If you can’t see inside a cell, let math find you! – USC Viterbi

Mathematical modeling can be used to understand the dynamics of cell function beyond what high-resolution images can display. Photo credit: Kate White.

Cells are the building blocks of life. In every human body, billions of them work together to perform the daily functions necessary for survival. Despite their importance and abundance, we know surprisingly little about how their internal functions work. This is for a very simple reason: they are too small to collect data reliably.

Using the limited information available, scientists typically create simulations of individual parts of the cell or organelles. But these mathematical-based models were designed by different people for a wide variety of applications, and therefore are often difficult to combine or compare. Researchers from the USC Michelson Center for Convergent Biosciences, in collaboration with colleagues at the University of California at San Francisco (UCSF) and the University of ShanghaiTech in China, have developed a system to combine these models in a compatible mathematical framework. They call it a metamodel, or a model of models. The metamodel acts as a universal translator between the models developed for each organelle, providing information on how they communicate and how changes in one affect the other.

“The ultimate goal is to understand what’s in a cell, how all the different rooms speak to each other and where they move over time,” says Kate White, Gabilan assistant professor of chemistry at USC Dornsife College. of Letters, Arts and Sciences. . “If we are able to figure this out, then maybe we can figure out how things go downhill during illness. “

White is the director of Pancreatic beta cell consortium, a collection of scientists from around the world dedicated to beta cell research through a unique interdisciplinary approach. A number of works by these metamodelling scientists have recently been published in the Proceedings of the National Academy of Sciences (PNAS), a prestigious academic journal.

“The goal of this consortium is not to model pancreatic beta cells just because they are interesting, even if they are very interesting,” said Barak Raveh, independent senior researcher at the Hebrew University of Jerusalem. “But if we can model these cells, we can model any cell. We can even model more complex systems, like all organs in the body. “

Raveh is one of the lead authors of the recently published PNAS article titled “Bayesian meta-modeling of complex biological systems through different representations.

He cited the interdisciplinary nature of the consortium as one of the main reasons for the success of the project.

“This collaborative environment is very unique in the world of science,” said Raveh. “We have people from very different scientific backgrounds: experimenters, computer scientists, artists, city designers. There is a certain Renaissance spirit in all of this, where you have to take into account completely different perspectives from yours.

“This project aims to create new ways of doing science. “

Carl Kesselman

The Pancreatic Beta Cell Consortium and its work with the USC Michelson Center have received wide support and acclaim.

“We are creating a community around cell modeling, where everyone depends on each other and the result we get is fundamentally multidisciplinary,” says Carl Kesselman, professor of industrial and systems engineering, computer science, preventive and biomedical medicine. . sciences at USC Viterbi School of Engineering.

“I think of it as a three-legged stool, where the three legs are computer modeling, experimental techniques, and data management,” says Kesselman, William M. Keck Chair in Engineering. “If you remove any of these pieces, the stool will fall off.”

Building on the success of this first project, the consortium intends to pursue its intercultural and multidisciplinary approach to research. Now that the metamodel has been proven successful – Raveh calls this article a “proof of concept” – the team will apply the concept of metamodeling to further research into the different methods of communication between organelles within the cell. A broader understanding of this process can provide crucial breakthroughs in understanding how cells respond to epidemics and drugs.

The most immediate application of their research on pancreatic beta cells revolves around the ability of these cells to produce insulin, which may revolutionize the treatment of diabetes. Theoretically, however, the method can be applied to a wide range of diseases, as all of them agitate the organelles of a cell in one way or another. The framework that the team built could have ripple effects that span across the field of medicine.

“Ultimately, this project is about creating new ways of doing science when it comes to how we manage, create and share data, and how to make it transparent and repeatable,” Kesselman said. “The question we ask ourselves is: How can we build systems that transform the way we think about doing science? “

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