Rebooting brain cell’s built-in cleaning systems

Lead Investigator: Dr Daniel Maddison  

Institution: University of Cambridge

Grant type: Postdoctoral Fellowship

Start date: March 2026

Duration: 36 months

Amount: £252,480.99

Summary sentence:

Dr Maddison’s research will investigate the cleaning system that clears away damaged proteins, like the early tau build-up in Alzheimer’s disease, and look for ways to help this process work faster.

Short description (100 words):

In Alzheimer’s disease, two proteins called amyloid and tau build up and form plaques and tangles, which causes brain cells to die. Normally, our cells have built in cleaning systems that spot damaged proteins and repair or remove them. But this system slows down with age, meaning proteins can build up.

Dr Maddison aims to follow this cleaning system in real-time in cells in a dish using powerful microscopes. This will allow him to pinpoint exactly which components make up the cleaning system and which one specifically acts as the on switch. Dr Maddison will then look for potential drugs that could reboot ageing cleaning systems.

Long description (250 words):

In Alzheimer’s disease, two proteins called amyloid and tau build up and form plaques and tangles, which causes brain cells to die. Normally, our cells have built in cleaning systems that spot damaged proteins and repair or remove them. But this system slows down with age, meaning proteins can build up.

Using lab-grown brain cells and fluorescent tags, Dr Maddison will follow the cleaning system in real-time using powerful microscopes. He aims to understand what activates the cleaning system, how fast damaged tau proteins are cleared and when the cleaning system becomes overwhelmed.

To better understand how the cleaning system works, Dr Maddison will break down the cells to pinpoint the components that make up the cleaning system. By selectively preventing cells from making these components, he can watch how the cleaning system changes when key parts are missing.

With this new knowledge, Dr Maddison will search for potential drugs that interact with these newly identified cleaning system components to try and reboot ageing cleaning systems. This could stop the build-up of tau before it can damage brain cells, slow Alzheimer’s disease and prevent the symptoms of dementia.