Research

Proteins: Natural processes, including defense against pathogens and disease, involve multiple protein domains, weak interactions that function cooperatively, geometrically optimized elements, etc. The spatial and quantitative aspects of such systems are tweaked during evolution to create defenses that do not resemble the simple molecules designed by humans. Our goal is to create complex therapeutic proteins that mimic natural systems but avoid unwanted off-target effects. We have developed novel computational design strategies towards this goal. Current disease targets include pancreatitis, ALS, pain and milk production in nursing mothers.

Sensing and on-demand delivery in human cells: Given our improved understanding of building complex gene expression networks, we now seek to introduce these back into cells to perform as more precise therapeutics with respect to timing, physiological state, etc. Towards this end, we are developing technologies for introducing large DNAs into human cells including a novel artificial chromosome.
Surviving extremes: We have developed new strategies for protecting bacteria, viruses and fungi from stress conditions such as drying and temperature changes. We use proteins from organisms such as tardigrades that can withstand extreme conditions. Together with colleagues at MIT, we have developed novel formulations that incorporate proteins. We seek to apply this strategy to therapeutic cells to try to reduce dependence on the cold chain. Together with collaborators from BU, we are using a new strategy to look for roles of these proteins in coral preservation.

Biology is remarkable at sensing and responding to molecules in the environment. We seek to use this power to develop living biosensors. These include detectors of harmful chemicals (such as PFAS) and signatures of pathogens. Our approach relies on protein design and makes extensive use of AI and evolution.

Existing biological systems are rarely evolved to produce pure compounds in large quantities. Instead, life evolved exquisite control over producing a wide range of chemical products. By interfacing inorganic catalysts with engineered bacteria, it may be possible to merge high yields with biology’s chemical catalog. To this end, we created the ‘bionic leaf’, a system in which the bacterium converts CO2 and H2 produced from electrolysis into commercially relevant molecules and biomass.
We have enhanced the process of rock weathering to enhance sequestration of carbon in the ocean and soil. By one approach, we engineered ocean bacteria to produce natural molecules that can sequester iron which would otherwise be inhibitory. We envision a role for these bacteria in soil enhancement. New approaches involve design of never-before-seen enzymes.