect ourselves against protein-related diseases.'
The FLOW consortium
The principal investigator of the project is Ineke Braakman from Utrecht University. In total, there are 15 researchers involved from Utrecht University, Leiden University/LUMC, the University of Twente, and the UMC Groningen. From Leiden, Alfred Vertegaal (LUMC), Monique Mulder (LUMC), and Anne Wentink (LIC) are participating in the consortium.
