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
Velten, Lars; Haas, Simon F; Raffel, Simon et al. (2017) Human haematopoietic stem cell lineage commitment is a continuous process. Nat Cell Biol 19:271-281
Smith, Justin D; Schlecht, Ulrich; Xu, Weihong et al. (2017) A method for high-throughput production of sequence-verified DNA libraries and strain collections. Mol Syst Biol 13:913
Emaminejad, Sam; Gao, Wei; Wu, Eric et al. (2017) Autonomous sweat extraction and analysis applied to cystic fibrosis and glucose monitoring using a fully integrated wearable platform. Proc Natl Acad Sci U S A 114:4625-4630
Vandova, Gergana A; O'Brien, Robert V; Lowry, Brian et al. (2017) Heterologous expression of diverse propionyl-CoA carboxylases affects polyketide production in Escherichia coli. J Antibiot (Tokyo) 70:859-863
Jensen, Michael; Davis, Ronald (2017) RecJ 5' Exonuclease Digestion of Oligonucleotide Failure Strands: A ""Green"" Method of Trityl-On Purification. Biochemistry 56:2417-2424
Celaj, Albi; Schlecht, Ulrich; Smith, Justin D et al. (2017) Quantitative analysis of protein interaction network dynamics in yeast. Mol Syst Biol 13:934
Lau, Billy T; Ji, Hanlee P (2017) Single molecule counting and assessment of random molecular tagging errors with transposable giga-scale error-correcting barcodes. BMC Genomics 18:745
Greer, Stephanie U; Nadauld, Lincoln D; Lau, Billy T et al. (2017) Linked read sequencing resolves complex genomic rearrangements in gastric cancer metastases. Genome Med 9:57
Esfandyarpour, Rahim; DiDonato, Matthew J; Yang, Yuxin et al. (2017) Multifunctional, inexpensive, and reusable nanoparticle-printed biochip for cell manipulation and diagnosis. Proc Natl Acad Sci U S A 114:E1306-E1315
Shin, GiWon; Grimes, Susan M; Lee, HoJoon et al. (2017) CRISPR-Cas9-targeted fragmentation and selective sequencing enable massively parallel microsatellite analysis. Nat Commun 8:14291

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