How does our brain create so many different types of nerve cells? And does metabolism affect the growth of brain tumors? Two researchers at UMC Utrecht are tackling these questions. Their innovative research could ultimately contribute to better treatments for a range of conditions. Both researchers have received a prestigious ERC Starting Grant to pursue their work.
UMC Utrecht researchers and assistant professors Kimberly Siletti and Evita Wiegers will each receive at least 1.5 million euros over the next five years. With these ERC Starting Grants, they can further explore their promising ideas. What exactly will they study, and what do they hope to achieve?
Project 1: how do different types of nerve cells emerge?
The brain contains an extraordinary diversity of neurons (nerve cells) that form complex neural circuits. Yet, how the brain generates and connects so many different cell types remains poorly understood.
“In our previous work, we found astonishing cell type diversity across the brain, which raised new questions about how the brain generates and wires so many different cell types,” says Kimberly Siletti.
Together with her research group, she now wants to understand how the development of neurons and their connections influence each other.
“We should not only be able to make the right nerve cells, but also be able to connect them properly for possible new treatments.”
Following neural connections
To do this, the researchers will track how neurons and their connections change during development by studying them in the visual system of mice. By selectively disrupting certain connections, they will investigate how this affects neuronal development and which molecules are involved.
The research could reveal new principles underlying brain development. “I hope that within the next five years, we’ll better understand how the incredible diversity we’ve recently discovered in the brain relates to the brain’s circuitry,” Kimberly explains.
In the longer term, these insights could also further research into neuropsychiatric, neurodevelopmental, and neurodegenerative disorders.
“Some ongoing efforts to treat neurodegenerative diseases rely on properly reproducing and wiring lost cells,” Kimberly says. “I hope that my team will discover new principles that will aid these efforts.”
Project 2: does metabolism help brain tumors grow?
In order to grow, brain tumors change the way they manage energy. One substance that plays an important role in this process is lactate. It is produced when nutrients are converted into energy.
Researchers, however, still do not fully understand how brain tumors produce, take up, use, and remove lactate. Standard MRI scans allow doctors to see brain tumors in great detail. However, they reveal very little about what is happening inside the tumor’s metabolism: the processes it uses to produce and use energy from everything we eat and drink.
“When we want to know whether a treatment is working, we often look at whether the tumor is growing,” Evita Wiegers explains. “But before a tumor can develop, biological changes first have had to take place in its metabolism to make this growth possible.”
“If we can monitor the metabolism during or immediately after treatment, we will better understand how a brain tumor grows.”
Mapping lactate in brain tumors
Evita and her research group will combine several MRI techniques for the first time to map how lactate moves through brain tumors in patients.
Alongside conventional images of the tumor, this will provide a kind of dynamic map showing how the tumor manages and uses energy. The researchers will then combine all of this information in a mathematical model.
“If we succeed in merging all these new techniques and can measure the different pathways of lactate in individual patients, we will have achieved something very important within five years.”
Evita believes this approach could create new opportunities for personalized care. “If we can closely monitor changes in lactate during or immediately after treatment, doctors may gain a better understanding of how a brain tumor grows in an individual patient. That could potentially help them determine sooner whether a treatment is working.”
Eventually, the method could also be useful for other types of cancer and neurological conditions in which metabolic changes play an important role.
About the ERC Starting Grant
The European Research Council (ERC) was established by the European Union in 2007 and funds groundbreaking and innovative scientific research through several grant programs, including the ERC Starting Grant. This grant is specifically designed for talented researchers early in their careers, helping them to establish their own research groups and develop ambitious new research ideas.
