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Opportunity at National Institute of Standards and Technology (NIST)

Development of Nuclear Magnetic Resonance for Applications to Biopharmaceutical Product and Process Characterization

Location

Material Measurement Laboratory, Biomolecular Measurement Division

RO# Location
50.64.51.C0591 Gaithersburg, MD

Please note: This Agency only participates in the February and August reviews.

Advisers

Name E-mail Phone
Arbogast, Luke W larboga1@umd.edu 240.314.6270

Description

In the past decade, Nuclear Magnetic Resonance (NMR) has grown from an emerging method with promise to improve the structural characterization of biotherapeutics to mature method seeing increased adoption by the industry. In that time a number of different NMR approaches have been proposed and developed for such characterization, including 1D 1H-based methods as well as 2D, 1H-13C methyl correlated methods. Both approaches have relative performance attributes related to their inherent resolution and sensitivity. 1D 1H-based methods offer high sensitivity and cover the complete chemical environments of the protein, but accordingly suffer from poor resolution, whereas 2D methyl based methods offer high spectral and structural resolution, but report on only a subset of protein environments and are of low sensitivity at natural isotopic abundance. Given the complimentary nature of the two approaches it is incumbent to develop an integrated and fit-for-purpose multi-modal (1D/2D) approach for NMR characterization of biotherapeutics.

This project will continue the development and validation of product and process analytical measurements using NMR as a multi-modal platform in combination with chemometric tools such as multivariate processing by Principal Component Analysis (PCA). The post-doc will have his/her primary duty station at NIST but will have the opportunity to work in collaboration with biopharmaceutical scientists at leading industry companies.
Candidates with recent PhD degrees in chemistry, biochemistry, or a related field are encouraged to apply. A strong background in NMR spectroscopy is preferred, and experience with protein biochemistry and biophysics would be advantageous.

Referecnces:

Arbogast, L.; Brinson, R.; Marino, J. "Mapping Monoclonal Antibody Structure by 2D
13C NMR at Natural Abundance" Analytical Chemistry, 2015 (87) 3556-61.

Arbogast, L.;Delaglio, F.; Schiel, J.;Marino, J. "Multivariate Analysis of Two-Dimensional 1H,13C Methyl NMR Spectra of Monoclonal Antibody Therapeutics to Facilitate Assessment of Higher Order Structure" Analytical Chemisty, 2017 (89), 11839-45.
Arbogast, L.;Delaglio, F.;Tolman,J.;Marino, J. "Selective Suppression of Excipient Signals in 2D 1H-13C Methyl NMR Spectra of Biotherapeutic Products" Journal of Biomolecular NMR, 2018 (72) 148-161.

Keywords:
nuclear magnetic resonance (NMR); chemometrics; biotherapeutics

Eligibility

Citizenship:  Open to U.S. citizens
Level:  Open to Postdoctoral applicants

Stipend

Base Stipend Travel Allotment Supplementation
$72,750.00 $3,000.00
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