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Regulation of tissue mechanics in morphogenesis by PI4-Kinase Fwd

Award Number: F31HD123631
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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Regulation of tissue mechanics in morphogenesis by PI4-Kinase Fwd - PROJECT SUMMARY/ABSTRACT Embryonic lethality and congenital birth defects often arise from defects in morphogenesis, particularly disruptions in epithelial tissue remodeling. Epithelial folding, the bending of an epithelial sheet into a furrow or tube, is a critical mechanism for building 3D tissue architectures. Ventral furrow (VF) formation during Drosophila gastrulation provides an excellent model for epithelial folding. During VF formation, cell shape changes that drive invagination require cells to rapidly expand their surface area in response to mechanical forces, despite the inherent inelasticity of the plasma membrane, which can rupture when modestly overstretched. How cells expand their surface to support these dynamic shape changes remains poorly understood. Our lab has identified Four Wheel Drive (Fwd), a phosphatidylinositol 4-kinase IIIβ ortholog, as a key regulator of cell surface expansion during VF formation, offering a unique entry point into this question. This proposal aims to uncover how cells coordinate membrane growth with morphogenetic forces to regulate surface expandability, and how this subcellular property influences tissue-scale morphogenesis. Based on preliminary data, I hypothesize that Fwd supports cell surface expansion through PI(4)P and Rab11-dependent Golgi-to-plasma membrane trafficking, thereby modulating cell surface expandability to enable dynamic cell shape changes. I further propose that alteration in cell surface expandability will not only influence the passive mechanical properties but also impact the mechano-sensitive organization of the actomyosin-based force- generating machinery. I will combine Drosophila genetics with quantitative live imaging, optogenetics, biophysical measurements, and mathematical modeling to dissect Fwd-mediated surface expansion and its impact on tissue mechanics and morphogenesis. By investigating Fwd’s role in a well-characterized morphogenetic process, my work will (1) visualize intracellular trafficking during dynamic remodeling, (2) identify additional regulators of force-induced surface expansion, (3) link subcellular surface-expandability to tissue- scale mechanics, and (4) define how tissue mechanics shape the force-generating machinery. These studies will yield new insights into how mechanical inputs regulate cell behavior during morphogenesis. This three-year research project will also produce two publications: one on the molecular role of Fwd and another on the tissue- scale impact of defective surface expansion. The fellowship training plan will support my development as an independent researcher through long-term experimental planning, technical and scientific skill building, and expanded communication and mentoring abilities. Dartmouth College provides an exceptional environment for this work, offering broad research expertise, extensive core facilities, and a strong imaging core with advanced microscopes relevant to my proposal.


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: 2026 ( Subtotal = $50,114 )
2026	2026	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Child Health and Human Development Extramural Research	002	1	8/28/2026	NEW	$0
2026	2026	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Child Health and Human Development Extramural Research	001	1	8/24/2026	NEW	$0
2026	2026	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Child Health and Human Development Extramural Research	000	1	8/24/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Regulation of tissue mechanics in morphogenesis by PI4-Kinase Fwd

Award Number: F31HD123631

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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