Principal Scientist, Pooled Functional Screening

Flagship Pioneering, Inc.•Cambridge, MA

4h•$163,000 - $214,500•Onsite

About The Position

FL130 (Flagship Labs 130) is an early-stage biotechnology startup aiming to answer an ambitious and exciting question: What if… we could systematically identify bioactive peptides to inspire next-generation therapies and uncover novel targets? To answer this question, FL130 is pioneering a novel approach to peptide screening, and is recruiting a team of top-tier scientists to help build it. This is a unique opportunity to be one of the first employees of a biotech startup that combines an innovative mindset with the resources and know-how of Flagship Pioneering. We are seeking a motivated and highly collaborative Principal Scientist to design, stand up and run high-throughput pooled screening campaigns. The successful candidate will have a strong track record designing large libraries for high-throughput screening as well as running pooled, FACS-based screens, from library production and transduction through selection, sequencing, and analysis (including culturing and screening in primary and primary-like cell lines). This role is among the first hires, affording the exciting opportunity to shape and influence the company’s scientific direction. This is a hands-on role with substantial ownership for a scientist who is excited to set technical direction from day one and, over time, help build the team.

Requirements

PhD. in molecular or cell biology, genetics, bioengineering, or a similar field with 10+ years of industry or postdoctoral experience (level commensurate with experience).
Extensive hands-on experience running high-throughput pooled screens with FACS-based selection, owning planning, execution, and analysis end to end.
Proficiency designing DNA and oligo libraries for high-throughput screening, with a strong grasp of library design considerations (diversity, coverage, barcoding, and synthesis constraints).
Strong flow cytometry and cell-sorting expertise, including panel design considerations, operation troubleshooting and maintenance of cell sorters.
Hands-on experience culturing and screening in primary and primary-like cell lines, including difficult-to-transduce lines.
Familiarity and comfort with lentiviral transduction, production, and titering, and with managing coverage and representation.
Experience with genomic sequencing preparation and with analyzing sequencing data to identify barcodes or variants.
A motivated team-player with strong organizational skills, leadership instincts, and written and verbal communication skills who takes initiative and drives creative scientific direction proactively.

Nice To Haves

Bioinformatics fluency for count-based screen analysis and scripting in Python and/or R.
NGS QC (TapeStation / Bioanalyzer, qPCR) and Illumina workflows.
Awareness of pooled-screening pitfalls (template switching, barcode collision, multiple integration) and mitigations.
Understanding of the secretory pathway, folding, and post-translational modifications.
Comfort setup and use of electronic lab notebooks (e.g., Benchling).

Responsibilities

Plan, execute, and analyze high-throughput pooled screens using FACS as the primary selection modality, owning the full experimental cycle end to end.
Design and build custom DNA and oligo libraries for high-throughput pooled screening, including barcoding strategies that link genotype to construct.
Develop and optimize FACS-based selection strategies (gating logic, sort schemes, multi-parameter panels) across a range of cell lines, including primary-like and difficult-to-transduce lines.
Culture and screen in primary and primary-like cell models, adapting workflows to maintain viability and library representation.
Produce, transduce, and functionally titer lentiviral libraries; optimize MOI, coverage, and representation.
Prepare sorted populations for next-generation sequencing; build and run genomic / amplicon sequencing preparation and barcode-readout workflows to deconvolve which library members are enriched or depleted.
Analyze sequencing data to call hits (enrichment statistics, controls, and reproducibility).
Optimize existing workflows and establish best experimental and documentation practices to enable platform excellence and rapid, accurate data turnaround.
Partner with protein-engineering and translational colleagues to close the loop between library design, screen design, and downstream validation.
Translate data into insights and present at team meetings.