What begins as a co-op experience can sometimes change the trajectory of a career — that’s exactly what happened to UW alum Kritika Grover. During her work term at the SickKids Research Institute, Kritika demonstrated remarkable curiosity and initiative, contributing to an important study on cerebral palsy. Murto Hilali, who completed his co-op term before her, also played a significant role in the project. Now, both students are credited authors in a paper published in Nature Genetics. The paper, “Comprehensive whole-genome sequence annotation to elucidate the genetic architecture of cerebral palsy,” uses AlphaFold, an artificial intelligence program that predicts protein structure, to explore how gene variants affect the development of cerebral palsy.

For Hilali, a fourth-year biotechnology/economics student, this opportunity began early in his co-op term when he was assigned a project to explore how AlphaFold could be applied to genes associated with cerebral palsy. His curiosity quickly led him to identify a promising application of the tool as well as a gap in an ongoing paper his lab was working on. His insights earned him an invitation from his supervisor to join the research team and contribute directly to the paper.

His work laid the foundation for Grover, a fourth-year biochemistry student minoring in computing, who carried the project forward when Hilali’s co-op term ended. At the time, Grover had been hired as a research assistant with no formal background in bioinformatics. As she recalled, she approached her mentor with “no experience, just hopes and dreams.” Despite this, her enthusiasm and willingness to learn allowed her to take on the challenge of the project. She expressed her interest in bioinformatics to her supervisor, who directed her to this exciting opportunity. With guidance and dedication, Kritika quickly became a valuable contributor to the study, even taking on the responsibility of analyzing gene variants with AlphaFold.

The team used AlphaFold, a deep learning model developed by DeepMind, to predict the 3D structures of proteins based on genetic sequences. While researchers typically crystallize the structure of unaltered proteins, Grover’s work focused on rare clinical variants from patients at SickKids Hospital. “We wanted to be able to see the structure of what these proteins look like when there’s mutations in the genes,” she explained. Using AlphaFold Multimer — a tool that predicts how two proteins interact — Grover analyzed the protein-protein interaction interfaces, focusing on changes caused by mutations. They analyzed metrics like the number of amino acid residues involved at the interaction site and the distance between alpha and beta carbons. Their findings revealed that mutations often weakened these interactions by decreasing the size of the interface and increasing the distances between key residues. This disruption could have significant consequences for protein function, shedding light on how genetic mutations might contribute to diseases like cerebral palsy.

Not only did this project contribute to a body of research important for understanding the biology behind rare brain disorders, but it also transformed Grover’s academic and career path. “This project really inspired me and unlocked this new passion I had for computational biology,” she said. Motivated by the experience, she added a Computing minor and extended her degree by an extra term to build a stronger foundation in the field of bioinformatics. After attending a SickKids seminar featuring a speaker from Weill Cornell, she decided to pursue her PhD in computational biology there. “It was a butterfly effect,” she said. “And now I’m here for my PhD — and it’s all because of this project.”