Nearby, others work at computers, transforming equations into models that could one day unlock secrets behind neurodegenerative diseases like Alzheimer’s. In this interdisciplinary hub, numbers and algorithms converge in a quest to better understand the brain’s immune system and revolutionize how we treat its most devastating disorders.
Supported by a $307,000 National Science Foundation grant, the students use agent-based models—computational tools that simulate interactions between cells and their environment—to study microglia’s role in neurodegeneration. These models allow them to explore the complex and vast pathways of cell behavior.
Microglia are crucial for brain health, helping to regulate development, fight infections, and more. “But when these immune cells ‘go rogue,’ they can contribute to neurodegenerative diseases like Alzheimer’s,” explains Kamila Larripa, Mathematics professor and the project’s principal investigator.
Understanding why microglia behave abnormally remains an open question. Larripa’s lab uses mathematical models to explore this mystery. Those models allow the researchers to simulate the cells’ environment and see how changes such as temperature or energy sources impact the cells’ behavior. Models also capture interactions between different cell types. For instance, neurons can signal to microglia, prompting them to move closer and clear debris. Similarly, microglia can release lactate, which neurons use as an alternative energy source.
This research is important because Alzheimer’s does not have a definitive cause or a cure, says Cheyenne Ty, a senior computer science major and one of the student researchers. “Alzheimer’s research is also very expensive and time-consuming, since it relies on raising mice or getting tissue from Alzheimer’s patients. Our models can provide a faster and cheaper way to test hypotheses about Alzheimer’s progression without any organic tissue. On top of this, our model can serve as a basis for other researchers that want to model more specific characteristics of microglia or Alzheimer’s disease.”
During the first phase of the research, which began last year, students investigated how factors like temperature affect microglia behavior and Alzheimer’s progression. Their findings were recently published in Spora: A Journal of Biomathematics, a peer-reviewed journal, and presented at the 2024 CSU Research Competition and the American Physical Society Far West Conference. Additional research by Larripa—which explores how the cells process glucose and lactate, linking metabolism to inflammation and highlighting the role of lactylation in regulating these processes—was also recently published in the Journal of Theoritical Biology.
This year, the team has expanded its research. One student is also leading a subproject to develop methods for automatically identifying and classifying microglia from microscope images using machine learning. They plan to present their latest findings at the 2025 CSU Research Competition in April.
Students of all levels and disciplines participate in the research. Many did not have prior biological knowledge and they have become quite expert, Larripa explains. “It is a really interdisciplinary project.”
This collaborative effort has been particularly rewarding for Ty. “I've learned how much our disciplines compare and contrast through our individual skills and strengths,” she adds. “None of us have a strict background in biology, so it's also been an amazing experience learning about an unfamiliar subject together.”
“Having the opportunity to learn about a topic that wouldn’t come up in my undergraduate classes is also amazing since it opens my eyes to other fields of study,” says Ty. “This helps me connect my interest in computer science to fields that are not tech-related, making me feel more confident about what my future career can look like.”
It’s also had a profound impact on her career aspirations. “Being able to apply my knowledge in computer science to this research has shown me that I don’t need to be in the tech industry to have a fulfilling career. I can apply what I have learned for my degree to fields that people don’t think about when applying for computer science jobs.”
For Abigail Penland, also a senior computer science major and student researcher, the study acts as a bridge between fields.
Originally, this work didn't really connect with her idea of her future, she explains. “I've grown to really enjoy these subjects and I look forward to exploring similar work in the future. There is something so fulfilling about navigating through spaces you aren't familiar with and finding yourself within the unknown. My work here has not just given me new knowledge, but also the confidence that I can learn and grow wherever I go.”
“I believe that my experience on this project will open doors to these new fields and I'm excited to see where they will take me,” Penland says.