Cambridge Rindge and Latin School
Stanley Center for Psychiatric Research | Daly Lab
In his application, Nebiyu told us he was keen to learn more about biomedical research and pursue computational work. He did just that under the mentorship of Kyle Satterstrom in a project that investigated the 3-dimensional location of missense mutations in autism. In this project, Nebiyu focused on two genes, SHANK3 and PTEN. SHANK3 codes for a protein that supports neuronal communication at synapses in the brain. PTEN codes for a tumor suppressor protein that regulates cell proliferation. In autism, mutations in PTEN can lead to the uncontrolled growth of white matter in the brain. Using mutation data collected by the Autism Sequencing Consortium, Nebiyu applied computational tools to determine whether the mutations in these genes were clustered or occurred at random. He downloaded predicted protein structures from AlphaFold and used a program called PyMOL to see where the mutations were located on the proteins. He then used k-means clustering to learn more about how these mutations clustered together in space, including comparing the mutations in people with autism to those in their siblings who didn't have autism. He found that in children with autism the mutations in the SHANK3 and PTEN proteins cluster together at higher rates than expected based on chance alone. When asked to reflect on his experience, he said: "BSSP taught me not only the skills to succeed, but it also helped me grow as a person in and out of the lab. Applying my knowledge and fostering the connections I made will prove to be invaluable to my interpersonal growth. I am thankful that BSSP harnessed this within me."