Notch is a transmembrane receptor involved in cell fate decisions in diverse organisms ranging from Drosophila to humans. Recently, signaling through Notch has been implicated in multiple cell fate decisions in lymphocyte development. Despite the evidence supporting a role for Notch, how Notch activity is regulated during lymphocyte development is not known. One of the proteins implicated in the regulation of Notch is Numb. Numb is an adapter protein that binds to Notch and inhibits its activity. The major aim of this proposal is to examine the role of Numb in lymphocyte development. To achieve this we will use several complementary approaches.
Specific aim 1 will test the effect of overexpression of Numb and a dominant negative form of Numb in T cell lineage determination.
Specific Aim 2 will test the effect of Numb deficiency in T cell lineage determination in vivo using a thymocyte specific conditional Numb knockout. Lastly, specific Aim 3 will test the role of Numb in B versus T cell lineage determination.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI050415-02
Application #
6511641
Study Section
Special Emphasis Panel (ZRG1-IMB (20))
Program Officer
Prograis, Lawrence J
Project Start
2002-07-01
Project End
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$44,212
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Anderson, Ana C; Kitchens, Elizabeth A; Chan, Shiao Wei et al. (2005) The Notch regulator Numb links the Notch and TCR signaling pathways. J Immunol 174:890-7