Proteins are crucial for cellular and human life; they need to fold into 3D structures for functionality. Human cells have a quality control network to ensure the proper formation of their 20,000 proteins, critical for adapting to diverse conditions and resisting stress. However, this system has limitations, leading to diseases when malfunctioning. In Loss-of-Function (LoF) diseases like cystic fibrosis, a specific protein misfolds, leading to dysfunction through aggregation or breakdown. On the other hand in Gain-of-Toxicity (GoT) conditions such as Parkinson's, proteins form toxic aggregates instead of their correct functional structures. Due to our limited understanding of the molecular processes involved in protein biogenesis, we hold back the development of treatments for most protein-related diseases.
Project FLOW
In project FLOW (Ferrying proteins across Landscapes, Opening pathways to Wholesomeness), the consortium aims to gain better understanding of the protein quality-control process and methodologies required to address the complex cellular protein quality-control network in its entirety. Unique in FLOW is that every partner is committed to study both LoF and GoT proteins, offering an unique view of protein biogenesis. Besides experiments in the lab, the researchers will use advanced techniques to fully study this research problem and as a whole - from living cells to intramolecular level. This helps them understand the diseases better.
New treatments
The research project significantly impacts the understanding and treatment of protein-related diseases, initially Parkinson and cystic fibrosis, as FLOW will identify promising drug targets and their modes of action in the QC network. Evan Spruijt, researcher at IMM, will specifically look at the role of biomolecular condensates as protein quality control compartments in the QC network. The FLOW project will further enable the efficient cellular manufacturing of a broad spectrum of engineered proteins for medical and biotechnological applications.
Gravitation Programme
The funding is part of the NWO Gravitation Programme, an initiative form the Dutch government that supports outstanding scientific research. Initially, research projects get half their funds, with the chance to gain the rest after a five-year review. For FLOW, it means a potential extra 11 million euros.
