Distinct from the common impression, the genomes of individual cells in our body are not exactly homogenous or static. Heterogeneity and dynamic changes occur in many cases, such as aging, cancer and HIV infection. Detecting these single cell events in a live animal remains a major challenge. In the proposed project, we plan to validate and further develop our recently invented CRISPR imaging technique in a multicellular organism. This technique utilizes the CRISPR/Cas9 system to fluorescently label specific, endogenous genomic loci for microscopy detection. Here, we will use the nematode C. elegans as the model organism to validate and benchmark CRISPR imaging as a technology to measure the size of repetitive genomic elements such as telomeres as well as the copy number of genes. We will also improve the sensitivity of CRISPR imaging for the detection of non-repetitive genomic elements. Finally, we will apply CRISPR imaging to the study of telomere length change at the single cell level during C. elegans development and aging.

Public Health Relevance

We propose to validate and further develop our recently invented CRISPR imaging technology as a tool to analyze the size, copy number, and other aspects of genomics elements such as telomeres in a live animal. This tool will be instrumental in monitoring genomic events as in aging, cancer and HIV infection, etc.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
1R33EB019784-01
Application #
8832139
Study Section
Special Emphasis Panel (ZRG1-BST-A (50))
Program Officer
Conroy, Richard
Project Start
2014-09-25
Project End
2017-06-30
Budget Start
2014-09-25
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
$343,644
Indirect Cost
$93,644
Name
University of California San Francisco
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143