Why start with yeast?
Yeasts are uniquely valuable microbes. Not only have they proved to be simple and resource-efficient discovery systems in academic research, but yeast are also widespread in industrial applications thanks to early adoption and domestication circa 1600. Since their industrial domestication, yeast have become critical factories for the production of fermented foods and beverage, nutritional products and extracts, biofuels, bulk and specialty chemicals, and even pharmaceuticals.
Despite the current industrial use, there is an unmet need for new purpose-optimized and task-specific yeast. As a product of rational-design and biological engineering, such yeasts can revolutionize industry by providing solutions to challenges in functionality, sustainability, and quality.
However, the power to realize yeast's potential is currently limited by the speed at which we can exploit their biology. The Make with Microbes project aims to accelerate our ability to exploit biology to solve human problems. We intend to build, from first principles, the world's most resource-efficient bio-expansion, bio-screening, bio-selection, and bio-manufacturing tools.
Biology at your service.
The ability to create new gene combinations is fundamental to developing new yeasts with rationally-designed functionality. Yeast mating is an extremely powerful but slow way to recombine pieces of genomes together. We intend to overcome this in three ways. Firstly, by developing new applications in yeast mating for existing high-throughput array-based and fluidic platforms. Secondly, by developing new high-throughput technologies that exceed the capacity of those currently available. Finally, by identifying shortcuts (in the form of mutants, hybrids, and chimerics) that make it possible to make more combinations in less time and with fewer resources.
Although we understand a tremendous amount about certain yeasts, this understanding applies only to a small fraction of the yeast biodiversity we have access to. To develop new yeasts with rationally-designed functionality, it is crucial that we expand upon available genotype and phenotype data. We aim to characterize thousands of new yeast strains/species. From this, we intend to create a densely connected graph and expect to discover new ways that microbes can be exploited to solve real-world problems. To do this at the high volumes required to make this project successful we need to develop new applications on top of existing technologies. We will also need to test new custom screening platforms that miniaturize existing technologies and develop new analytical methods that leverage machine learning and that scale to the new volumes of data.
Selection & Manufacturing
To rationally-design, improve and evolve new functions for microbes, essentially building exactly what you want, to solve problems, we need powerful selection tools. Often, sufficiently diverse and/or robust selection tools do not exist, thus lengthening development time and making it extremely difficult to improve an important cellular function without breaking another. To enable the holistic engineering of microbes, we intend to develop new ways to measure and control the output of multiple cellular functions in parallel. We will do this by proving out scalable biosensor technology on important applications. We will extend this work by building automated systems that enable a higher throughout than is currently possible.
Interested? Come work with us.