One of biology’s most mysterious puzzles has long been how cells talk to one another. These signalling processes underlie not only basic physiological functions, but more complex neurological functions as well. Now, researchers at the University of California San Diego (UCSD) have unveiled a tool that could transform our ability to simulate and study these networks: Spatial Modelling Algorithms for Reactions and Transport (SMART).
The software package SMART is designed to simulate the molecular interaction that underlies cell signalling networks. Due to their three dimensional nature and the complex biochemical environment in living cells, biochemical events in these networks are often governed by cascades that are complicated. SMART is more precise, efficient and scalable than traditional tools with little success at capturing these intricacies.
Bridging Complexity with Precision
Dr. Emmet Francis, who was a postdoctoral fellow in the American Society for Engineering Education, along with Professor Padmini Rangamani of the Department of Mechanical and Aerospace Engineering at UCSD, lead the development of SMART. Justin Laughlin, Ph.D., a former graduate student in Rangamani’s lab completed the initial coding of the software.
At multiple biological scales, SMART allows researchers to model cellular responses. Early applications have been to study how cells respond to adhesive signals, simulate the dynamics of calcium release in neurons and cardiac muscle cells, and to explore the production of ATP by mitochondria. In these examples, we show that SMART is a versatile tool, used to answer questions that extend from subcellular interactions to organ level processes.
Among the simulations, one spotlighted calcium release in cardiac muscle cells, a critical step in heart contraction. It’s particularly powerful for researchers looking at diseases involving heart disease and other conditions where calcium signalling is important.
The SMART project reflects the power of interdisciplinary collaboration. While the core development took place at UCSD, it is part of an ongoing partnership with the Simula Research Laboratory in Oslo, Norway, led by Dr. Marie Rognes. The tool benefits from insights across disciplines such as pharmacology, systems biology, and engineering.
The research also drew on diverse funding sources, including the National Science Foundation, the Kavli Institute of Brain and Mind, and the European Research Council. These contributions underscore the global interest in advancing computational tools for biological research.
Applications and Future Directions
With SMART it can bridge the gap between computational modelling and biological experimentation to become a useful tool for researchers. With this, we can accelerate the drug development, understand the disease mechanisms and create new medical engineering frontiers.
Each of the challenges that the software is implemented for can be addressed by the open-endedness of the design, which permits continual refinement and expansion in response to the evolving challenges in the field. The team hopes the group called SMART will not only help explain how the cell misbehaves but may also lead to new targeted therapies for complex diseases.
With tools like SMART, the bounds of what we can accomplishing in computational biology expand, discovering new biologically relevant insights into basic processes that support life. This development opens an exciting chapter in the ongoing effort to understand life at its most granular level, for researchers and engineers alike.
