RESEARCH PROPOSAL: Notch is a transmembrane protein with multiple EGF- like repeats in the extracellular domain and ankryn repeats in the cytoplasmic domain. During embryogenesis, Notch function is required to suppress neuronal differentiation and in the absence of Notch neurons are overproduced at the expense of epidermal cells. Vertebrate Notch homologs are known and are also implicated in neural development and are associated with certain cancer syndromes. Notch may also function in regulating c ell adhesion as Notch interacts directly with the disheveled protein and thereby antagonizes wingless and cadherin signaling. Dr. Piepenhagen proposes to study the role of Notch subcellular localization in its function. First he plans to determine whether Notch is associated with septate or adherens junctions in Drosophila wing discs. Then he proposes to examine which domain of the Notch protein is essential for this function by looking at the localization of deleted forms of Notch and by looking to see if any domain of Notch can confer Notch-like localization to a heterologous membrane protein. The rationale is solid, the experiments are technically straightforward and the studies should provide some fundamentally new insight into Notch structure and function.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM019129-03
Application #
2910028
Study Section
Special Emphasis Panel (ZRG2-CBY-1 (01))
Program Officer
Flicker, Paula F
Project Start
1998-04-24
Project End
Budget Start
2000-04-24
Budget End
2001-04-23
Support Year
3
Fiscal Year
2000
Total Cost
$37,516
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199