Matthew McNulty
University of California, Davis
The NSTRF will offer me the freedom to explore the challenges of deep space travel that I would only otherwise imagine. I strive to realize sustainable life support systems for deep space travel from my novel perspective at the intersection of chemical engineering, plant biotechnology, and virology.
I aspire to work with together with NASA’s Center for Utilization of Biological Engineering in Space (CUBES) to realize a Mars full of life. One main aim of CUBES is to use plants to harness solar energy and in situ resources on Mars to produce food and pharmaceuticals for a human crew. I propose to contribute a new but synergistic aspect to this vision — to use the plant mass leftover from food and pharmaceutical production to generate a biologically-derived nanoparticle device capable of simply and sustainably purifying human pharmaceuticals on Mars. Pharmaceutical purification for human use is not currently simple nor sustainable, requiring many processing steps and chemical apparatus. The centerpiece of this proposed deep space purification technology is “making an ally from an enemy” — viewing plant viruses not as pests, but as versatile assets in the biomanufacturing toolbox. There are three stages of my proposed research. First, I will genetically engineer a plant virus to display proteins capable of binding to antibodies or Fc-fusion protein pharmaceuticals, which account for over 50% of all biopharmaceutical sales, and then produce high quantities of these virus-based immunosorbent nanoparticles (VINs) in inedible plant biomass. Second, I will take these VINs and immobilize them in a 3D bioprinted hydrogel membrane, which I aim to house in a simple 3D printed capsule with an inlet and outlet port. Impure pharmaceutical streams will enter the inlet and impurities will exit the outlet, leaving the pharmaceutical bound to the VINs on the hydrogel membrane. By inducing a mildly acidic environment, the pharmaceutical will lose binding affinity to the VINs and exit the outlet port, sufficiently pure for human injection. Third, I will optimize this technology for in situ resource constraints.
Key experimental methodologies include: 1) Agrobacterium-mediated infection and mechanical wound viral RNA infection as comparative methods for VIN production. 2) Transmission electron microscopy and gold-labeled antibodies to test that I have successfully produced functional VINs. 3) Cryo-electron microscopy to more closely investigate VIN binding capacity and stability limitations. 4) Gel electrophoresis and densitometry to perform mass balances to investigate VIN production level and antibody recovery losses. 5) Industry-standard pharmaceutical purification processing (e.g. tangential flow filtration, chromatography) as a comparative case to VIN purification. 6) Enzyme-linked immunosorbent assays to test activity loss in the pharmaceutical after VIN purification.