Congratulations to Assistant Professor Denis Titov on receiving the Biophysical Journal’s 2025 Paper of the Year - Early Career Investigator Award.
Denis Titov
The annual award recognizes an outstanding paper by an early-career scientist published in the Biophysical Journal, the Biophysical Society’s flagship journal, which publishes research that brings quantitative insight to questions spanning the molecular, cellular, systems, and whole-organism scales. Titov—who is jointly appointed in the departments of Metabolic Biology and Nutrition and Molecular and Cell Biology, and the Center for Computational Biology—uses experimental methods and computational biology approaches to understand how metabolism is organized and controlled, and how it breaks down in aging and disease.
Titov’s winning paper, published in the journal's May 2025 issue, offers new insights into glycolysis, one of the oldest metabolic pathways that is described in every biochemistry textbook. Nearly all organisms use glycolysis to break down glucose to produce ATP, an important source of cellular energy, and other cellular building blocks. However, scientists still don’t fully understand how the process is regulated to prevent the concentration of intermediate molecules from spiking or dropping too low. Decades of biochemical studies, including many led by UC Berkeley researchers, have identified how a network of molecules known as allosteric regulators binds to the enzymes that drive glycolysis.
Researchers have long suspected these regulators are essential to controlling the process, but their exact function within cells remains an unanswered question among metabolic biologists. To tackle this, Titov and former postdoctoral researcher Mangyu Choe built the first detailed mathematical model of glycolysis using a system of differential equations. The model is based on decades of laboratory kinetic data and estimates of 172 discrete parameters spanning dozens of datasets.
Using their model, Titov and his collaborators can accurately predict any cellular function for allosteric regulators of glycolysis. They also discovered that allosteric regulation of glycolytic enzymes by ATP, ADP, and inorganic phosphate prevents glycolysis from producing extreme metabolite concentrations that would cause the cell to explode. Titov notes this proof-of-principle approach offers researchers a blueprint for decoding allosteric regulators in other metabolic pathways.
“The work sets an important benchmark for the field and will shape how we think about cellular energy metabolism going forward,” Vasanthi Jayaraman, the Journal’s editor-in-chief, said of Titov’s research.
Read Titov’s award-winning paper in the Biophysical Journal.