- Innovation In the first tier of the proposal. Technology Innovation, we are pioneering several technologies for molecular and cell-specific profiling. We are building targeted molecular probes that alter the function of individual proteins or protein complexes, which will be used to map tissue-specific cellular phenotypes. Complex natural product molecules are useful for probing individual proteins and pathways, but they are difficult to chemically synthesize or extract from nature. We are using synthetic DNA to engineer E. coli and yeast hosts for combinatorial biosynthesis of complex natural products. We will use these probes to interrogate human protein complexes using a novel high-throughput protein-protein interaction assay. Probes displaying distinct molecular phenotypes in the protein assay will be analyzed further using a digital microfluidic human cell viability assay. Once the probes are developed and the protein targets are determined, we will assess clinically relevant cell populations. To accomplish this, we will build a platform for the isolation of cancer cells from blood and develop novel methodologies for real-time detection of biomolecules in single cells. These pioneering efforts will shed light on the practical application of these technologies to (1) engineer and utilize natural product probes intractable to chemical synthesis, and (2) enrich rare, living cells for clinical analysis.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Program Projects (P01)
Project #
5P01HG000205-25
Application #
8738702
Study Section
Special Emphasis Panel (ZHG1-HGR-N)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
25
Fiscal Year
2014
Total Cost
$1,859,417
Indirect Cost
$634,270
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Li, Yong Fuga; Tsai, Kathleen J S; Harvey, Colin J B et al. (2016) Comprehensive curation and analysis of fungal biosynthetic gene clusters of published natural products. Fungal Genet Biol 89:18-28
Lefterova, Martina I; Shen, Peidong; Odegaard, Justin I et al. (2016) Next-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis. J Mol Diagn 18:267-82
Nascimento, Raphael A S; Özel, Rıfat Emrah; Mak, Wai Han et al. (2016) Single Cell "Glucose Nanosensor" Verifies Elevated Glucose Levels in Individual Cancer Cells. Nano Lett 16:1194-200
Pelechano, Vicent; Wei, Wu; Steinmetz, Lars M (2016) Genome-wide quantification of 5'-phosphorylated mRNA degradation intermediates for analysis of ribosome dynamics. Nat Protoc 11:359-76
Gao, Wei; Emaminejad, Sam; Nyein, Hnin Yin Yin et al. (2016) Fully integrated wearable sensor arrays for multiplexed in situ perspiration analysis. Nature 529:509-14
Padovani, José I; Jeffrey, Stefanie S; Howe, Roger T (2016) Electropermanent magnet actuation for droplet ferromicrofluidics. Technology (Singap World Sci) 4:110-119
Emaminejad, Sam; Paik, Kee-Hyun; Tabard-Cossa, Vincent et al. (2016) Portable Cytometry Using Microscale Electronic Sensing. Sens Actuators B Chem 224:275-281
Mankos, Marian; Persson, Henrik H J; N'Diaye, Alpha T et al. (2016) Nucleotide-Specific Contrast for DNA Sequencing by Electron Spectroscopy. PLoS One 11:e0154707
Özel, Rıfat Emrah; Kahnemouyi, Sina; Fan, Hsinwen et al. (2016) Smartphone Operated Signal Transduction by Ion Nanogating (STING) Amplifier for Nanopore Sensors: Design and Analytical Application. ACS Sens 1:265-271
Steinmetz, Lars M; Jones, Allan (2016) Sensing a revolution. Mol Syst Biol 12:867

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