Single cell genomics has transformed biology by enabling unbiased molecular identification and characterization of the full panoply of cell types that make up a tissue. A 'marriage' between this molecular information, which includes an inventory of all the ligands and receptors expressed by each cell class, and the accompanying 3D spatial information about them will enable the comprehensive reconstruction of the active signaling centers within a given tissue. Here, by continuing a fruitful collaboration between a biologist and molecular biochemist, we propose to deliver a transformative new technology for 3D multi-dimensional molecular imaging in intact human tissue. A major strength of our approach is that we entirely bypass the intrinsic limitations of fluorescent imaging, namely endogenous autofluorescence, low signal to noise, and restriction to five or fewer data channels, by using lanthanide resonant energy transfer. By so doing, we will simultaneously overcome challenges in detection of individual signals and massively increase throughput. Furthermore, the technology we deliver will be both biologist 'friendly' and low cost, providing a widely available and practical platform that will be rapidly and broadly adopted by scientists worldwide.

Public Health Relevance

Our research focuses on making it possible to efficiently analyze individual cells in intact human tissues. This capability will be instrumental for understanding the 'logic' of how tissues function and will provide a healthy 'blueprint' against which to compare organs in states of disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Project #
5UG3HL145623-02
Application #
9782994
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Srinivas, Pothur R
Project Start
2018-09-15
Project End
2020-06-30
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Stanford University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305