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PPiSeq: High-Throughput Protein-Protein Interaction Sequencing

Award Number: R01AI164530
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/16/2015
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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PPiSeq: High-Throughput Protein-Protein Interaction Sequencing - Project Summary/Abstract Emerging and endemic viral pathogens are a persistent threat to human health, the global economy, and national readiness. Viral proteins interact with host proteins to hijack host cells and replicate transmissible viral particles. Human-viral and viral-viral protein-protein interactions (PPls) have been comprehensively characterized for a limited set of viruses, identifying a PPI profile for each virus screened. However, these efforts have characterized only a small fraction of the known viruses. A complete viral-human PPI map would be an invaluable resource, enabling analyses of how often interacting viral proteins converge on common human protein targets, cellular functions, or pathways, and which of these interactions are associated with transmissibility or virulence. Combining the viral-human PPI map with human population genetic analyses will enable characterization of the molecular mechanisms underlying extant and ancient epidemics and how these PPIs drive much of human adaptation. In addition, PPI profiles of human viruses could be used to aid screening of animal reservoirs to identify potential threats before a zoonotic spillover occurs. Despite its great promise, characterization of the viral-human PPI map remains a challenge given the throughput of current viral-human PPI screening assays. Current high-throughput assays also lack a quantitative output, meaning that the emergent human-viral PPI map, or viral-viral PPI maps, would be difficult to exploit for important downstream variant scanning or drug screening applications. Here we will use a quantitative sequencing-based protein-protein interaction assay platform to screen for PPls between -24 million viral-human or viral-viral protein pairs. We will further develop this technology into a massively parallel drug screening platform and use it to screen >3 million drug-PPI combinations for small-molecule compounds that promote or antagonize a PPI. The viral-human PPI and drug-PPI maps developed here will be an invaluable resource for a broad research community. In addition, this work will establish new massively parallel and quantitative PPI and drug-PPI screening technologies that will scale with advances in gene synthesis, mutagenesis and sequencing, enabling parallel screening of tens of thousands of gene and gene variants of extant, emerging, and potentially zoonotic viruses.


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 = $414,751 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	8	6/18/2024	NON-COMPETING CONTINUATION	$414,751
														Subtotal = $414,751

Issue Date FY: 2023 ( Subtotal = $411,632 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	001	7	9/13/2023	NON-COMPETING CONTINUATION	$0
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	7	6/6/2023	NON-COMPETING CONTINUATION	$411,632
														Subtotal = $411,632

Issue Date FY: 2022 ( Subtotal = $418,944 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	6	6/24/2022	NON-COMPETING CONTINUATION	$418,944
														Subtotal = $418,944

Issue Date FY: 2021 ( Subtotal = $416,937 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Allergy and Infectious Diseases Research	000	5	7/12/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$416,937
														Subtotal = $416,937

Grand Total All Awards = $1,662,264

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PPiSeq: High-Throughput Protein-Protein Interaction Sequencing

Award Number: R01AI164530

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/16/2015

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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