Homework

Week 1 HW: Principles and Practices
Biological Engineering Application I am developing a computational design pipeline to miniaturize enzymes, specifically to find the shortest amino acid sequence that retains a functional fold. This builds on the work that I do as a part of my PhD, specifically the protein design pipeline also known as BAGEL (see published paper and github repo). For this course, I want to experimentally test the pipeline on VioA, a tryptophan oxidase in the violacein pathway. Violacein is purple, so this assay readout is very trivial, and will be beneficial to validate my computational approach. Down the line, the long-term target is Cas9. At over 1,300 residues, SpCas9 is a large protein, difficult to fit into AAV vectors, making it a real bottleneck for practical use in gene therapy. If I validate my approach with VioA, I would be more confident in pursuing this further in a therapeutics context to find mini-Cas9 variants.