NSF Org:	EF Emerging Frontiers
Recipient:	GEORGIA TECH RESEARCH CORP
Initial Amendment Date:	August 7, 2023
Latest Amendment Date:	August 7, 2023
Award Number:	2319391
Award Instrument:	Standard Grant
Program Manager:	Angel Garcia aegarcia@nsf.gov  (703)292-8897 EF  Emerging Frontiers BIO  Directorate for Biological Sciences
Start Date:	August 15, 2023
End Date:	July 31, 2027 (Estimated)
Total Intended Award Amount:	$2,225,964.00
Total Awarded Amount to Date:	$2,225,964.00
Funds Obligated to Date:	FY 2023 = $2,225,964.00
History of Investigator:	Mark Styczynski (Principal Investigator) Mark.Styczynski@chbe.gatech.edu Shuichi Takayama (Co-Principal Investigator) Brian Hammer (Co-Principal Investigator) Neha Garg (Co-Principal Investigator)
Recipient Sponsored Research Office:	Georgia Tech Research Corporation 926 DALNEY ST NW ATLANTA GA  US  30318-6395 (404)894-4819
Sponsor Congressional District:	05
Primary Place of Performance:	Georgia Institute of Technology 225 North Avenue, NW ATLANTA GA  US  30333-0002
Primary Place of Performance Congressional District:	05
Unique Entity Identifier (UEI):	EMW9FC8J3HN4
Parent UEI:	EMW9FC8J3HN4
NSF Program(s):	URoL-Understanding the Rules o
Primary Program Source:	01002324DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s):	068Z
Program Element Code(s):	106Y00
Award Agency Code:	4900
Fund Agency Code:	4900
Assistance Listing Number(s):	47.074

ABSTRACT

This project will create a tool that can be used by untrained users and without sophisticated equipment to allow diagnosis of medical conditions characterized by the combination of multiple indicator molecules. While some medical conditions can be diagnosed by the level of just a single molecule, most require the measurement of multiple molecules? levels to enable accurate diagnosis. To address this challenge in a user-friendly manner, this project entails creating a tool that harnesses biology to sense target molecules, combine the information gained from those measurements, and report out patient status to the user. The project uses technology that allows genes to be turned on and off in small droplets that mimic simplified versions of cells. Individual droplets sense an individual molecule and then communicate with another droplet that produces a combined readout. By having each droplet detect a single molecule and exploit a reusable form of communication with other droplets, it makes the tool modular for creation of diagnostics for essentially any set of target molecules. The droplet technology and the combination of proposed approaches for communication and combination of signals are unique and novel. If successfully completed, this project would impact society broadly and help address health and other inequities by enabling assessment and monitoring of nutrition status in developing countries and around the world, helping individuals and improving public health policy.

As a proof of principle testbed, the project focuses on the development of a comprehensive diagnostic for zinc deficiency, a condition that is responsible for the deaths of tens of thousands of children under the age of 5 every year. The droplet technology uses aqueous two-phase systems combined with cell-free transcription and translation to create ?protocells? that enable the implementation of biological circuits for sensing and signal integration and thus the creation of complex biosensors. Multiple protocells each produce a distinct messenger molecule drawn from nature to enable communication with a separate ?receiver? protocell that integrates the signal via a three-hybrid system. By using a common communication and integration framework, individual sensor protocells can be changed to sense different target molecules without impacting the downstream biological computation, which greatly simplifies the creation of new diagnostics for different conditions. An important part of the project will also include efforts to make the protocell platform more efficient and robust for field use. These efforts use the Rules of Life for Building a Synthetic Cell and for Microbiome Interactions and Mechanisms as the basis for the development of a platform that could have a substantial impact on nutritional epidemiology and patient health by virtue of easier access to medical diagnostics. The project also envisions and will entail pursuit of environmental applications of the proposed platform. These efforts, combined with outreach efforts and support for students from groups that are underrepresented in engineering, are expected to have a truly broad impact.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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