Thursday, November 21, 2024 11/21/2024

Design-driven engineering of robust mammalian sense-and-respond functions: from parts to programs

Award Number: R01EB026510
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary The overarching goal of this project is to enable the use of engineered cell therapies to safely and effectively treat conditions ranging across cancer, autoimmune disease, and regenerative medicine. Engineered cell therapies are an exciting frontier, with early successes in cancer treatment demonstrating the transformative potential of this approach. Customized cell therapies could yield safe and effective treatments for many applications beyond cancer, but realizing this potential is limited by the fact that evaluating a potential therapeutic strategy requires extensive time and resources to implement it. The goal of this project is to flip this paradigm— to enable spending less time building and thus focus on evaluating potentially useful strategies. This project will develop state-of-the-art technologies for cell engineering and enable their application to solve three open, complementary, clinically motivated challenges. The first aim is to develop the technology, understanding, and computational tools required to build genetic programs that employ natural mechanisms for implementing long-lived memory. Natural systems employ genetic memory to drive processes such as differentiation and development by adding and removing stable marks to the genome. Although research has yielded insights into how to drive such changes, bioengineers do not yet have the ability to leverage those insights to build programs that implement these effects for useful purposes. This project will address this need by developing genetic programs that exhibit stable behaviors including inducible and autonomous state switching. The second aim will generate novel candidate cell therapies for treating cancer that leverage foundational advances for engineering cells to evaluate and respond to external cues (e.g., unique markers of the tumor site) to induce desired therapeutic behaviors. This work will develop programs hypothesized to improve both safety and efficacy of these approaches. A key aspect of this work is employing model-guided design to evaluate and refine genetic programs to confer desired behaviors. The third aim will develop a computational framework enabling computer-assisted design of genetic programs. Current design is limited by the imagination of the designer—a human must propose a design which is subsequently evaluated. This aim will make the transformative leap to semi-automated design, establishing workflows and tools that are freely accessible to researchers in a graphics-enabled open software framework.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $580,634 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	6	4/30/2024	NON-COMPETING CONTINUATION	$580,634
2024	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	5	4/3/2024	COMPETING CONTINUATION	$41,746
2024	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	4/3/2024	NON-COMPETING CONTINUATION	-$39,734
2024	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	4/3/2024	SUPPLEMENT FOR EXPANSION	-$2,011
														Subtotal = $580,634

Issue Date FY: 2023 ( Subtotal = $615,361 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	5	6/22/2023	COMPETING CONTINUATION	$615,361
2023	2022	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	5/18/2023	NON-COMPETING CONTINUATION	$0
2023	2022	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	6/14/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $615,361

Issue Date FY: 2022 ( Subtotal = $363,963 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	5/25/2022	NON-COMPETING CONTINUATION	$346,428
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	12/9/2021	SUPPLEMENT FOR EXPANSION	$17,535
														Subtotal = $363,963

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	6/18/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $346,860 )
2020	2020	NORTHWESTERN UNIVERSITY	633 CLARK	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	5/5/2020	NON-COMPETING CONTINUATION	$346,860
														Subtotal = $346,860

Issue Date FY: 2019 ( Subtotal = $313,420 )
2019	2019	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	5/7/2019	NON-COMPETING CONTINUATION	$313,420
														Subtotal = $313,420

Issue Date FY: 2018 ( Subtotal = $313,811 )
2018	2018	NORTHWESTERN UNIVERSITY	633 CLARK ST EVANSTON	EVANSTON	IL	60208	COOK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	7/24/2018	NEW	$313,811
														Subtotal = $313,811

Grand Total All Awards = $2,534,049

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Design-driven engineering of robust mammalian sense-and-respond functions: from parts to programs

Award Number: R01EB026510

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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