PhD defence: FibrilPaints to detect, study and modulate amyloid fibrils

PLEASE NOTE: The candidate gives a layman's talk, therefore the livestream will start fifteen minutes earlier.

Brain diseases such as Alzheimer's, Parkinson's, and Huntington's have something in common: nerve cells in the brain slowly die, causing people to lose their memory, movement, or independence. Although these diseases seem very different, they share a striking feature. Certain proteins, which normally do useful work inside our cells, fold the wrong way and stick together into long, thread-like clumps: fibrils. These clumps build up and damage the brain.

This thesis introduces FibrilPaints: small molecules that attach specifically to these protein clumps, almost like marking them with a highlighter. Because they bind so precisely, FibrilPaints can be used as a toolset for different purposes.

One application is the FibrilRuler Test, which uses FibrilPaints to measure how long the clumps are. The FibrilRuler Test could one day help with diagnosis, for example in Parkinson's, where good tests are still lacking. Because it measures the length of the clumps, it may reveal how far the disease has progressed.

Another is targeted breakdown: a FibrilPaint can be given an extra "label" that tells the cell's own cleanup system to dispose of the clump. For some proteins this works well; for others it turns out to be harder, showing that not all clumps behave the same way.

Together, these tools offer a new way to detect, study, and perhaps one day treat brain diseases. This is timely, as targeting these protein clumps is once again proving to be a promising route towards new treatments.