Using naturally evolved phenotypic variation to decipher the positional regulatory code of mammalian skin

Information

  • Research Project
  • 10246985
  • ApplicationId
    10246985
  • Core Project Number
    R35GM133758
  • Full Project Number
    5R35GM133758-03
  • Serial Number
    133758
  • FOA Number
    PAR-17-190
  • Sub Project Id
  • Project Start Date
    9/13/2019 - 4 years ago
  • Project End Date
    8/31/2024 - 2 months from now
  • Program Officer Name
    HOODBHOY, TANYA
  • Budget Start Date
    9/1/2021 - 2 years ago
  • Budget End Date
    8/31/2022 - a year ago
  • Fiscal Year
    2021
  • Support Year
    03
  • Suffix
  • Award Notice Date
    8/31/2021 - 2 years ago
Organizations

Using naturally evolved phenotypic variation to decipher the positional regulatory code of mammalian skin

Project summary My proposed research seeks to uncover the precise developmental mechanisms by which gene regulatory complexity is translated through cellular behaviors into specific morphological outcomes. Achieving this constitutes a fundamental challenge in biomedical sciences, as errors in embryonic patterning often lead to congenital and postnatal abnormalities that can have The mammalian skin displays marked anatomical variation in growth, thickness, pigmentation, and types of cutaneous appendages. These regional differences arise during embryogenesis, suggesting that gene regulatory networks controlling skin development harbor a latent reservoir of anatomical complexity. To understand how such regulatory complexity is translated into spatial patterns of cellular differentiation, drastic consequences for individuals. my research program combines the study of diverse, naturally occurring phenotypes in emerging model species, with parallel studies in the laboratory mouse, where powerful molecular and genetic tools already exist. The proposed experiments seek to elucidate how the skin acquires, interprets, and executes positional information by focusing on two distinct spatially patterned phenomena during skin development (1) stripe pattern formation in rodents, using a system I established as a postdoc and (2) formation of gliding membranes in marsupials, using a system under development in my laboratory. The approaches described in the two research programs integrate multiple disciplines, including developmental biology, molecular biology, evolutionary genetics, and functional genomics, with my expertise in skin developmental biology (postdoctoral training) and demonstrated success developing molecular tools in emerging model species (graduate and postdoctoral training). By focusing on developmental mechanisms, this work will uncover the stepwise processes by which genetic information generates spatial patterns of cellular differentiation during embryogenesis, provide a comprehensive roadmap for linking genotype and phenotype at an unprecedented mechanistic and conceptual level, and will generate fundamental insights into the biology of mammalian skin, from the processes controlling skin development and homeostasis to the mechanistic bases of diseased states.

IC Name
NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
  • Activity
    R35
  • Administering IC
    GM
  • Application Type
    5
  • Direct Cost Amount
    249922
  • Indirect Cost Amount
    147008
  • Total Cost
    396930
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    859
  • Ed Inst. Type
    GRADUATE SCHOOLS
  • Funding ICs
    NIGMS:396930\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZGM1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    PRINCETON UNIVERSITY
  • Organization Department
    BIOCHEMISTRY
  • Organization DUNS
    002484665
  • Organization City
    PRINCETON
  • Organization State
    NJ
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    085430036
  • Organization District
    UNITED STATES