The Protein Analytics/Characterization team at Invenra is seeking a protein LC-MS analytical Scientist or Senior Scientist to join their expanding team. This position will report to the Director of the Analytics group and provide protein mass spectrometry support for numerous projects relating to Invenra’s protein biotherapeutics development pipeline. The primary duty of this position is to perform intact mass measurements of antibodies, antigens, and other protein constructs using LC-MS techniques. Critical is the ability to troubleshoot and reconcile mass differences between predicted and measured masses and report upon these differences to colleagues and collaborators. Other duties include LC-MS assay development (bottom-up, middle-down/up, top-down), instrumentation troubleshooting (including maintenance/repair), and providing expert-level technical support to Invenra’s numerous pre-clinical protein biotherapeutic programs. Key aspects of the job entail operating an Agilent 6545XT Q-TOF mass spectrometer and 1290 UPLC to support routine protein mass analysis and product quality monitoring. As the protein mass spectrometry team grows, this position will support development of more advanced LC-MS assays to facilitate more rigorous protein characterization (peptide mapping/sequence confirmation, analysis of glycosylation and other post-translational modifications, disulfide bond mapping, drug-antibody-ratio estimation, epitope mapping, etc.).
The position requires mastery of protein mass spectrometry by LC-MS and a knowledge of basic antibody structure and methods of analysis by LC-MS. We seek a candidate with technical mastery of protein sample preparation strategies for LC-MS applications – this is a hands-on, lab-driven position with minimal large-scale bioinformatics needs. The candidate must be familiar with operation and basic maintenance of high-end LC-MS instrumentation and must have a watchful eye to identify early-stage degradation of instrument performance. Experience using LC-MS to analyze biomolecules including mono-/multi-specific antibodies, nanobodies (VHH), cell-surface proteins, and affinity-tagged proteins is highly desired. Familiarity with Agilent’s LC-MS instrumentation and data analysis software is also highly desired. The ideal candidate will skillfully interpret LC-MS results and communicate these findings to non-experts to help make major decisions about project direction.
Ideal candidates will be an innovative thinker with the ability to work independently, design and carry out experiments and propose creative solutions to challenging problems and thus must bring intellectual, professional and personal values that complement the founding team: the highest standard of integrity, a tremendous work ethic and the passion to succeed.
· Characterizing antibodies, antigens, and other engineered proteins by LC-MS. Ensuring data quality meets or exceeds quality criteria.
· Performing as the LC-MS technical lead on project teams.
· Employing new strategies for protein characterization featuring LC-MS techniques.
· Establishing suitable standards and controls for new assays and writing standard operating procedures for use.
· Preparing analytical standards, chromatographic mobile phases, and reagent stocks.
· Performing basic/routine maintenance and instrumentation troubleshooting.
· Analyzing and interpreting data from multiple assays, compiling and reconciling those data with LC-MS outputs, and communicating results to scientific and management stakeholders.
· Mentoring junior scientists and managing research associates.
Knowledge, Skills, and Abilities
- Mastery of protein sample preparation for LC-MS applications. Expertise in chromatographic separations of proteins and operation of sensitive analytical instrumentation is required. Experience with protein chromatography is required.
- Expertise in top-down (intact) protein mass spectrometry is preferred.
- Expertise performing affinity purification/immunoprecipitation is desired.
- Required is the ability sensibly improvise and design new experiments based upon multiple analytical readbacks without significant technical oversight from the Director of Analytics.
- Familiarity with Agilent LC-MS instrumentation and software (MassHunter, Bioconfirm) is highly desired. Experience using Agilent 1100/1200 HPLC systems is a plus.
- Must be capable of expertly interpreting LC-MS data and presenting results to cross-functional teams comprising various scientific disciplines.
- Should be skilled in the area of routine maintenance of LC-MS instrumentation including ionization source/ion optics cleaning, replacing pump seals/pistons, injection valve repair, and replacement of sampling needles and in-line filters. Preference will be shown for candidates with experience with Agilent HPLC and LC-MS instrumentation.
- Must have a solid grasp of the underlying biochemistry/chemistry governing protein modification (endogenous and exogenous) and how that relates to biologically meaningful prevalence in engineered proteins from transient transfection and stable cell line expression.
- Must execute routine work at expected quality with minimal supervisory oversight, but wise enough to know when to ask for help to avoid preventable delays to project timelines.
- Must be willing to mentor junior scientists, manage research associates/interns, and foster a laboratory environment comprising analytical rigor, creativity, and accountability.
- Must adhere to standard operating procedures when required.
- Must be reliable, have a professional attitude, and maintain positive group dynamic through effective and timely communication.
- Should embrace working in a fast-paced environment, with multiple projects and evolving priorities.
Education and Experience
Scientist level: Ph.D.’s without post-Ph.D. work experience. Experience and technical aptitude will be considered as a substitute for formal education for candidates with a bachelor’s or master’s degree with 7+ or 5+ years of LC-MS experience, respectively, relevant to the requirements/preferences for this position.
Senior Scientist level: Senior Scientist level will (1) have a Ph.D. in analytical chemistry, biochemistry, or the biological sciences/physical sciences (molecular and cell biology, physics, etc.) with advanced training with LC-MS, and (2) two or more years of relevant industrial or post-doctoral experience in an LC-MS laboratory.