Mathematics reveals how the size of cellular components is regulated

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Sebastian Persson uses mathematical models as a complement to experiments to study biological systems in his doctoral thesis. He has also developed software to more efficiently work with dynamic models.

Cell biological systems are complex, with many different components influencing their behavior. To understand from experiments alone how these systems are regulated is hard, but with the help of mathematical tools it is possible to build models to analyze how cell systems work.

Persson has collaborated with experimentalists in Germany and together they have explored how cellular components regulate their size and have come up with a good description that matches experimental data.

"Size regulation of cellular components occurs in most cells, and if this process does not work as planned, the risk of several diseases and premature aging increases. We wanted to understand the different strategies that the cells use to size-regulate cell structures, and modeling was needed since it is so difficult to reason about these processes. The final aim is that medicines should be able to be developed based on knowledge about size regulation."

New software to handle different kinds of models

To be able to simulate biological dynamic models, computers are needed. Since every model built is a hypothesis and the initial hypotheses are usually wrong, there is a need to work with and simulate many different models. So, the faster you can validate if a model works, the faster you can conduct your research. To make it easier to work with dynamic models, Sebastian has developed new software. The criteria were that it should be fast, and that it should be flexible.

Flexibility is important to be able to explore new research areas. For example, either mechanistic or data-driven models are used today, and both have their advantages and disadvantages. The idea with Persson's software is that it should be possible to combine both kinds of models in the same system, to compensate for the shortcomings with each approach.

The software PEtab.jl and SBMLImporter.jl have been published as open source since the spring of 2023 and are being used more and more, both by academia and industry, and are continuously being built upon.

Research—frustrating and satisfying

Persson has always liked mathematics but wanted to see an application for it and therefore studied a civil engineering program with a focus on biotechnology. During his bachelor's degree he realized that experiments were not his thing and did his bachelor's thesis in the systems biology group of Marija Cvijovic. There, he later started his doctoral position the week after he defended his master's thesis.

Having both mathematics and biology with him has been very useful in being able to communicate with experimentalists, and in understanding the literature for the systems that he studies.

"Overall, it has been a lot of fun doing a doctorate, but also very exhausting. School is so well defined, research something else entirely and when I started, I did not think much about how tricky it can be when there are no ready answers. You have to fail many times to realize what does not work, and that can be frustrating, but also very satisfying when it works, and you make new discoveries."

Now, a well-needed break awaits before Persson moves to London in March for a four-year postdoctoral position at The Francis Crick Institute, a biomedical research center. There, he will explore hybrid models of precisely mechanistic and data-driven models to study the cell cycle and try to understand how it is regulated by its surrounding cellular environment. It is still fundamental systems biology research, with the aim that it will lead to better medical treatments in the future.

More information: Enabling mechanistic understanding of cellular dynamics through mathematical modelling and development of efficient methods. gupea.ub.gu.se/handle/2077/83730

Provided by Chalmers University of Technology