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Causes and consequences of differential gene regulation in the development of alternate phenotypes

Award Number: F31HD118780
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: 04/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Causes and consequences of differential gene regulation in the development of alternate phenotypes - Abstract Complex multicellular organisms develop through hundreds of precisely orchestrated genetic interactions that can lead to deleterious phenotypes like disease when disrupted. Many genes require conservation in their expression to perform their specific functions and activities in concert with other genes. Yet, developmental programs and regulatory networks are frequently modified to produce beneficial, novel, or alternate phenotypes. The most obvious example of this is the evolution of adaptive sexual dimorphisms within and across species. This suggests a degree of flexibility in highly conserved developmental systems that can be accessed by genetic variation. However, the molecular mechanisms by which genetic variation relates to developmental pathway architecture remains poorly understood. A powerful and natural system in which to investigate this is phenotypic polymorphism, defined as the co-occurrence of multiple distinct phenotypes within a species. Alternate phenotypes, including adaptive polymorphisms and disease states, arise from distinct developmental programs that are shaped by underlying genetic variation, often at just one or a few genes. My proposed work aims to characterize the link between genetic variation and developmental variation by using a natural system of female- limited polymorphism in Papilio butterflies. In several species, the gene doublesex controls the development of female-limited wing pattern polymorphism. Ancestrally, doublesex (dsx) regulates sex differentiation by controlling the development of multiple secondary sexual traits across insects. In addition to performing its role in sexual differentiation, alternate dsx alleles cause females to develop either a derived mimetic or an ancestral non-mimetic color pattern. Both female forms co-occur, with males developing a single phenotype. My proposed work will uncover and experimentally test what mutation(s) caused dsx to be reused to control the color pattern development switch, and characterize the cis-regulatory architecture controlling allele-specific expression. Additionally, I will characterize how dsx integrates with or modifies the wing development program by identifying the direct targets of DSX and associated gene expression changes. Collectively, these experiments will tease apart genetic interactions underlying developmental program modifications at a novel level of precision. Moreover, by contrasting results from closely-related species with and without female-limited polymorphism, my proposed work will highlight the common and unique elements of wing development programs that have been modified by the insertion of the same reused gene. This will bear directly on our understanding of how shared genes and programs are (re)deployed across diverse genetic and genomic backgrounds to produce new phenotypes.


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	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Child Health and Human Development Extramural Research	000	1	2/10/2026	NEW	$49,538
2026	2026	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Child Health and Human Development Extramural Research	001	1	2/10/2026	NEW	$0
2026	2026	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Child Health and Human Development Extramural Research	002	1	4/3/2026	NEW	$576
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Causes and consequences of differential gene regulation in the development of alternate phenotypes

Award Number: F31HD118780

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: 04/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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