A-Alpha Bio was founded in 2017 by a group of current and former synthetic biology doctorate students at the University of Washington Institute for Protein Design and Center for Synthetic Biology. Co-founder and CEO David Younger was mentored by Eric Klavins, the director of UW’s Center for Synthetic Biology and David Baker, head of the Institute for Protein Design. Klavins and Baker are now scientific advisers for A-Alpha Bio. The AlphaSeq platform was invented by Younger and co-founder and CTO Randolph Lopez. The company started out at UW’s CoMotion innovation hub.
A-Alpha Bio’s platform called AlphaSeq allows the assessment in parallel of a very large number of possible interactions between biomolecules in two large libraries. Interacting molecules and proteins work like keys and locks fitting together to turn on or off cellular processes. A-Alpha Bio’s system can search through millions of proteins at once looking for the right combination of key and lock which could function at a therapeutic level to block disease or boost the immune system.
The AlphaSeq platform technology measures protein interactions by quantifying interactions between cells displaying proteins on their surfaces. It uses engineered yeast cells to understand how drugs interact with different proteins. The technology helps pharmaceutical companies understand how potential drug candidates would operate inside a person's body, letting them rule out problematic drugs before they start clinical trials.
The technology used in their AlphaSeq system was described in PNAS in 2017. Yeast are reprogrammed so that the protein-protein interaction strength is linked to mating efficiency using synthetic agglutination (SynAg). Yeast mating in an aerated liquid culture depends on an intercellular protein-protein interaction which drives agglutination between MATa and MATalpha haploid cells. Wild-type agglutination proteins the normally interact for mating were replaced by synthetic agglutination (SynAg) proteins expressed on the cell surface. Interaction between the SynAg proteins can be quantitatively assessed coculturing the two haploid strains and measuring their mating efficiency. The approach was extended for library-on-library characterization of protein-protein interactions by barcoding SynAg gene cassettes. Many haploid yeast strains can be cocultured and next-generation sequencing used to count interaction frequencies for all possible MATa-MATalpha SynAg protein interactions.
In July 2018 the company announced it had won a $225,000 grant from the National Science Foundation (NSF). The funding brings the company's total funds raised to date to $410,000.
High-throughput characterization of protein-protein interactions by reprogramming yeast mating
Co-founder and CEO
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