Dr. Mathieu Bourdenx, Group Leader at the UK Dementia Research Institute (UK DRI) at UCL, will co-lead a £3.8 million research project supported by a Wellcome Discovery Award. The project will investigate cellular mechanisms that may help protect neurons from damage caused by cellular stress and ageing.

The research builds on a recent discovery by Professor Jernej Ule’s group at King’s College London: a cellular mechanism known as interstasis. This mechanism helps cells regulate proteins that naturally gather into small, liquid-like structures called condensates. These condensates play an important role in organising proteins and RNA molecules within cells. However, they must be carefully controlled, as they can sometimes develop into harmful protein clumps.

A new collaboration between researchers at the UK Dementia Research Institute at King’s College London and UCL will explore how interstasis may prevent the formation of toxic protein aggregates. The researchers will also examine whether this mechanism can help protect neurons from cellular stress and support healthy brain ageing.

Professor Ule will work alongside Dr. Bourdenx, who will lead efforts to screen small molecules, including proteins and RNA, to better understand how they interact and influence cellular mechanisms such as interstasis.

In healthy cells, proteins carry out essential functions that support normal cellular activity, while RNA delivers the genetic instructions required to produce new proteins from DNA. In several age-related conditions, including Alzheimer’s disease and motor neuron disease, certain proteins can accumulate and form toxic clumps inside cells. These aggregates can interfere with normal cellular processes and contribute to neurodegeneration.

Interstasis enables cells to detect the buildup of proteins within condensates and regulate the production of additional proteins. It does this by allowing condensate-forming proteins to capture their own messenger RNAs (mRNAs), which contain the instructions for producing those proteins. By trapping these mRNAs, the mechanism slows further protein production and helps maintain cellular balance.

The new funding will allow researchers to investigate how interstasis regulates neuronal condensates and whether it can reduce the formation of toxic protein clumps. The team will also study how this protective mechanism may be affected when neurons experience stress related to ageing or environmental factors.

Dr. Mathieu Bourdenx, Group Leader at the UK DRI at UCL, said:

“Our project aims to uncover how genetic and environmental factors work together to maintain the delicate balance of condensates within cells. We will investigate the interaction between interstasis and established protein-clearance mechanisms to better understand how neurons remain healthy throughout ageing.”

Professor Jernej Ule, Van Geest Professor of Neurodegeneration Research and Centre Director of the UK DRI at King’s, said:

“Many proteins associated with disease can bind to RNA, and several of these proteins form harmful clumps in neurodegenerative diseases as a result of genetic mutations or age-related stress. By studying interstasis, we may uncover new principles that cells use to detect protein imbalances at an early stage and reduce the formation of toxic protein aggregates.

Source: https://www.ucl.ac.uk/brain-sciences/news/2026/jul/ps38m-awarded-study-protective-mechanisms-against-neuron-damage-and-ageing