Hear from the Huang lab at Stanford University

Dr. Possu Huang's laboratory at Stanford University is focused on designing and testing novel protein structures using computational modeling, structural biology, and experimental library optimization.

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We build computational models of proteins based on design hypotheses. The fact that you can cover exactly the distribution, positions, and mutation sites to test our hypotheses, not only streamlines the experiments but also informs our understanding better than using degenerate codons.

- Possu Huang, Stanford University

Project’s Critical Challenge

Huang's team has developed various platforms for protein engineering, which can address obstacles in biomedical, industrial, and synthetic biology applications. The team has undertaken various protein bioengineering projects, including developing the TRACeR platform to design novel proteins with improved recognition of peptides presented in the context of MHC complexes.

Huang’s group was inspired by superantigens to develop novel TCR-like proteins that can specifically recognize MHC-bound peptides. These molecules can be used in various cancer immunotherapy strategies and potentially enhance CAR-T cells’ specificity.

Computational protein design pipelines enabled them to model interactions and identify suitable protein conformations for docking and binding to peptide-MHC complexes. The team then undertook high-throughput screening approaches, leveraging a yeast display library and peptide-loaded MHC tetramers to test their various protein designs.

However, evaluating many mutations resulting from random changes can significantly slow their progress in the screening stage. Therefore, Huang's team relied on GenScript's Precision Mutant Library services to address this challenge and build a library containing only the desired mutations representing select protein designs.