The organelles are the organs of the cell: the ribosomes, centrioles, nuclei and so on. Most of these organelles serve vital – and well-understood – functions in cellular activity. “They’re there to do certain functions. For instance, mitochondria generate the energy that everything runs on,” said Aleksei Aksimentiev, a professor of physics at the University of Illinois at Urbana-Champaign, in an interview with Aaron Dubrow at the Texas Advanced Computing Center (TACC). But recently, stranger organelles came to light – and supercomputers are helping to illuminate their function.
“What is common to all of [the organelles] is that they’re surrounded by a lipid membrane,” Aksimentiev said. “What people recently discovered is there are organelles that don’t have lipid bilayers. They assemble spontaneously in the form of droplets. And those organelles have particular functions.”
These odd organelles, now called biological condensates, have been speculated to relate to DNA repair and aging, impacting the progression of diseases like ALS. “Let’s say you have DNA and it suddenly has a break,” Aksimentiev said. “It’s usually a really bad thing, because it cannot replicate, but there’s a machinery that will come and repair it. A bubble of condensate forms that miraculously attracts only the molecules that are required to repair the DNA. There are all kinds of different condensates and they all recruit the right molecules somehow.”
The mechanism of this repair, however, remains unclear. “We don’t know exactly how it works,” Aksimentiev said. “I’m specifically interested in how this recruitment happens, and how molecules recognize other molecules.”
To shed light on how these condensates function, Aksimentiev turned to the Frontera system at TACC, a Dell EMC system that delivers 23.5 Linpack petaflops of computing power and placed 8th on the most recent Top500 list of the world’s fastest supercomputers. He applied Frontera to run intensive molecular dynamics simulations – millions of atoms for milliseconds of simulated time. While the condensates posed a particular challenge for such simulations due to their “partially disordered” structure, the researchers were able to pin down a biomolecular condensate.
This condensate in question (called “fused in sarcoma,” or “FUS”) is involved in regulating gene expression activities. The simulations allowed the researchers to see the condensate’s phase separation properties, revealing its susceptibility to mutations and other descriptive attributes. The researchers also found that the condensates could be represented by a polymer physics model, opening the door for further computer modeling.
Header image: a biological condensate, as modeled by the simulations. Image courtesy of Han-Yi Chou, University of Illinois, Urbana-Champaign.
To read the reporting from TACC’s Aaron Dubrow on this research, click here.