Project Grant R00HL168224

Award Date 7/15/24
Completion Date 6/30/27
Dollars Obligated $677K
Federal Grant Program
93.837
Assistance Type
Project Grant
Place of Performance
Pennsylvania, USA
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This Project Grant award from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837) supports research to optimize a carbon monoxide (CO)-sensing hemoprotein for use as an antidote for CO poisoning and a biosensor for CO detection in living cells. The $676,629.27 award to Wayne State University will fund a 3-year project with the following objectives:

  1. Utilize in vitro spectroscopic methods to identify the minimum functional subunit and key amino acid residues that confer high CO affinity, selectivity, and heme stability in a bacterial CO-sensing hemoprotein domain.

  2. Evaluate the safety and efficacy of the optimized hemoprotein truncates in vivo, assessing their ability to scavenge CO, reverse hemodynamic collapse, and prevent death in a mouse model of severe CO poisoning.

  3. Design a genetically encoded, CO-selective fluorescent reporter based on the CO-sensing function of the hemoprotein, characterize its CO-dependent response in vitro, and incorporate it into the mouse genome to quantify CO accumulation and define regimes for CO signaling, cytoprotection, and toxicity.

The outcomes from this project are expected to provide fundamental insights into hemoprotein ligand selectivity and demonstrate the therapeutic potential of the recombinant hemoprotein as a treatment for acute CO poisoning, while also enabling the development of critical biomolecular tools to elucidate CO-dependent signaling mechanisms relevant to human health.

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