Creating in vitro assembled protein nano-fibrils that mimic polymorphous disease-relevant amyloid structures formed in vivo

Amyloid fibrils grown in a test tube do not match the shapes of those found in human tissue, so researchers are building a new imaging technique to reconstruct their three-dimensional structures one fibril at a time. This matters because amyloid fibrils—the protein aggregates linked to diseases such as Alzheimer’s and Parkinson’s—are highly polymorphic: identical protein sequences can assemble into a continuous range of different filament shapes. Current lab-grown fibrils generally fail to reproduce the structures seen in patient tissues, making it difficult to study how specific fibril shapes relate to disease progression or drug response. The project will combine atomic force microscopy with biophysics and structural bioinformatics to create in vitro systems that generate disease-relevant amyloid structures. If successful, the technology could enable researchers to produce fibrils that faithfully mimic those found in patients, improving the relevance of laboratory models for neurodegenerative diseases. This is primarily fundamental science—it builds a new tool for structural biology rather than delivering an immediate clinical application. But similar advances in protein structure determination have historically opened doors to drug design and diagnostic development that were not predictable at the outset.