One critical process that Wu is examining is autophagy, a mechanism by which cells break down and recycle their own components. It is a crucial means of discarding damaged proteins and organelles that might otherwise cause disease.

“Autophagy is one of the cell’s most sophisticated recycling systems. It enables the cell to manage stress, fight infections and stay healthy,” says Wu, professor of biochemistry at Umeå University.

Autophagy plays a key role in many biological processes. Disruptions in this process have been linked to a number of conditions, including neurodegenerative diseases such as Parkinson’s and Alzheimer’s, as well as cancer.

“If autophagy doesn’t work as it should, harmful proteins can accumulate in brain cells, as occurs in Alzheimer’s,” Wu explains.

His research team hopes to learn exactly how autophagy is regulated, enabling them to identify new targets for drug development.

Internal logistics

Autophagy is a specific form of intracellular membrane trafficking, which is the cell’s internal transport system, determining how molecules and proteins move between different parts of the cell and to its surface. Autophagy involves the dispatch of cargo specifically to lysosomes – the cell’s “recycling bins.” Alongside autophagy, Wu has also studied membrane trafficking.

“Think of it as a network of roads and highways, in which the cell sends signals and materials to the right place at the right time.”

Membrane trafficking is essential if the cell is to function as it should. Proteins and lipids must be transported to the proper locations to perform their tasks. When this transport is impaired, disease may result, including cancer, metabolic conditions and certain genetic disorders.

Lysosomal membrane trafficking is the transport of materials to, from, and within lysosomes – organelles that break down and recycle biomolecules. Recent research has shown that this process becomes vulnerable as we age, increasing the risk of neurodegenerative diseases like Alzheimer’s and Parkinson’s.

“Our aim is to understand the exact mechanisms behind this process, enabling the future development of more targeted therapies for neurodegenerative diseases. We recently discovered that some autophagy proteins have an additional function – they help to keep the lysosomal membrane intact, in addition to their normal role in autophagy.”

One area of the team’s research focuses on enzymes called small GTPases, which act as molecular switches to control transport.

“If we can manipulate those enzymes, then in theory we’ll be able to control the cell’s internal logistics and potentially correct certain pathological conditions,” he explains.

New chemical tools

Wu’s research team is developing advanced chemical tools to understand these complex biological processes.

 One of the most innovative tools they have created involves light-controlled chemical molecules that allow specific proteins in living cells to be activated or inactivated with extreme precision.

I’m determined to continue exploring the innermost secrets of cells and developing innovative tools. We ought to be able to control the inner logistics of cells and remedy certain pathological conditions.

“We’re using small molecules and light to control cellular functions with unparalleled precision. This enables us to study processes in real time and with a degree of control we previously only dreamed of.”

These tools not only aid a deeper understanding of fundamental cell mechanisms; they also offer new scope for targeted disease therapies.

A long-term aim of Wu's research is to identify new drug targets and develop innovative treatment methods.

“We have used special tools that combine small molecules and light control to manipulate cells with a high degree of temporal and spatial precision. These tools can be very useful in synthetic biology, where organisms are altered or created for medical or industrial purposes. This is truly an incredibly exciting time to explore a new field,” says Wu.

Recognition and future research

Wu was born in China. His research has gained both national and international recognition. He was chosen as a Wallenberg Academy Fellow at Umeå University in 2016, where he became a professor in 2018. His grant has been extended, providing his research team with the resources to explore new frontiers.

“This support is crucial. Scientific research takes time, and we need long-term investment to make real breakthroughs,” he says.

Driven by a continued strong desire to understand the innermost mechanisms of cells and with access to advanced research methods, Wu and his team are determined to continue uncovering the secrets of the cell and developing innovative tools.

“I am driven by curiosity. The more we learn, the more questions arise. That's what makes science so fascinating.”

Text Elin Olsson
Translation Maxwell Arding
Photo Johan Gunséus