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Form of workPosition Overview
We are currently seeking a motivated, creative, and experienced scientist with expertise in protein production and structure biology to join our growing team focused on Protein Sciences. The successful candidate will have significant experience with protein production and purifications from E. coli, mammalian, and other common protein expression systems and expertise in protein structure biology and mechanistic cell-free and cellular assays. Experience with RNAguided gene editing systems, nucleases, reverse transcriptases, or other polymerases is highly desirable. The ideal candidate will be proactive, enthusiastic, collaborative, and demonstrate communication, with a desire to "lead from the lab" to innovate novel protein production methods and explore mechanism-driven hypotheses to improve Prime Editing technologies.
Key Responsibilities:
- Develop, optimize, and execute protein production workflows (production and purification) that enable the production and characterization of new novel prime editors and other proteins required by Prime Medicine
- Lead structural biology efforts, including high-resolution methods such as crystallography and Cryo-EM studies in complement with lower resolution methods such as DSF, UV-Vis, and CD to characterize in-house prime editor complexes
- Drive a deeper understanding of prime editor RNA protein complexes from a biochemical and biophysical perspective, including the innovation of new techniques to improve Prime Editing in various delivery contexts (RNP, mRNA/LNP, AAV)
- Lead cell-based assay development and execution to characterize RNP delivery and editing potency in therapeutic contexts (Primary cells, iPSCs, T-cells, etc..).
- Perform data analysis and interpretation and present findings in both small team and company-wide settings
- Collaborate cross-functionally across the organization, including supporting RNP delivery efforts, automation, screening, pharmacology, and program teams to enable RNP-based prime editing systems and support program advancement in pre-clinical settings.
- Oversee day to day technical execution of projects from junior team members in the laboratory.
- Maintain thorough electronic lab notebooks and documentation records
- Adhere to all laboratory safety requirements and procedures, assist in maintaining general laboratory functionality, including lab equipment maintenance and the ordering, and receiving of lab supplies
- Create and write reports and SOPs to support development and regulatory filings
Qualifications:
- PhD in Protein Structure Biology, Cellular or molecular biology, Synthetic biology, chemical biology, Biochemistry, or related disciplines with 3+ years of industry experience preferred, or equivalent (BS 8+, MS 6+) at the senior scientist level or (BS 15+, MS 10+) years at the principal scientist level
- Extensive experience with optimization of protein expression across multiple expression systems, including E. coli, insect, and mammalian systems. Process scaling is advantageous.
- Expertise in purification of proteins on AKTA FPLC with experience using various chromatographic methods.
- Proficiency in mammalian tissue culture techniques, including familiarity with primary cells and therapeutically relevant model cell line culture and cell line generation. Experience with a variety of cell-based and molecular biology readout technologies, such as flow cytometry, RT-qPCR / ddPCR, ELISA, RIP-Seq, and cellular imaging techniques, are a plus.
- Strong working knowledge of biochemical and biophysical characterization methods and their applications. Must have hands-on experience with MST, BLI, DSF, UV-Vis, and fluorescence spectroscopy. Mass spectrometry experience is advantageous.
- Familiarity with Next Generation Sequencing
- Experience with molecular biology techniques, but not limited to expression vector design and cloning techniques (GoldenGate, Gibson, etc)
- Broad knowledge and background in nucleases and/or nucleic acid interacting proteins
- Experience leading and collaborating cross-functionally with chemistry, Biology, pharmacology, and program team partners
- Capable of continuous learning, open-minded, curious, highly organized, and detail-oriented with excellent written and verbal communication skills
