NIH Common Fund Supports Two Initiatives in 2011 for the Development of Protein Capture Reagents and Technologies
Production of Affinity Reagents for Human Transcription Factors (U54) RFA-RM-10-017
This initiative is aimed at producing an affinity reagent resource for human transcription factors of the broadest possible utility, with a high priority for the use of the reagents in chromatin immunoprecipitation (ChIP) studies. The Protein Capture program is supporting two new awards in this area.
- Dr. Jef Boeke at Johns Hopkins University will create a production center with a highly efficient and cost-effective monoclonal antibody pipeline that will produce protein capture reagents recognizing approximately 1,500-1,700 human transcription factors. Importantly, the group proposes an available distribution plan utilizing the existing Developmental Hybridoma Monoclonal Bank, ensuring broad availability and wide accessibility (1-U54-HG006434-01).
- Dr. Anthony Kossiakoff at the University of Chicago will lead in the establishment of the Recombinant Antibody Network (RAN). RAN is a collaborative international tri-center partnership with the goal of generating customized affinity capture reagents to all human transcription factors. Their proposed pipeline aims to produce recombinant antibodies at least five times faster and at costs far below those of current hybridoma technology. Their goal is to accelerate the rate and reduce the cost of research centered on transcription factors and the proteome (1-U54-HG-006436-01).
Technology Development for New Affinity Reagents Against the Human Proteome (U54) RFA-RM-10-018
This initiative seeks to address a central challenge in the field. While a number of approaches for generating protein affinity reagents exist, the cost and throughput of the current technologies represent significant roadblocks to the development of a comprehensive and broadly available resource of renewable affinity reagents to all human proteins. The development of a robust pipeline that goes from the selection of protein targets to the validation of the produced reagents is greatly needed. This Protein Capture program is supporting four new awards that aim to develop and/or improve approaches for obtaining protein affinity reagents at high throughput and low cost.
- Dr. Andrew Bradbury at Los Alamos National Laboratory, together with an outstanding team of international scientists that include Drs. Aled Edwards, Mathias Uhlen, Lund-Johansen, Daniele Sblattero, and Janet Oliver will establish a pilot, high-throughput, three-tiered antibody selection pipeline that involves yeast and phage display technologies. This approach could potentially increase throughput by ~100 fold compared to the selection and characterization of monoclonal antibodies against each target, resulting in a dramatic reduction in costs. In most cases the result would be a renewable polyclonal antibodies but monoclonal antibodies can also be developed when necessary (1-U54-DK093500-01).
- Dr. John Chaput and Dr. Joshua Labaer at Arizona State University, Tempe will collaborate to further develop bivalent affinity reagents called "DNA synbodies." Synbodies are produced via a novel technology that utilizes a rigid DNA scaffold to produce high affinity protein capture reagents. They will apply this technology to create a relatively inexpensive and high throughput pipeline to produce DNA synbodies to human proteins (1-U54-DK093449-01).
- Dr. Brian Kay at the University of Illinois at Chicago together with Dr Andreas Pluckthun at the University of Zurich, and Dr. Michael Weiner at Illumina will form a research collaboration to improve screening and evaluation technologies currently used to generate affinity reagents. The award will directly compare three types of recombinant protein scaffolds as affinity reagents and two types of display technologies (phage and ribosomal) against the same set of human proteins and will optimize a pipeline for producing recombinant monoclonal antibodies. Furthermore, within this project, the method called Phage Emulsion, Secretion, and Capture (ESCape) will be optimized. This is a novel and ground breaking approach for selection in phage display, where the generation of an emulsion phase allows the compartmentalization of each phage with the antigen linked to beads (1-U54-DK093444-01).
- Dr. Hyongsok Tom Soh and Dr. Yi Xiao at the University of California, Santa Barbara, collaborating with Dr. Lloyd Smith, Dr. James Thomson, and Dr. Ron Stewart at the University of Wisconsin, Madison, will combine three technologies as follows: microfluidic selection, next-generation aptamer sequencing, and surface plasmon resonance (SPR) Imaging to develop a Quantitative Parallel Aptamer Selection System (QPASS) platform that should enable significant process improvements and cost reductions in aptamer generation, reducing the typical 8-10 rounds of aptamer selection to only 3. Aptamer technologies have the main advantage that once an appropriate reagent is generated it can be easily reproduced and distributed at very low cost (1-U54-DK093467-01).
Up to Top