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Protein Design Lab

Christopher Bahl

About the Protein Design Lab

We develop and leverage cutting-edge computational engineering methods to create proteins with novel function and capabilities. Our designed proteins have never been seen before in nature, and we use high-throughput automation technologies to make and test them in the laboratory. Our protein design technologies promise to deliver breakthrough therapeutics and deepen understanding of the molecular machines that drive nearly all of life’s chemical reactions.

Research Interest

The IPI Protein Design unites in silico and in vitro technologies to pursue three research interests.

Design of miniprotein binders de novo

Miniproteins are short chains of amino acids that can perform very specific functions. We engineer miniproteins via rational, structure-based design and construction/screening of diverse libraries using display technologies. Using and developing new approaches, we can rapidly create miniproteins that bind to a wide breadth of targets. We utilize our miniproteins to engage in collaborations with researchers in a broad array of fields including oncology, autoimmunity, diagnostics, infectious disease and agriculture.

Development of therapeutics to target G protein coupled receptors

G protein-coupled receptors (GPCRs) are a family of proteins that represent a critically important class of drug targets. More than a third of all medicines approved by the US Food and Drug Administration bind to GPCRs, which in turn signal vital body functions by interacting with G proteins in cells. We have successfully designed proteins de novo that mimic the GPCR binding site of a G protein. Our designed “G protein mimetics can bind to a broad array of GPCRs, and we are using them to simplify GPCR structure determination and accelerate the discovery of protein-based therapeutics.

Relationships between protein structure and behavior in solution

While the number of protein-based therapeutics in clinical trials is increasing, the process of producing and formulating lead protein molecules remains a significant challenge. Our solution is to partner with industry to gain insight into the intricate relationships between protein structure and behavior. Using IPI’s robotic platform, we are generating large quantities of high-quality data that is enabling machine learning to rationally control protein developability. The goal is to engender a new platform to enable faster clinical translation.

Expertise & Speciality

Computational de novo Protein Design

Proteins are incredibly powerful molecular devices that can solve many challenges in science and medicine. Traditionally, scientists have engineered proteins by repurposing or improving molecules discovered from nature. Now, advancements in computational modeling have enabled protein engineers to build macromolecules entirely from scratch, different from anything in the natural world. At IPI, we specialize in developing de novo protein design algorithms, which allow us to create these novel functional
proteins.

Automated High-throughput Laboratory Science

A common roadblock in protein engineering is a lack of diversity in proteins that can be produced and tested in the laboratory. To overcome this hurdle, we innovate new ways of producing and testing proteins involving liquid handling robotics. This approach yields substantial increases in throughput, which we leverage to generate large datasets of protein properties. Our goal is to apply machine learning and solve formerly unsolvable problems.

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