A brand-new faculty member is shaking up the way researchers understand cellular systems.
Computational biology Professor Bercem Dutagaci, who started at UC Merced in January, developed simulations of bacterial cells as a new way of looking at how RNA and proteins self-organize inside the cells. Her most recent work demonstrates that the insides of cells are organized at complex levels of order, instead of a chaotic stew of molecules.
Dutagaci studies the process of phase separation, in which a well-mixed solution of macromolecules such as proteins or nucleic acids spontaneously separate into two phases: dense and dilute. She details the work she completed while a postdoctoral researcher in Professor Michael Feig’s lab at Michigan State University with the collaboration of MSU Professor Lisa J. Lapidus in a new paper published in the high-impact journal Elife.
“Phase separation is a key mechanism for forming membrane-less organelles, which are responsible for a number of functions in cells, such as metabolism, chromosome organization, chromosome segregation, cell division, pathogenesis and DNA replication, translation and transcription,” Dutagaci said. “These are the processes that help cells live.”
It is important to understand how these organelles work because they are much more responsive than membrane-bound ones to changes in their environment including temperature or nutrient availability. Understanding how these processes of self-organization work could help prevent diseases.
Until Dutagaci developed her coarse-grained simulation of a bacterial cell, scientists had only been able to simulate a fully atomistic model of cellular environments on nanosecond time-scales, which required massive calculations. Dutagaci’s coarse-grained model allowed her to increase the time-scale of simulation to the millisecond range while still covering the spatial scales relevant for biological cells. That allowed her and collaborators to see the effects of phase separation, which they experimentally verified.
The work also demonstrates that phase separation may be a more general phenomenon with multiple causes, she said. Dutagaci’s work reveals that phase separation is more dependent on the concentrations, sizes and electrostatic charges of proteins than previously thought.
“The simulation results were initially puzzling as they suggested a much more general phenomenon than what we knew from previous work,” Feig said. “There are always doubts that simulations generate nothing but fantasies, but in the end, we could confirm the idea via experiments and convince ourselves that what we saw in the simulations was real. Bercem’s persistence — and all of the team’s efforts to get to the bottom of this story despite many restrictions in a pandemic year — were truly heroic.”
Molecular and cell biology Professor David Ardell, who helped recruit Dutagaci to UC Merced, said he is excited about her work.
“Understanding how cells work at this level is a whole new frontier in molecular cell biology,” Ardell said. “It seems there is non-random organization inside cells, but it’s really hard to study. Her work shows that the subcellular domain is highly organized, but according to principles we barely understand.”
Dutagaci, a member of the Department of Molecular and Cell Biology in the School of Natural Sciences, is teaching an undergraduate course this semester and is looking for a postdoc and graduate students to work with. She said she plans to continue studying phase separation as soon as her new lab is set up.
“It’s important to be able to understand these processes,” she said. “Phase separation might be much more universal a phenomenon than we had thought.”