This proposal is a renewal application for the Stanford Genome Technology Center Grant. Over the last two decades, we have demonstrated a strong track record of technology development by taking an innovative and highly synergistic approach. The proposed research continues in the same direction by leveraging the multidisciplinary environment of the center, but seeks to address the more urgent problems related to the practice of clinical medicine. Our efforts are aimed at advancing the long-term goals of NHGRI with an emphasis on cost reduction, and are designed to have a maximum impact on biomedical research. We propose three tiers of technology development that offer an improved ability to query the human genome and investigate the mechanisms underlying disease. The first tier is Technology Innovation, representing technologies that are in their infancy. Although high risk, these technologies are designed to be pioneering with the potential for high reward. We will create an E. coli and yeast system for the production of engineered natural products to be used as molecular probes, and we will develop an improved method for the isolation and molecular analysis of single live cells (e.g. cancer cells) from blood. The second tier is Technology Development, which is a refinement of technologies that were in the innovation phase in the previous funding period. Having met initial milestones, these technologies will now be tempered to demonstrate improvements over existing technologies. This tier includes a method for the label-free Nano mechanical detection of nucleic acids, and two methods for the high-throughput digital detection of proteins from minute samples. The third tier is Technology Implementation. Technologies in this tier have demonstrated sound proof of concept and are primed for direct application to specific clinical problems. We will apply targeted resequencing methods to identify rare genetic variants in cancer and provide accurate HLA typing for organ transplantation, and our transcriptome microarray will be tailored for the cost-effective analysis of clinical samples to investigate changes in gene expression. With this trove of emerging new tools and wealth of collective experience at SGTC, we expect to improve the course of biomedical research, expand the scope of biological and clinical questions that can be addressed, and accelerate the transfer of technology from the bench to the bedside.

Public Health Relevance

Our goal is to better equip the scientific and medical community with genomic tools that address the urgent problems facing clinical medicine today. We emphasize cost reduction as a means of making new technologies available to the medical community, with the Downstream effect of enabling better patient care.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Program Projects (P01)
Project #
5P01HG000205-25
Application #
8738701
Study Section
Special Emphasis Panel (ZHG1-HGR-N (J1))
Program Officer
Smith, Michael
Project Start
1997-08-01
Project End
2017-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
25
Fiscal Year
2014
Total Cost
$4,900,000
Indirect Cost
$1,715,312
Name
Stanford University
Department
Biochemistry
Type
Schools of Medicine
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

Showing the most recent 10 out of 202 publications