NIH Research Grant Awarded to Study Metabolism During Tissue Development

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Adam Paré, assistant professor of biological sciences.

Adam Paré, assistant professor of biological sciences in the Fulbright College of Arts and Sciences, has recently been awarded a $1.55 million NIH R01 grant, titled "Control of epithelial morphology and bioenergetics by Toll Receptors during dynamic tissue remodeling." This prestigious award will provide five years of independent research funding in support of Dr. Paré's work.

"I am very excited and honored to have received this significant R01 grant from the National Institutes of Health, which is the first grant of its kind awarded to a lab in the Department of Biological Sciences in many years," said Paré. "This award will be the backbone of our research group for at least the next 5 years, and it will allow us to continue our studies into underexplored connections between tissue remodeling and cellular metabolism during development. This work will give us a better understanding of how groups of cells dynamically rearrange to form complex tissues, and we believe it could also shed light on the underlying causes of certain birth defects, cancer metastasis, and impaired wound healing."

The Paré Lab uses fruit fly embryos as a model system to study how large groups of cells reorganize during development. Fruit fly embryos are much simpler and easier to manipulate than vertebrate embryos, but they possess nearly all the same types of genes as humans, meaning lessons learned in the fly are generally applicable across the animal kingdom.

Previous work by Paré uncovered a new role for a well-known family of proteins known as Toll receptors in controlling cell shape during elongation of the head-to-tail axis--which involves thousands of cells simultaneously changing shape to drive tissue extension. This was a surprising finding at the time, as Toll receptors had primarily been studied in the context of the immune system, where they act as a first line of defense against pathogens and foreign molecules. It turns out that cells can sense differences in the levels of their own Toll receptors relative to their immediate neighbors, and they can use this information to modulate cell tension and adhesion to change shape in genetically predetermined ways.

Paré hypothesizes that such dramatic tissue reorganization events should also require significant changes in metabolic energy usage, although these kinds of questions have been difficult to address in living organisms. This R01 award will fund novel genetic and microscopy-based approaches to address how signaling by Toll receptors and mitochondrial networks interact to drive cell shape change during axis elongation — revealing how biomechanics and bioenergetics are coordinately regulated during embryonic development.

Paré said, "There are also many intriguing links between Toll receptors and mitochondria during wound healing, cancer metastasis, and inflammation, and these studies could give us a better understanding of how altered cell shape and cellular metabolism affect damaged and diseased tissues."

Paré was one of four research project leaders in the Arkansas Integrative Metabolic Research Center, and the receipt of this award has allowed him to graduate from the AIMRC project leader program. The AIMRC was established in 2021 under an NIH Centers of Biomedical Research Excellence award led by Kyle Quinn, professor of biomedical engineering in the College of Engineering. The goal of the AIMRC is to understand the role of cell and tissue metabolism in disease, development, and repair, and the center has established research cores in bioenergetics, imaging and spectroscopy, and data science.  The AIMRC combines technical expertise and access to advanced equipment in these core areas with a cross-disciplinary faculty development and mentoring program designed to grow a critical mass of independent researchers with federally funded research programs related to metabolism.

The work funded by Paré's R01 grant will be a continuation of research he began with funding support from the AIMRC beginning in 2021. 

"My involvement in the AIMRC has been greatly beneficial to my career for numerous reasons, and I know it directly contributed to my success in obtaining this R01 grant," said Paré. "First, the AIMRC gave our lab stable funding for the last three years, which is absolutely critical for a new research group. Second, working on the initial proposal for the AIMRC catalyzed completely new avenues of scientific investigation for our lab, and we are currently in active collaborations with AIMRC director, Dr. Kyle Quinn, as well as the AIMRC Imaging and Bioenergetics Cores to combine our expertise in embryology with their expertise in measuring cellular metabolism."

Mentoring in technical scientific skills, grantsmanship, and the development of research products is also a key component of AIMRC support provided to new faculty by a team of senior faculty mentors and an External Advisory Board.

Paré explained, "The guidance provided by AIMRC Director Kyle Quinn and my other senior mentors in the center was critical for drafting and revising this R01 proposal. I am excited to graduate from my role as project leader to serve as a mentor in the AIMRC, and I hope I can pass on what I've learned about science communication and tailoring proposals to fit within the larger mission of the NIH to new project leaders in the center."

For more information on becoming an AIMRC Project Leader, or for other AIMRC funding opportunities, please visit the center website at aimrc.uark.edu or contact Kimberley Fuller at fullerk@uark.edu.