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Quantifying the impact of hyperglycemia on embryonic metabolism and development in C. elegans.

Award Number: R21HD117015
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Quantifying the impact of hyperglycemia on embryonic metabolism and development in C. elegans. - PROJECT SUMMARY The objective of this project is to generate single cell resolution information about how metabolism changes at single cell resolution over the course of embryonic development in embryos from normal and hyperglycemic mothers. This is relevant to understanding why structural birth defects are 2-3 times more likely in pregnancies of diabetic mothers. We will use the nematode C. elegans as a model in our studies and since many aspects of development and metabolism are conserved, our findings will likely further our understanding how metabolism affects morphogenesis in vertebrate embryonic development and human structural birth defects. C. elegans is an excellent model because its simplicity and accessibility will enable us to fully characterize the cellular metabolism of individual cells during embryonic development and determine how hyperglycemia impacts cell fate specification and morphogenesis. Our preliminary data show that cellular metabolism varies across cells and across developmental time. We hypothesize that maternal hyperglycemia increases oxidative stress in embryonic cells, resulting in insufficient cellular energy for essential migrations and inducing AMPK-mediated chromatin changes that inhibit the expression of cell fate TFs, resulting in developmental defects. To test this hypothesis, we will use complimentary approaches of quantitative time-lapse imaging of biosensors, and transcriptomics plus metabolic modeling. We will integrate the results from each approach to create a single cell resolution profile of embryonic metabolism across developmental time in control and maternal hyperglycemia embryos. This will enable us to link developmental defects to disruptions in metabolism at the cellular level. This work will generate the first comprehensive metabolic atlas of a metazoan embryo with the single cell resolution across developmental time and determine how embryonic cellular metabolism and developmental processes are impacted by hyperglycemia.


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: 2025 ( Subtotal = $474,878 )
2025	2025	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Child Health and Human Development Extramural Research	000	1	7/18/2025	NEW	$474,878
														Subtotal = $474,878

Grand Total All Awards = $474,878

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Quantifying the impact of hyperglycemia on embryonic metabolism and development in C. elegans.

Award Number: R21HD117015

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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