Notch signaling is a highly conserved cell-to-cell communication mechanism, which plays a central role in defining individual cells'behaviors and fates during development. Despite rapidly increasing knowledge of these signaling events, little is known about how spatiotemporal dynamics of receptor signaling across the cell influence signal exchange. To address this challenge, we propose an advanced nanosystem that mimics, enabling simultaneous real-time monitoring and in situ regulation of Notch signaling in a particular cell at any desired location and time with subcellular resolution. Using this new nanotechnology, we first determine force-induced structural features of Notch receptors. We also explore Notch signaling in neural stem cells to determine how the spatiotemporal distribution of Notch signaling across a cell population influences the final fate of individual cels during development. Binary cell communication via Notch.

Public Health Relevance

The proposed new single molecule probes with extreme brightness, high-resolution, photo stability, and magnetic tweezing capability will provide not only specific and sensitive diagnostic tools but also the ability to control stem cell differentiaton with single cell resolution, which has implications for stem cell therapy. Moreover, Notch signaling is an important protein involved in the development of many diseases such as cancer, multiple sclerosis, lymphoma, and other diseases, and thus the understanding of Notch dynamics will be beneficial for diagnostic and therapeutic purposes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM112081-01
Application #
8768214
Study Section
Enabling Bioanalytical and Imaging Technologies Study Section (EBIT)
Program Officer
Flicker, Paula F
Project Start
2014-08-01
Project End
2019-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$287,046
Indirect Cost
$97,046
Name
University of California San Francisco
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143