Tools for High-Throughput Protein Crystallization and Structure Determination

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$249,999.00
Award Year:
2011
Program:
STTR
Phase:
Phase II
Contract:
2R42GM075361-02A1
Award Id:
n/a
Agency Tracking Number:
R42GM075361
Solicitation Year:
2011
Solicitation Topic Code:
NIGMS
Solicitation Number:
PA10-051
Small Business Information
95 BROWN RD, STE 183, ITHACA, NY, -
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
170774231
Principal Investigator:
ROBERT THORNE
(607) 592-8812
robert.thorne@mitegen.com
Business Contact:
ROBERT THORNE
(607) 592-8812
robert.thorne@mitegen.com
Research Institution:
CORNELL UNIVERSITY

373 Pine Tree Road
Office of Sponsored Programs
ITHACA, NY, 14850-2820
() -
Nonprofit college or university
Abstract
DESCRIPTION (provided by applicant): Our understanding of the molecular mechanisms of life is increasingly based upon our knowledge of the three dimensional structure of proteins, nucleic acids, viruses and biomolecular complexes. Structure provides insight into function (or malfunction), and provides a starting point for modern drug discovery and molecular medicine. Biomolecular structures are most often determined using X-ray crystallography of crystallized biomolecules. Over the last decade, high-throughput methods have been introduced that have automated many aspects of protein expression, purification, crystallization and crystallography, and that have lowered the cost per structure determined. However, the growth and harvesting of protein crystals remains a major bottleneck in the pipeline from gene to three-dimensional molecular structure and from structure to pharmaceutical therapy. This Phase II STTR proposal is focused on developing and commercializing improved methods for conventional and high-throughput crystallization and for crystal harvesting and X-ray data collection. An examination at Cornell University of how liquid contact lines interact with surfaces has led to a simple technology for precisely defining the positions of dispensed liquid drops and firmly holding them to those positions, regardless of their chemical composition. This technology forms the basis for a new approach to protein crystallization plates that eliminates the liquid-confining wells of conventional plates. These new plates promise to provide precise control over drop position and shape, resulting in more reproducible crystallization kinetics and simplified image analysis. They will allow hanging and sitting drop growth of soluble and membrane proteins using a single plate, and in situ optical, UV and X-ray analysis with low background. They will meet a critical need for plates optimized for easy X-ray examination of screening and crystallization outcomes and also allow in situ structure determination. They will be compatible with all existing drop dispensing and plate handling hardware, lowering barriers to market entry. This project will continue the scientific and commercial development of these plates and explore other biomedical applications of drop pinning technology.In Phase I we successfully developed and commercialized several new tools for crystal retrieval and X-ray data collection. We will continue this development in Phase II, focusing on improved tools for microcrystallography, for automated sample mounting, and for X-ray beam alignment and energy measurement. Together, these technologies should have significant impact on the productivity of high- throughput structural genomics and drug discovery efforts. PUBLIC HEALTH RELEVANCE: Our understanding of themolecular mechanisms of life is increasingly based upon our knowledge of the three dimensional structure of proteins, nucleic acids and viruses. Structure provides insight into function (or malfunction), and provides a starting point for modern drug discovery and molecular medicine. This project will develop and commercialize new technologies for use in determining the protein structures by X-ray crystallography that promise to speed up the progression from gene to pharmaceutical therapy.

* information listed above is at the time of submission.

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