Sara Cotto Ortiz
MIT Department:
Chemistry
Faculty Mentor:
Matthew Shoulders
Research Supervisor:
Michael Xiong
Undergraduate Institution:
University of Puerto Rico, Rio Piedras
Biography
Sara Mia Cotto Ortiz is a rising sophomore majoring in chemistry at the University of Puerto Rico, Rio Piedras. Sara has always been interested in science, which she explored in high school, presiding over her school’s science club, graduating with High Honors, and receiving the Gregor Mendel Medal for excelling in biology. In summer 2024, Sara participated in a brief summer program at the University of Puerto Rico, Humacao, where she rotated labs and was introduced to coding and pipetting. At the end of the program, she worked alongside Dr. Nicholas Pinto, using electrospinning to create polymer nanofibers infused with antibiotics to treat wounds, and presented her work to the faculty. During her MSRP experience, Sara worked in the Shoulders lab under Michael Xiong, where she helped test for a technology that tags secretory pathway proteins for degradation. Sara aspires to pursue a PhD in Pharmacy and serve her country.
A PROTAC-Based Approach for targeted degradation of secretory pathway
proteins using CATCHFIRE
Sara Mia Cotto Ortiz¹, Michael Xiong², Dr. Matthew Shoulders²
¹Department of Chemistry, University of Puerto Rico, Rio Piedras Campus
²Department of Chemistry, Massachusetts Institute of Technology
The Endoplasmic Reticulum is an important organelle where secreted and lysosomal proteins pass through. These proteins can get misfolded and accumulate, causing various diseases. Targeted protein degradation technologies, such as PROTACs, have been created to combat these problems. However, none have been successful for ER proteins. As a solution, the lab proposed ERAD-TACs, a technology that uses a linker to bind OS9, a chaperone protein important in ER-associated degradation. In this project, we tested a new method for the design of ERAD-TACs using Chemically Assisted Tethering of a Chimera by Fluorogenic-Induced Recognition (CATCHFIRE). CATCHFIRE uses two amino acid chains, FIRE-tag and FIREmate, that, when bound with Match 550, emit fluorescence. We transfected HEK293 cells with a plasmid containing the CATCHFIRE components and OS9 and split them into 4 different conditions: no treatment, dox-promoter treatment, Match 550, and one with both. Comparison of the fluorescent signal between the third and fourth conditions confirmed that dimerization occurred. Through a Western blot, we hope to see if dimerization led to degradation of the FIRE-mate. Success will open a new form of targeted protein degradation in the ER, which will help prevent diseases that result from the failure of protein degradation
