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Tools for High-Throughput Protein Crystallization and Structure Determination

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2011 / STTR
Agency Tracking Number:
R42GM075361
Solicitation Year:
2011
Solicitation Topic Code:
NIGMS
Solicitation Number:
PA10-051
Small Business Information
MITEGEN, LLC
95 BROWN RD, STE 183 ITHACA, NY -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 2011
Title: Tools for High-Throughput Protein Crystallization and Structure Determination
Agency: HHS
Contract: 2R42GM075361-02A1
Award Amount: $249,999.00
 

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.

Principal Investigator:

Robert E. Thorne
607-592-8812
robert.thorne@mitegen.com

Business Contact:

Robert Thorne
607-592-8812
robert.thorne@mitegen.com
Small Business Information at Submission:

MITEGEN, LLC
95 BROWN RD, STE 183 ITHACA, NY -

EIN/Tax ID: 104379145
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
CORNELL UNIVERSITY
373 Pine Tree Road
Office of Sponsored Programs
ITHACA, NY 14850-2820
Contact: