Falkenberg has long been fascinated by mitochondria. These small units in our cells have numerous important functions and are sometimes called the powerhouses of the cells because they convert what we eat into the energy our body needs. Uniquely, mitochondria have their own DNA, which differs from the DNA in the cell nucleus.

But when the mitochondria malfunction, diseases can result. This is often due to problems in the replication of mitochondrial DNA (mtDNA) that occur when the genetic material is renewed.

These processes attracted Falkenberg’s interest almost 30 years ago, and they have been the primary focus of her research ever since.

“At that time, very little was known about the mitochondria, and there was hardly anyone who had researched mtDNA replication. My research team was among the first to enter the field, and has become one of the leading groups in the area,” she says.

Multiple causes and symptoms

One of the puzzles that still baffles researchers is that mitochondrial diseases can have so many different causes and symptoms. This is true even in cases where genetic changes, or mutations, have occurred in the same gene.

“That’s why it’s so important to fully understand how replication of mitochondrial DNA works. This is our major research goal, because there’s still so much, we don’t know about the processes. And this lack of knowledge means we don’t know how to treat or avoid the diseases,” she says.

Mitochondrial diseases are serious conditions that gradually break down tissues, organs or body functions. Above all, they affect tissues and organs that need a lot of energy, such as the muscles and the brain. The diseases are rare individually, but not as a group. About one in 5,000 people worldwide suffers from some form of mitochondrial disease, many of which are fatal. Some appear at birth, others much later, and there are still no cures or effective therapies.

Falkenberg is well acquainted with the various diseases and their consequences. Over the years, she has been in contact with patients and support organizations, as well as biomedical companies striving to translate research findings into medicines.

“For me, the ultimate goal is clear. Everything we do is aimed at enabling cures to be found for these diseases. I hope the foundation that our research is building will one day lead to that goal. What we are working on feels so important, which is a great motivator,” she says.

Increasing the level of healthy DNA

In mitochondrial diseases, mutations may arise during the replication of DNA, leading to levels of healthy mtDNA becoming far too low. Having enough healthy copies of mtDNA has proven to be more important than how much mutated mtDNA is present. This opens the way for new approaches to treating the diseases.

“The diseased mtDNA copies usually do not contribute to normal function, and disease arises because there are too few healthy mtDNA copies. The key is therefore to increase all the copies, to raise the level of healthy mtDNA,” she says.

This very process – increasing the copy number of healthy mtDNA in the cell – is one of the key processes in the fight against mitochondrial diseases that Falkenberg’s research team will continue to explore. The researchers have already conducted experiments with animal models and in vitro systems, in which they found ways to raise the levels of healthy mtDNA.

The project will address several unanswered questions, including why DNA replication in the mitochondria sometimes gives rise to shortened variants of mtDNA.

“The purpose of all the questions we ask is to map each step, every aspect of the basic mechanisms behind DNA replication. That knowledge is needed to understand how and where we can intervene in the processes and create medicines that make a difference for patients,” she says.

For me, the ultimate goal is clear. Everything we do is aimed at enabling cures to be found for these diseases.

Falkenberg’s research team has focused extensively on mitochondrial diseases linked to a particular gene: the POLG gene, which encodes the mitochondrial DNA polymerase. But their findings may have even wider significance.

“We hope our basic research will improve our understanding of several of mitochondrial diseases. We also believe it can provide important insights into processes related to ageing. The amount of healthy mtDNA declines as we get older and has been associated with age-related diseases such as Parkinson’s and diabetes,” she says.

More an interest than a job

Falkenberg does not come from an academic family and never planned to become a researcher. But once she encountered the world of research, her career choice felt entirely right.

Research is so enjoyable, she points out, that sometimes it can be hard to let go.

“My daughter sometimes tells me at the kitchen table that it’s time to stop talking about my research. But my work is such fun! In fact, it doesn’t even feel like a job, but more like an interest that enables me to indulge my curiosity, test my ideas and see exciting results,” she says.

Text Ulrika Ernström
Translation Maxwell Arding
Photo Johan Wingborg