Using Established Leptin Signaling Mutants to Study Cell Physiology and Bone Development in Zebrafish

Information

  • Research Project
  • 10114644
  • ApplicationId
    10114644
  • Core Project Number
    R15DK124790
  • Full Project Number
    1R15DK124790-01A1
  • Serial Number
    124790
  • FOA Number
    PAR-18-714
  • Sub Project Id
  • Project Start Date
    4/19/2021 - 3 years ago
  • Project End Date
    4/18/2024 - a month ago
  • Program Officer Name
    ZAGHLOUL, NORANN
  • Budget Start Date
    4/19/2021 - 3 years ago
  • Budget End Date
    4/18/2024 - a month ago
  • Fiscal Year
    2021
  • Support Year
    01
  • Suffix
    A1
  • Award Notice Date
    4/19/2021 - 3 years ago
Organizations

Using Established Leptin Signaling Mutants to Study Cell Physiology and Bone Development in Zebrafish

The proposed research is centered on understanding the hormone leptin's effects on bone. Leptin is a circulating protein hormone primarily known for its role in appetite control and fat deposition in mammals. Leptin also has many other effects, including influencing sexual maturity, the immune system, and bone metabolism. Even after hundreds of studies in mammals, there is not a consensus as to whether leptin's effects on bone increase or decrease bone volume. The comparative method, wherein organisms are compared with humans to understand similarities and differences among them, has paid great health dividends throughout the history of medicine (e.g. neuroscience using the squid axon, excretion using the shark rectal gland, and genetics using fruit flies). This proposal proposes to apply the comparative method by using zebrafish to help resolve the conflicting results of leptin bone studies in mice. We propose to use established knockout mutants of leptin and other proteins in its signaling pathway (mmp9 and endospanin) in zebrafish (Danio rerio). We will test the hypothesis that bone volume changes are a function of leptin sensitivity, and that this sensitivity can be manipulated with the protein endospanin. This proposal will address two Aims; Aim I manipulates leptin sensitivity in embryos, and Aim II manipulates leptin sensitivity in adults (documenting differences between males and females, and response under high fat diet). The proposal will be conducted at an institution and a laboratory that is dedicated to high quality research experiences for its undergraduates. Both PIs have a extensive experience as mentors and have trained many currently practicing health science researchers and physicians.

IC Name
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
  • Activity
    R15
  • Administering IC
    DK
  • Application Type
    1
  • Direct Cost Amount
    300586
  • Indirect Cost Amount
    143319
  • Total Cost
    443905
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    847
  • Ed Inst. Type
    SCHOOLS OF ARTS AND SCIENCES
  • Funding ICs
    NIDDK:443905\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    MCE
  • Study Section Name
    Molecular and Cellular Endocrinology Study Section
  • Organization Name
    UNIVERSITY OF AKRON
  • Organization Department
    BIOLOGY
  • Organization DUNS
    045207552
  • Organization City
    AKRON
  • Organization State
    OH
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    443250001
  • Organization District
    UNITED STATES