Kalle
Kalle
Cambridge Rindge & Latin School
Cambridge, MA
Mentors:
Nirmala Rayan & Alec Wysoker
Stanley Center for Psychiatric Research | McCarroll Group
Kalle joined the ӳý Summer Scholars Program eager to explore how computational biology can help uncover the molecular underpinnings of brain health and disease. He became part of the Brain Initiative Cell Atlas Network (BICAN), a large collaborative project creating a comprehensive reference map of brain cell types. Kalle’s focus was the dorsolateral prefrontal cortex (DFC) — a brain region essential for decision-making, attention, and working memory — and the immune cells that help maintain its health.
Using single-nucleus RNA sequencing (snRNA-seq) data from postmortem human brain tissue, Kalle investigated how microglia, the brain’s resident immune cells, differ between individuals based on age and sex. After training in R and the Seurat analysis package, he learned to integrate data from multiple donors, perform quality control, cluster cells, and annotate specific immune subtypes.
The results revealed seven distinct immune clusters, including canonical microglia and a specialized “immune-alert” population. Age-related differences emerged: older donors showed reduced expression of NAV2, a gene linked to Alzheimer’s disease risk, and increased FKBP5, associated with inflammation. Sex differences were also clear — female donors had elevated expression of CD74, tied to antigen presentation, while males showed higher levels of DSCAM, linked to synaptic function.
These patterns provide new insight into how demographic factors shape immune cell biology in the brain, offering potential clues for understanding susceptibility to neurodegenerative diseases. The work also contributes to BICAN’s mission of building a publicly accessible atlas of brain cellular diversity.
Reflecting on the summer, Kalle shared, “BSSP was an incredible opportunity… I really enjoyed working with and learning from my mentors, my peers, and other scientists.” The experience not only deepened their technical skills in large-scale data analysis but also reinforced their interest in pursuing neuroscience research that bridges computational and experimental approaches.
