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Postdoctoral Scientist Bioanalytical Mass Spectrometry

Location

DublinDublin

Company

NATIONAL INSTITUTE FOR BIOPROCESSING RESEARCH AND TRAINING

Date added

08/06/2020

Job Description:

Project Overview: More than 40% of the protein products approved by the US FDA in the past decade are sold as solid powders, usually produced by lyophilization (freeze-drying). Traditionally, developing a lyophilized product has required stability studies to ensure product quality. Because degradation is usually slow, stability studies can take months or even years to complete. This increases time-to-market for new medication and slows manufacturing improvements for existing medications. The Topp lab has developed solid-state hydrogen deuterium exchange with mass spectrometric analysis (ssHDX-MS) as an alternative to stability studies for proteins in solid powders. ssHDX-MS takes just days to complete and the results have been shown to be highly correlated with various forms of protein instability on storage, including aggregation and deamidation. As a result, the method is increasingly being evaluated and adopted by the biopharmaceutical industry as a formulation and process development tool. This project will develop the fundamental theory of ssHDX-MS and apply that understanding to establish standardardized analytical approaches and data analysis strategies for ssHDX-MS. The approaches will be applied to samples generated in-house and/or received from the biopharmaceutical industry. Objectives of the project include: • To develop experimental and data analysis methods that enable robust interpretation of ssHDX-MS data • To document standardized ssHDX-MS procedures to facilitate transfer to the industry • To support adoption of ssHDX-MS as a bioanalytical service offered by NIBRT Applications are sought from a motivated postdoctoral scientist to develop and standardise ssHDX-MS methods for the analysis of protein conformation and matrix interactions in lyophilized solids. The successful candidate will develop experimental and data analysis methods that enable robust interpretation of ssHDX-MS data. Activities may include proposing and assessing protein/peptide standards for ssHDX-MS, preparation and analysis of controls (e.g., for folding, back exchange) and the development of models to support analysis of ssHDX-MS kinetic data. The successful candidate will document these procedures to facilitate dissemination to analytical services laboratories and the biopharmaceutical industry.Additionally, the candidate will actively participate in analysing ssHDX-MS samples submitted to NIBRT. The appointed postdoc will work closely with graduate students, visiting scientists and the project PI, and will be responsible for planning lab activities, executing the experiments and reporting on project outcomes to the PI and collaborators. Essential qualifications and experience: • PhD in Analytical Chemistry, Bioanalytical Chemistry, Pharmaceutical Chemistry/Pharmaceutics, Chemical/Biochemical Engineering or closely-related discipline • Proven practical experience in the use of LC-MS methodologies for protein identification and quantitation • Proven 

Term

Permanent / Full-time

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