Results of the Protein Engineering Tournament: An Open Science Benchmark for Protein Modeling and Design.

The grand challenge of protein engineering is the development of computational models to characterize and generate protein sequences for arbitrary functions. Progress is limited by lack of (1) benchmarking opportunities, (2) large protein function datasets, and (3) access to experimental protein characterization. We introduce the Protein Engineering Tournament-a fully-remote competition designed to foster the development and evaluation of computational approaches in protein engineering.

Can protein expression be 'solved'?

Recombinant protein expression is central to biotechnology's application. However, not all proteins can be expressed in all organisms, and, given the vast experimental space, it can be challenging to identify the conditions that will yield successful protein expression. The field lacks a predictive model of soluble protein expression that could replace laborious experimental trial and error.

Custom CRISPR-Cas9 PAM variants via scalable engineering and machine learning.

Engineering and characterizing proteins can be time-consuming and cumbersome, motivating the development of generalist CRISPR-Cas enzymes to enable diverse genome-editing applications. However, such enzymes have caveats such as an increased risk of off-target editing. Here, to enable scalable reprogramming of Cas9 enzymes, we combined high-throughput protein engineering with machine learning to derive bespoke editors that are more uniquely suited to specific targets.

Continuous evolution of user-defined genes at 1 million times the genomic mutation rate.

When nature evolves a gene over eons at scale, it produces a diversity of homologous sequences with patterns of conservation and change that contain rich structural, functional, and historical information about the gene. However, natural gene diversity accumulates slowly and likely excludes large regions of functional sequence space, limiting the information that is encoded and extractable. We introduce upgraded orthogonal DNA replication (OrthoRep) systems that radically accelerate the evolution of chosen genes under selection in yeast.