RUI: Evolutionary Origins of BACE1 and Amyloid-Beta

Information

  • NSF Award
  • 1817867
Owner
  • Award Id
    1817867
  • Award Effective Date
    7/15/2018 - 7 years ago
  • Award Expiration Date
    6/30/2021 - 4 years ago
  • Award Amount
    $ 444,941.00
  • Award Instrument
    Standard Grant

RUI: Evolutionary Origins of BACE1 and Amyloid-Beta

This work examines the evolution of two proteins that are widely distributed in metazoan animals and underlie Alzheimer's disease (AD) in humans - the beta-secretase enzyme (BACE1) and the amyloid beta (A-beta) sequence. The main goal is to understand when and how protein molecules evolve new functions over time. Broader outcomes of this work include expanded access to STEM research for underrepresented minorities and first generation undergraduate students, and outreach to the broader community via a high school teaching module and a popular science article. <br/><br/>Gene duplications are believed to be major facilitators of the evolution of novel protein function. BACE1 evolved from a gene duplication event just after the origin of animals. At a later but as yet unknown point in time, an APP gene duplicate evolved a novel BACE1 substrate motif (A-beta). This project traces back the functional evolutionary history of the origin and interaction of these molecules and resolves, to the most precise degree possible, when BACE1 and APP/A-beta evolved. Two specific aims make up this research: (1) determining the functional origin of BACE1 activity, via a cell culture-based functional test and ELISA, to investigate which species retain BACE1 enzymatic activity, and (2) determining the functional origin of the APP beta cleavage site to determine which taxa retain bona fide BACE1 substrates, using a cell culture-based functional test and mass spectrometry.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

  • Program Officer
    Arcady Mushegian
  • Min Amd Letter Date
    7/18/2018 - 7 years ago
  • Max Amd Letter Date
    7/18/2018 - 7 years ago
  • ARRA Amount

Institutions

  • Name
    Kalamazoo College
  • City
    Kalamazoo
  • State
    MI
  • Country
    United States
  • Address
    1200 Academy Street
  • Postal Code
    490063291
  • Phone Number
    2693377162

Investigators

  • First Name
    Blaine
  • Last Name
    Moore
  • Email Address
    bmoore@kzoo.edu
  • Start Date
    7/18/2018 12:00:00 AM
  • First Name
    James
  • Last Name
    Langeland
  • Email Address
    lange@kzoo.edu
  • Start Date
    7/18/2018 12:00:00 AM

Program Element

  • Text
    Genetic Mechanisms
  • Code
    1112

Program Reference

  • Text
    NANOSCALE BIO CORE
  • Code
    7465
  • Text
    UNDERGRADUATE EDUCATION
  • Code
    9178
  • Text
    RES IN UNDERGRAD INST-RESEARCH
  • Code
    9229