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May 10, 2018

Pam Marshall, associate professor of genetics and cell biology, was part of an interdisciplinary team of researchers at Arizona State University and Columbus State University to publish new findings on calcium homeostasis in the April issue from Mathematical Biosciences.

The article, titled “Bifurcations and Limit Cycles in Cytosolic Yeast Calcium”, details the research on this fundamental cellular process in yeast, and the mathematical models used to describe the cellular response observed during the research process.

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ASU’s new Interdisciplinary Arts and Sciences College spoke to Marshall for a deeper dive into what research was and how it will impact in the future.

Question: What is important in calcium homeostasis? What is its impact on our body and our health?

Reply: Yeast is a well-known microorganism that lives in the immediate human environment, is part of our food preparation, bread and beer, but has also long been a model system where fundamental questions of biology can be studied. Yeast colonies are made up of a large number of individual yeast cells and can be found naturally in soil, plants, and as animal and human parasites.

These colonies are able to survive and thrive in a wide variety of environments, some of them quite extreme, such as very salty environments. The mechanisms by which these organisms are able to maintain acceptable internal conditions against external changes, homeostasis, is of course of great interest. The complex structure of these mechanisms can be more easily studied in yeast and other simple organisms, but the results are often applicable to human health. The inner workings of heart cells have a lot in common with the way yeast controls its internal environment. We seek to better understand yeast calcium homeostasis as a way to unlock knowledge about our own body and as a way to create new industrial processes where yeast and similar organisms play a role.

Q: What were your discoveries? Why are they important?

A: The key objective of our research is to understand the dynamic characteristics of calcium homeostasis. After a disturbance in its environment, such as a sharp increase in the concentration of surrounding calcium, an organism will eventually adapt to it, but the process is not immediate. In addition, sometimes organisms may not respond in one way and may eventually attain one of many different stable states; that is, their response may present a bifurcation. Under other specific conditions, the response may indicate oscillations, alternating between different conditions and not settling in one of them. Observing and predicting the presence of bifurcations and oscillations is always a striking result and an important and direct way to verify our understanding of a system. Knowing when these characteristics appear also opens up the possibility of creating control mechanisms: in medical applications, we would like to find ways to ensure that we reach a desired end target state.

What this particular work has achieved is the integration of three different research methods with the aim of understanding calcium homeostasis.

1. Experimental work where the calcium intake of a group of yeast cells is measured.

2. Mathematical modeling which, using the known properties of yeast, predicts the possible presence of bifurcations and oscillations.

3. Physical modeling which links the predictions at the single cell level of the mathematical models with the means for entire populations observed in the experiments.

The mathematical model that we used indeed predicts the presence of peculiarities of bifurcations and oscillations in the yeast response. Our physical modeling indicated that the bifurcations would be observable as strong changes in the mean response of yeast against exposures to increasing concentrations of calcium in the environment. Finally, we confirmed that such changes were observed in real experiences.

Q: How will your findings impact future research?

A: One of the most important aspects of this work is the avenues it opens for future investigations. We are currently exploring many avenues of research on the basis of these initial results. We are exploring new experimental methods that would better reveal the details of the equilibrium approach. We are trying to refine the mathematical models that would allow us to better understand the nature of the processes.

Q: Tell us about the interdisciplinary nature of research.

A: An exciting aspect of this project was that it required the collaboration of three faculty members from the School of Mathematical and Natural Sciences. I am a yeast biologist who, with a group of my students, carried out the experiments at the heart of the project. Haiyan Wang is a mathematician who, together with an external collaborator, Guihong Fan, currently at Columbus State University in Alabama, performed the mathematical analysis of the model and established the presence in the model of bifurcations and oscillations. Francisco J. Solis, a physicist, integrated mathematical and biological work and analyzed the experimental results in the light of mathematical findings.

See the full research article.


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