DESIGN OF ROBUST AND ACCURATE BIOSENSING SYSTEMS IN LIVING CELLS
Abstract
Engineering biology promises revolutionary changes to the way we approach problems in areas ranging from energy and environment to health and medicine. In particular, engineering cells to concurrently sense multiple molecular species and compute a response based on these is going to be critical in a number of applications, including biosignature classification. In this project, we focus on the design of robust and accurate multi-input biosensors that compute the ratio between the levels of different molecular species (Aim 1). Despite tremendous progress in sensor design, capabilities for tracking the ratios of multiple biomarkers in a simple and deployable format have not been realized. Yet, ratiometric biomarker signatures carry key information about stress, fatigue, and cognitive overload in challenging environments. Additionally, although today we can, in principle, build complex genetic circuits comprising multiple genes, loads that genes apply to the cellular host couple independently regulated genes. This complicates design and makes the behavior of any genetic device, and of biosensors in particular, fragile and inaccurate. We thus propose to develop widely applicable tools, grounded on control theoretic concepts, to decouple the expression of independently expressed genes from each other (Aim 2). This should result in more accurate and predictable performance of engineered biosensors and genetic circuits more generally. Finally, we propose to determine the effects of intracellular spatial heterogeneity on sensor performance and to provide theory-grounded guidelines on how to optimize sensor design exploiting spatial effects (Aim 3).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 12, 2021
- Source ID
- FA95502010044
Entities
People
- Domitilla Del Vecchio
Organizations
- Air Force Office of Scientific Research
- Massachusetts Institute of Technology
- United States Air Force