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 safe, regulated genetic networks that can be used in gene therapy to deliver therapeutic proteins on-demand.

    Reversible slowing of biological processes: It is a challenge to develop a therapeutic molecule that slows or pauses metabolism and prevents cellular damage. However, such a molecule would be invaluable for traumatic injury and the preservation of therapeutics, tissues and organs for transplant, and plants and living materials.  Intrinsically disordered proteins (IDPs) from organisms such as resurrection plants (time lapse below) hold promise for their ability to protect cells from severe environmental exposures. We are using IDPs as a starting point to learn how to design proteins for efficacy and safety.

  • Living sensors: Low-cost testing of samples for pathogenic nucleic acids is key to the detection and monitoring of pathogens in environmental samples. We are developing a colorimetric detection system in which crude wastewater is mixed with detector bacteria. One advantage of our system is that cell-based biosensors are robust to contaminants and can detect DNA in crude, unprocessed samples.

  • Designing around carbon capture: 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 are interested in using this to tackle useful chemical transformations.