"I was the only one in the room. The number I'd been looking for showed up on the mass spectrometer. It was the most intense dopamine rush I'd ever had."
This is how Uche Medoh, winner of the 2025 Science & SciLifeLab Prize for Young Scientists, describes a turning point in his life – a moment when he solved a 50-year puzzle in his field, uncovering the machinery behind BMP, a molecule with protective effects against various disorders.
Understanding jhow BMP is made, which scientists hadn't known about for decades, could help them increase its levels to treat multiple diseases – a promising idea. It could potentially be useful in treating ALS, Parkinson's, and Alzheimer's, for example.
Just a few weeks before, however, Medoh, a Science Fellow & Principal Investigator at the Arc Institute, had been much less joyful. During experiments late one night tying up separate work studying CLN5 – a genetic risk factor for neurodegenerative disorders – he learned that a model he'd put forward to describe CLN5's function was wrong.
Medoh had been studying CLN5 for over two years because mutations in it cause a lethal disorder in children called Batten disease. The disorder involves problems with lysosomes – cells' recycling and waste-processing centers.
Nobody knew exactly how CLN5 functioned.
"I believed that studying CLN5 could reveal an important biochemical process … with broader lessons for understanding complex neurodegenerative diseases," wrote Medoh in his prize-winning essay in the 13 November issue of Science.
But after the model he'd put forward to explain CLN5's function failed, he needed to take a step back and dwell on the results. "The epiphany I had was that while my model was wrong, the data it provided were still true."
The data suggested a connection between CLN5 and lipid breakdown in lysosomes, the compartments where BMP accumulates. "When I first started studying CLN5," said Medoh, "I thought BMP was totally separate." But after this pattern appeared, he was compelled to ask: "Is CLN5 the BMP synthase?"
Medoh designed a mass spectrometry experiment where, if a certain number showed up, it would prove that CLN5 was the machinery behind BMP. In this experiment, the mass spectrometer detected the formation of BMP in a test tube containing only the purified CLN5 protein and a molecule that protein works on.
Sure enough, while he was alone in the room with the instrument, the exact number appeared. It was an incredible moment.
"Everything moved very quickly after I made the connection between BMP and CLN5," he said.
" We are excited to award the grand prize to Uche Medoh. What stands out about his essay is that when his data did not fit his model he was able to accept this and let his data lead him to a new exciting discovery," said Valda Vinson, executive editor of the Science family of journals.
"The Science & SciLifeLab Prize for Young Scientists not only honors exceptional talent, but also underscores the importance of curiosity and the pursuit of new knowledge in driving groundbreaking discoveries. Paired with their ability to communicate new concepts with clarity and enthusiasm, these young researchers give inspiring examples of how progress in science is rooted in a commitment to venture into the unknown by generating new facts, use logical reasoning and collaborate," said SciLifeLab Director Jan Ellenberg. "We are proud to support them as they take the next steps in their careers, and we look forward to seeing how their work will develop and inspire future generations."
Now that Medoh and his colleagues know more about the machinery that makes BMP, they want to identify proteins that help supply substrates for BMP production, among other factors. All of this will help them in efforts to increase BMP levels to treat disease.
He also continues to study how knocking out CLN5 makes some diseases worse, because BMP is not produced at sufficiently protective levels. In some cases, his research team is also seeing that knocking out this gene improves disease outcomes.
"There's so much you can study with regard to BMP," said Medoh, who explained that it touches most diseases in some form. "I think the discovery of CLN5's role ushers us into a new era of BMP biology where we can learn how to modulate it in ways that will be beneficial across a range of diseases."
Cancer cells, for example, rely on the lysosomes where BMP accumulates, especially as they live in nutrient-scarce environments. And viruses need BMP to escape disposal by the cells.
"There's so much to study – so many diseases for which understanding this molecule is important and could make a difference," said Medoh. "This is a new field, ripe for individuals with diverse talents and expertise."
2025 Winners
Liam Lachs is a winner for his essay, "Balancing between evolutionary rescue and extinction." Lachs received an undergraduate degree from the University of Galway, a master's from Vrije Universiteit Brussel, and a Ph.D. from Newcastle University. Since helping to conceptualize the CORALADAPT project, Lachs is now a postdoctoral research fellow in the Marine Spatial Ecology Lab at the University of Queensland. His research focuses on how coral reef management can leverage spatial variations in heat wave exposure and the adaptive potential of corals to support reefs in a warming world.
King L. Hung is a winner for his essay, "Oncogenes out of context." Hung received an undergraduate degree from the University of Washington and a Ph.D. from Stanford University. He started his postdoctoral fellowship at Scripps Research Institute in September 2024. His research focuses on the basic principles of how cells dynamically regulate genomic and signaling processes in cancer and tissue homeostasis.
Nitzan Tal is a winner for her essay, "Nucleotides on the frontline." Tal received an undergraduate degree from the Hebrew University of Jerusalem and a Ph.D. from Weizmann Institute of Science. She is currently a postdoctoral fellow at the European Molecular Biology Laboratory (EMBL Heidelberg), where she explores how bacteria respond to threats in their environment.
