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An in vivo screen for genes underlying protective neonate respiratory reflexes to identify potential contributors to Sudden Infant Death Syndrome and other congenital respiratory pathophysiologies

Award Number: R01HL161142
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY ABSTRACT The goal of this proposal is to identify genes that are required for neuro-developmental and cellular processes critical to protective neonate respiratory reflexes that may be perturbed in Sudden Infant Death Syndrome (SIDS) and other congenital respiratory pathophysiologies. To that end, we are in a unique position to leverage the Baylor College of Medicine (BCM) Knockout Mouse Project-2 (KOMP2)/International Mouse Phenotyping Consortium (IMPC) efforts to knock out or mutate and characterize every gene in the mouse genome. The BCM KOMP2/IMPC effort is focused on adult as well as some embryonic and perinatal top-level phenotyping. However, this effort does not systematically or deeply evaluate adult or neonate respiration. Thus, we aim to leverage the BCM KOMP2/IMPS knockout production and phenotyping pipeline to identify genes critical to the development and function of neural networks in neonate respiration. The hypercapnic and hypoxic ventilatory reflexes are hypothesized to be perturbed in SIDS and several other congenital respiratory disorders. Failure of the neonate auto-resuscitation reflex is thought to be a common end point for many SIDS cases. Therefore across two aims, we propose to screen KOMP2 mutant mouse lines to identify novel genes involved in the development and function of protective neonate respiratory reflexes including 1) the hypercapnic and hypoxic ventilatory reflexes; 2) and the neonate auto-resuscitation reflex; 3) followed by an initial neuro-anatomical characterization of cellular, molecular and genetic markers in the mutants. To achieve the high throughput capacity and precision needed to screen sufficient numbers of mutant lines and gain meaningful results, we have developed a novel robotic closed loop automated neonate respiratory platform and data analysis pipeline. The proposed phenotyping pipeline will enable a multifaceted characterization of genes that when homozygously or heterozygously mutated, disrupt critical protective neonate respiratory reflexes. The successful outcomes will deliver a suite of genes that provide a foundation for additional studies to yield important clues about the genetic, molecular, cellular processes that underly respiratory neural network development and function in neonates as well as inform upon the mechanistic underpinnings of congenital pathophysiologies such as SIDS, CCHS, Rett Syndrome and others.


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: 2023 ( Subtotal = $702,842 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	National Center on Sleep Disorders Research	001	2	2/11/2023	NON-COMPETING CONTINUATION	$70,285
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	National Center on Sleep Disorders Research	000	2	11/25/2022	NON-COMPETING CONTINUATION	$632,557


Issue Date FY: 2022 ( Subtotal = $702,842 )
2022	2022	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	National Center on Sleep Disorders Research	000	1	11/23/2021	NEW	$702,842


Grand Total All Awards = $1,405,684

Sum of Action Amount is $1,405,684;

Grand Total = $1,405,684

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An in vivo screen for genes underlying protective neonate respiratory reflexes to identify potential contributors to Sudden Infant Death Syndrome and other congenital respiratory pathophysiologies

Award Number: R01HL161142

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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