SOLICITATION NOTICE
R -- BIOPHYSICAL SCIENTIST AND EXPERT IN TIME RESOLVED OPTICAL SPECTROSCOPY
- Notice Date
- 8/17/2011
- Notice Type
- Presolicitation
- NAICS
- 611310
— Colleges, Universities, and Professional Schools
- Contracting Office
- National Institutes of HealthNational Library of Medicine6707 DEMOCRACY BOULEVARDII DEMOCRACY PLAZA, SUITE 700WATTN: MS. V. L. GRIFFINBethesdaMD20892-7511
- ZIP Code
- 20892-7511
- Solicitation Number
- NIHLM2011165
- Response Due
- 9/12/2011
- Archive Date
- 10/12/2011
- Point of Contact
- GRIFFIN, VERNE L +1 301 594 7730, griffinv@mail.nih.gov
- E-Mail Address
-
GRIFFIN, VERNE L
(griffinv@mail.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- In accordance with FAR Part 13 Simplified Acquisition Procedures and as documented consistent with FAR 13.501, The National Institutes of Health (NIH) National Institute Diabetes and Digestive and Kidney Diseases (NIDDK) has a requirement to procure the services of the Associate Professor, Department of Physics, University of Parma, biophysical scientist and expert in time resolved optical spectroscopy, laser photodissociation, and fast kinetics. The NIDDK mission includes the planning and execution of research in selected areas of chemistry, physics and biology involving the relationship between molecular structure and function on a wide range of systems of biological interest. There is considerable emphasis on investigations of allosteric regulation in multi-subunit proteins by the binding of small ligands, a widespread phenomenon in biology. Our current understanding of the physical basis of how small ligands alter reactivity is based on the allosteric model of Monod, Wyman, and Changeux (MWC). Allostery has been studied most intensively in hemoglobin. In the case of hemoglobin there are two major postulates of the MWC model. First, binding of oxygen to the 4 subunits in each of the two quaternary structures is noncooperative, cooperativity resulting from the shift in the equilibrium from the low affinity quaternary structure (called "T") to the high affinity quaternary structure (called "R") as successive molecules of oxygen bind. The second key postulate is that regulation of oxygen affinity by protons or other small molecules, such as the physiologically important ligand, 2,3-diphosphoglycerate (DPG, a so-called "allosteric effector"), is achieved by simply altering the equilibrium constant for the quaternary transition, with no affect on the oxygen affinity of either quaternary structure. Objectives The principle objectives of the contacted work are (i) to confirm the interpretation of the previous investigation that the T quaternary structure contains subunits with kinetic properties of the R quaternary structure using a new strategy of continuous photolysis, and (ii) to employ the continuous photolysis approach to determine the kinetic properties of the deoxy subunits in the R quaternary structure. These objectives will take advantage of Viappiani's group ability to fully characterize the kinetic and equilibrium properties of the unstable liganded T and unliganded deoxygenated R conformations by transiently trapping them by encapsulation in the polymeric network of silica gels. The results will provide a critical test of the TTS model, the most promising of the existing theoretical models for allosteric regulation. The TTS allosteric model developed by the Eaton group should serve as a paradigm for a quantitative understanding of allosteric interactions in multi-subunit proteins in general. No other protein has the unique physical properties necessary to investigate allosteric mechanisms in the depth that is possible with hemoglobin. Services to be performed 1. prepare chromatographically pure hemoglobin and encapsulate in silica gels. 2. perform the following class of experiments on both T and R quaternary structures saturated with carbon disoxide and encapsulated in silica gels. A steady state desaturation of the liganded T quaternary structure will be created using a cw laser, followed by measurement of the kinetics of CO rebinding upon shutting off the laser with an acousto-optic modulator. Dr. Viappiani will measure the rebinding kinetics as a function of (a) cw laser power(b) exposure time to cw laser(c) equilibration time with CO prior to cw photodissociation(d) pH(e) CO pressure(f) temperature(g) gel stiffness(h) concentration of allosteric effector 3. Fit ligand binding curves with a sum of exponential and/or stretched exponential functions to determine the amplitudes and relaxation rates as a function of the conditions given in (2). Fit data with TTS model. 4. Measure oxygen binding curves as a function of pH, temperature, and concentration of allosteric effectors. 5. Provide all data and results of fits to NIDDK This notice of intent is not a request for competitive proposals, however, all responses received, before the closing date, of this announcement will be considered by the Government. A determination by the Government not to compete this proposed acquisition is based upon responses to this notice and is solely within the discretion of the Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. It is anticipated that the Request for Quotation (RFQ) NIHLM2011165 will be available fifteen (15) days after the release of this notice. Receipt of quotations will be due ten (10) days after the release of the RFQ. Request for copies of the RFQ must be in writing to the National Library of Medicine, 6707 Democracy Boulevard, Two Democracy Plaza, Suite 700W, Bethesda, MD 20817 Attention: V. Lynn Griffin. FAX quotations must contain offerors name, address, telephone number and fax number. FAX quotations will be accepted if dated and signed by an authorized company representative. FAX NUMBER 301-480-8501. All requests for quotation must include a valid email address. Confidentiality - No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s). PLEASE NOTE: In order to receive an award, contractor must be registered and have valid certification in the Central Contractor Registration (CCR) http://www.ccr.gov.
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