Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-020-18840-8
Keywords
-
Categories
Funding
- NIH Director's New Innovator Award [DP2HD091793]
- NCI [GR10003709]
- NSF GRFP
- National Institutes of Health GT BioMAT Training Grant [5T32EB006343]
- Georgia Tech President's Fellowship
- National Science Foundation Graduate Research Fellowship [DGE-1650044]
- Burroughs Welcome Fund
Ask authors/readers for more resources
Engineered biocircuits designed with biological components have the capacity to expand and augment living functions. Here we demonstrate that proteases can be integrated into digital or analog biocircuits to process biological information. We first construct peptide-caged liposomes that treat protease activity as two-valued (i.e., signal is 0 or 1) operations to construct the biological equivalent of Boolean logic gates, comparators and analog-to-digital converters. We use these modules to assemble a cell-free biocircuit that can combine with bacteria-containing blood, quantify bacteria burden, and then calculate and unlock a selective drug dose. By contrast, we treat protease activity as multi-valued (i.e., signal is between 0 and 1) by controlling the degree to which a pool of enzymes is shared between two target substrates. We perform operations on these analog values by manipulating substrate concentrations and combine these operations to solve the mathematical problem Learning Parity with Noise (LPN). These results show that protease activity can be used to process biological information by binary Boolean logic, or as multi-valued analog signals under conditions where substrate resources are shared. In contrast to genetic circuits, here the authors develop protein biocircuits based on proteases. They show these activity-based circuits can execute Boolean logic for programmable drug delivery and perform fuzzy logic to solve a mathematical oracle problem, Learning Parity with Noise.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available