FINAL PROJECT

A WHOLE-CELL COVID-19 BIOSENSOR

So... I decided to work on the initial high-level idea I proposed for COVID-19 detection during the genome engineering week I have written a whole grant proposal but below there is a high-level summary of the project. For detailed information please reach out! at bvicente@mit.edu

Massive point-of-care and at-home testing technologies are necessary to combat SARS-CoV-2 and future unknown pandemics. However, the real-time, broad and cheap detection of SARS-CoV-2 and other coronavirus remains a big challenge. The virus stays in the lower pulmonary tract and high viral load is required to ensure detection of viral RNA. RNA-based tests like PCR or antibodies are expensive and imply complex manufacturing, usually require highly trained personnel and show high variability in the sensitivity.

Synthetic biology, through whole-cell biosensors - ie. cells that recognize the virus a produce a reporter compound in return, like a color - can be a powerful tool to address these issues. In recent years, several studies have genetically programmed microorganisms to act as biosensors, and that's why I propose the design of a whole-cell biosensor for SARS-CoV-2 as a means to create a new platform for early and real-time viral detection.

The main goals of the project are detailed in the following figure:

The idea is to design a hybrid receptor formed by the domain in ACE2 - the SARS-CoV-2 receptor - that binds the virus and fuse it with an intracellular signal transduction domain based on engineered histidine-kinase two component systems (TCS).

We will integrate the receptor with a reporter genetic circuit that propagates the signal through the cell population via cell-cell communication mediated by quorum sensing (QS) and produces a second signal that maintains the reporter ON through a bistable toggle switch with a responder and a memory element. This approach will highly decrease the time to response and the viral load required for detection, given that all cells will respond regardless of whether they all bind SARS-CoV-2 or not.

Finally, we will design a point-of-care microfluidic device with capacity for multiple samples. This device will have the capacity for at-home testing, since it will provide the necessary controlled conditions for a whole-cell biosensor and an easy to use mechanism that does not require tubing or external pumping systems.