GMP, SCIENTIST/ENG-1, BIOPROCESS

This Position is Grant Funded

School of Medicine

Established in 1930, Duke University School of Medicine is the youngest of the nation's top medical schools. Ranked sixth among medical schools in the nation, the School takes pride in being an inclusive community of outstanding learners, investigators, clinicians, and staff where interdisciplinary collaboration is embraced and great ideas accelerate translation of fundamental scientific discoveries to improve human health locally and around the globe. Composed of more than 2,600 faculty physicians and researchers, nearly 2,000 students, and more than 6,200 staff, the Duke University School of Medicine along with the Duke University School of Nursing, and Duke University Health System comprise Duke Health, a world-class academic medical center. The Health System encompasses Duke University Hospital, Duke Regional Hospital, Duke Raleigh Hospital, Duke Health Integrated Practice, Duke Primary Care, Duke Home Care and Hospice, Duke Health and Wellness, and multiple affiliations.

Duke Human Vaccine Institute

The Bioprocess Scientist I will lead the in-house mRNA vaccine process development, including expression vector optimization, GOI codon optimization, in vitro transcription, scale-up of mRNA and LNP production and encapsulation, post purification mRNA quality assessments including purity and intact status as well as removal of double-stranded DNA. The candidate will also be responsible for evaluation of novel lipids working with the DHVI faculty and help advance lipids for evaluation in discovery science. Participates in review of analytical data and troubleshooting technical issues to advance innovative vaccine platform development in support of Phase I clinical trials. Works closely with DHVI faculty, PD leadership, GMP leadership and lab scale process development for mRNA technology development

Responsibilities

Process Development

• Demonstrates knowledge of all aspects of mRNA and LNP process development including working knowledge of GMP manufacturing
• Lead the multi-step experiments to characterize the RNAs and their formulations for in vitro studies
• Comprehensive knowledge and hands on experience in mRNA engineering including UTRs, codon, and structure optimization for enhanced translational assessments
• Hands on experience with cell culture, cell-based assays for characterization of RNA including flow cytometry, BLI, RT-qPCR, and sequencing
• Experience performing and analyzing mRNA translation, RNA secondary structure and RNA folding characterization and mRNA stability analysis
• Experience in designing experiments to characterize the RNAs and their formulations for in vitro and in-vivo studies
• Experience in MS / biophysical method development for characterizing ScDNA, linearized DNA, mRNAs, lipids and lipid nanoparticles (LNPs).
• Experience in academic Mass Spectrometry, Capillary Electrophoresis, Dynamic Light Scattering (DLS), Field Flow Fractionation (FFF), Multi-Angle Light Scattering (MALS).
• Design and Development to enable optimization of mRNA-LNPs and development of formulation science to support stabilization of mRNA-LNPs
• Identification of novel lipids and technologies to help support and advance mRNA process development
• Experience in protein and mRNA purification and experience of purification of complex biomolecules
• Experience with mRNA purification techniques such as chromatography, tangential flow filtration (TFF) and AKTA chromatography systems
• Lead development & optimization of lab scale purification of mRNA and DNA plasmid template
• Collaborate with mRNA downstream process development to develop mRNA separation technologies
• Interact with discovery teams to develop RNA LNP formulations to support in vitro and in vivo assays
• Procure raw materials for development projects to support mRNA development and LNP formulation design
• Experience in bioinformatics, computational biology and biostatistics
• Experience in developing strategies to remove HCP, HCD and other impurities in compliance with phase I manufacturing and regulatory requirements.
• Lead downstream mRNA purification responsibilities include GMP document drafting, in-suite cGMP production, equipment and material management, facility compliance and root-cause investigations.
• Working knowledge of structural modeling of macromolecules and of structural information assessment
• Cross-functional collaboration with cell line development and cell culture PD teams necessary for accelerating development activities to understand process capabilities and impacts on product quality.
• Experience in data analysis and supporting DOE studies to develop scale-up downstream purification schemes.
• Experience in high-throughput resin-screening, supporting early formulation development and screening of potential product quality liabilities.
• Experience with phase-I process development, DOE studies, development of process control strategies including protein conjugation strategies.
• Familiarity with JMP or similar statistical software.
• Single-use technologies, lead and support downstream unit operation development activities.
• Working knowledge of end to end process for manufacturing, experience working in a R&D environment.
• Ability to communicate in a cross functional team setting including in GMP operations, Analytical development, Quality Control and Regulatory affairs teams.

Required Qualifications at this Level

• Education/Training: Bachelor's degree in a science, engineering, or related field. An advanced degree (Master's, PhD) is preferred.
• Experience: 6 years relevant experience in the biopharmaceutical industry or equivalent.
• Skills:
  • Experience in development of cell culture or protein purification techniques and analytical techniques; hands on implementation of bioprocess unit operations (bioreactor control and operation, Chromatography, TFF filtration, GE Unicorn software) and/or direct GMP experience is required.
  • Demonstrates innovation in either upstream (cell culture, bioreactor operation including scale up) or downstream purification (chromatography, tangential flow filtration, normal flow filtration) and analytical techniques to support upstream or downstream activities (cell and metabolite analyses, SDS-PAGE, western blot, UV-Vis, colorimetric methods).
  • Must work independently to develop specific processes or methods in line with strategic program goals.
  • Demonstrated advanced ability in solving complex analytical problems in alignment with strategic project plans.
  • Strong oral and written communication skills.

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Essential Physical Job Functions: Certain jobs at Duke University and Duke University Health System may include essentialjob functions that require specific physical and/or mental abilities. Additional information and provision for requests for reasonable accommodation will be provided by each hiring department.