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Engineering pathogen triggered biomineralization to enable a new generation of point-of-care tests

Award Number: R21AI152200
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT Biomineralization is a coalescence of organic (soft) and inorganic (hard) chemistries where proteins or peptides borne on a close-knit macromolecular scaffold serve as nucleation sites for salts to precipitate from solution and grow into crystals. When these proteins or peptide motifs are free in solution phase at low concentrations, biomineralization does not occur. We aim to harness this concentration dependent phenomenon to formulate a new generation of pathogen specific assays. Biomineralizing motifs will be fused to antibodies specific to macromolecular scaffolds of pathogens, so that the presence of pathogen will cluster the fusions, concentrating them to trigger crystal formation. The approach requires no washing steps and should give a visible readout in this feasibility study for an exploratory point-of-care assay. We will first isolate protein motifs capable of driving the formation of physiological buffer salt crystals from solutions. We will then employ Filovirus preparations and pre-existing antibodies against polyvalent viral cores to assess biomineralization potential of motif-antibody fusions and establish limits of detection (LOD) for Ebola and Marburg viruses to benchmark our system. Finally, we will engineer mutants of the motifs to understand drivers of biomineralization, accelerating the process, reducing assay times and lowering LOD. While initially meant as a point-of-care assay feasibility study, the process should also be addressable by conductivity measurements and imaging for biosensing applications. If successful, future developments could also include retuning the process to operate against adjacent nucleic acid sequence targets by fusing the biomineralizing motifs to oligonucleotide probes. Convenient and inexpensive diagnostics that don’t require vast infrastructure investment are desperately needed in the field, especially for emerging zoonoses in resource limited geographies. Our feasibility study will show whether biomineralization can contribute to solving this problem and offer a paradigm shifting parallel track for further development to help safeguard human health.


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 = $0 )
2024	2021	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	000	2	4/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	000	2	4/4/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $247,500 )
2021	2021	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	000	2	3/24/2021	NON-COMPETING CONTINUATION	$247,500
														Subtotal = $247,500

Issue Date FY: 2020 ( Subtotal = $297,000 )
2020	2020	TEXAS BIOMEDICAL RESEARCH INSTITUTE	8715 W MILITARY DR	SAN ANTONIO	TX	78227	BEXAR	USA	Allergy and Infectious Diseases Research	000	1	3/17/2020	NEW	$297,000
														Subtotal = $297,000

Grand Total All Awards = $544,500

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Engineering pathogen triggered biomineralization to enable a new generation of point-of-care tests

Award Number: R21AI152200

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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