Fusion of nanomagnetic and viral tools to interrogate brain-body circuits

Information

  • Research Project
  • 10261671
  • ApplicationId
    10261671
  • Core Project Number
    DP1AT011991
  • Full Project Number
    1DP1AT011991-01
  • Serial Number
    011991
  • FOA Number
    RFA-RM-20-011
  • Sub Project Id
  • Project Start Date
    9/30/2021 - 4 years ago
  • Project End Date
    7/31/2026 - 9 months from now
  • Program Officer Name
    CHEN, WEN G
  • Budget Start Date
    9/30/2021 - 4 years ago
  • Budget End Date
    7/31/2022 - 3 years ago
  • Fiscal Year
    2021
  • Support Year
    01
  • Suffix
  • Award Notice Date
    9/27/2021 - 4 years ago

Fusion of nanomagnetic and viral tools to interrogate brain-body circuits

Abstract The information flow between the peripheral organs and the brain is increasingly recognized as bidirectional, with activity in peripheral circuits influencing high-level behaviors including mood, motivation, and stress. To establish mechanistic links between activity of peripheral neurons and brain circuits, we will develop a species- agnostic framework for targeting and remote modulation of specific cells within the peripheral organs and the brain during behavior. Our framework will combine the homing, modulation, and contrast properties of synthetic magnetic nanomaterials with the targeting specificity of viral vectors. Magnetic nanomaterials have recently emerged as versatile transducers of remotely applied weak magnetic fields into thermal, chemical, or mechanical stimuli perceived by ion channels. We will dramatically expand the palette of magnetic nanotransducers to enable receptor-specific remote magnetic modulation of neurons (or other electrogenic cells) anywhere in the body during free behavior. Moreover, we will leverage recent advances in adeno-associated viral vectors for targeting specific cells and tissues by creating an array of fusions of nanotransducers and viral capsids. This will allow for magnetic guidance and localization of the hybrid magnetic- viral fusions to the locations of interest following systemic delivery regardless of the model organism. We will apply our framework to elucidate circuits connecting the enteric (gut) nervous system to the midbrain structures. Recent work has drawn links between gastrointestinal dysfunction and social and mood disorders as well as demonstrated vagal transmission of the enteric signals to the brain. By applying receptor-specific modulation to the enteric neurons we intend to test the hypothesis that their activity influences midbrain pathways governing reward and motivation, and possibly motor behaviors. In addition to empowering studies of gut-brain circuits, our species-agnostic framework can be extended to investigate connections between any peripheral organ and the brain thus opening opportunities to develop peripheral organ interventions for neurological and mental conditions.

IC Name
National Center for Complementary & Integrative Health
  • Activity
    DP1
  • Administering IC
    AT
  • Application Type
    1
  • Direct Cost Amount
    700000
  • Indirect Cost Amount
    385700
  • Total Cost
    1085700
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    213
  • Ed Inst. Type
    BIOMED ENGR/COL ENGR/ENGR STA
  • Funding ICs
    NCCIH:400000\OD:685700\
  • Funding Mechanism
    Non-SBIR/STTR RPGs
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    MASSACHUSETTS INSTITUTE OF TECHNOLOGY
  • Organization Department
    ENGINEERING (ALL TYPES)
  • Organization DUNS
    001425594
  • Organization City
    CAMBRIDGE
  • Organization State
    MA
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    021421029
  • Organization District
    UNITED STATES