Principal Scientist, Pooled Functional Screening

Company Summary

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.

FL130 is backed by Flagship Pioneering a company that invents and builds platform companies each with the potential for multiple products that transform human health sustainability and beyond. Since 2000 Flagship has originated and fostered the development of more than 100 scientific ventures advancing human health and sustainability including Moderna Generate Biomedicines and Alltrna.

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 companys 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.

Key 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.

• 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.

• 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).

• The opportunity to lay the scientific foundation of a transformative platform company as an early employee.
• A custom-tailored role designed to maximize impactful contributions professional growth and your scientific interests.
• Weekly lunches monthly social events and a community lunchroom with free snacks and coffee all embedded in a vibrant community of scientists and entrepreneurs across multiple Flagship Pioneering portfolio companies.

We are seeking individuals with an entrepreneurial spirit strong communication skills and comfort in working in and contributing to a dynamic cross-functional team environment. The level of the role will be commensurate with the education and years of experience of the identified candidate.

Flagship Pioneering and our ecosystem companies are committed to equal employment opportunity regardless of race color ancestry religion sex national origin sexual orientation age citizenship marital status disability gender identity or Veteran status.

Recruitment & Staffing Agencies: Flagship Pioneering and its affiliated Flagship Lab companies (collectively FSP) do not accept unsolicited resumes from any source other than candidates. The submission of unsolicited resumes by recruitment or staffing agencies to FSP or its employees is strictly prohibited unless contacted directly by Flagship Pioneerings internal Talent Acquisition team. Any resume submitted by an agency in the absence of a signed agreement will automatically become the property of FSP and FSP will not owe any referral or other fees with respect thereto.

The salary range for this role is $163000 - $214500. Compensation for the role will depend on a number of factors including a candidates qualifications skills competencies and experience. FL130 currently offers healthcare coverage annual incentive program retirement benefits and a broad range of other benefits. Compensation and benefits information is based on FL130s good faith estimate as of the date of publication and may be modified in the future.

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