Louise Jawerth gets vidi for understanding pesky protein fibers

Mysterious protein fibers show up in the brain cells of people suffering from Alzheimer’s’ disease and other neurodegenerative disorders. Leiden physicist Louise Jawerth has been awarded a Vidi grant to find out how these fibers form in the first place.

‘This means I can do all the projects I wanted to do, instead of selecting just one,’ says a very happy physicist Louise Jawerth, who applied and got a Vidi grant amounting . This helps her hire a PhD and a postdoc to research the formation of amyloid fibers, found in brain cells of people suffering from neurodegenerative disorders, such as Alzheimer’s disease and ALS.

Jawerth was one of the authors of a landmark 2015 Cell paper showing that these fibers grow in the vicinity of liquid-like protein droplets, which float around in the watery solution of the cell. ‘The fibers seem to emanate from these droplets,’ explains Jawerth.

Intriguing microscopy movies that she made, show how the fibers grow outward in a star-like pattern, amid many ball-like droplets. It looks like ice crystals growing or mould threads on something left in the fridge for too long. ‘However, this happens on micrometre scales’, says Jawerth, ‘we can watch these processes using powerful microscopes.’

Fibers emanating from a droplet

Physicist’s approach

And this is exactly what she plans to do. The amyloid proteins exist in different physical phases: in a watery solution, in the denser droplets, and in fibers. To understand the formation and interactions between the different phases, calls for a physicist’s approach.

For instance, the presence of droplets seems to have a strong influence on the formation of fibres. Fibers tend to grow towards large droplets, apparently towards larger concentrations in the solution. Also, one growing fibre can split into two when encountering a droplet.

‘We find that droplets tend to adhere to phase boundaries, such as the boundary between the solution and another droplet’, says Jawerth. This tendency may help explain the dynamics of the fibre formation.

Alzheimer treatments

Eventually, understanding that may also help solve their relationship to the health of the brain. Protein fibres have been researched in connection with brain diseases for decades, but it is still not clear whether the fibres are causing the disease, or whether they are just a byproduct from it.

Research could eventually even point towards drugs or other treatments, says Jawerth. ‘but my research is very much foundational’, says Jawerth, ‘we want to understand the physics.’

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