Principal Scientist, Pooled Functional Screening

Socket.dev

Cambridge (MA)

On-site

USD 163,000 - 215,000

Full time

8 days ago

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Benefits offered by this job

Early-employee equity

Weekly lunches

Monthly social events

Free snacks and coffee

Job summary

FL130 (Flagship Labs 130) is seeking a Principal Scientist to design, stand up and run high-throughput pooled screening campaigns. The role involves creating large libraries, running pooled FACS-based screens, and guiding data analysis from library production to sequencing readouts.

The successful candidate will lead the science from day one and help build the team, with ownership of technical direction and cross-functional collaboration across Flagship Pioneering portfolio companies.

Qualifications

PhD required with 10+ years industry/postdoc experience; senior-level candidate.
Extensive hands-on experience with high-throughput pooled screens using FACS-based selection.
Proficiency designing DNA/oligo libraries for high-throughput screening with barcoding considerations.
Strong flow cytometry and cell sorting expertise; panel design and maintenance of sorters.
Hands-on experience culturing and screening in primary/primary-like cell lines, including difficult-to-transduce lines.
Experience with lentiviral transduction, production, titering, and ensuring coverage/representation.
Experience with genomic sequencing prep and analysis to identify barcodes/variants.
Motivated team-player with leadership, organizational, and strong communication skills.

Responsibilities

Plan, execute, and analyze high-throughput pooled screens using FACS as primary selection modality.
Design and build DNA/oligo libraries for high-throughput screening with barcoding strategies.
Develop and optimize FACS-based selection strategies across various cell lines.
Culture and screen in primary/primary-like cell models; maintain viability and representation.
Produce and transduce lentiviral libraries; optimize MOI and coverage.
Prepare sorted populations for sequencing; generate barcode-readout workflows.
Analyze sequencing data to call hits and assess reproducibility.
Improve workflows; establish best practices for rapid, quality data turnaround.
Collaborate with protein-engineering and translational teams to connect library design to validation.
Translate data into insights and present at team meetings.

Skills

HTP pooled screens with FACS

DNA/oligo library design

Flow cytometry & cell sorting

Culturing primary/primary-like cells

Lentiviral transduction & titering

Data analysis of sequencing results

Scientific leadership & communication

Education

PhD in molecular/cell biology, genetics, bioengineering

Tools

Flow cytometer

Lentiviral production setup

Genomic sequencing prep

Job description

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 byFlagship 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.

Position Summary

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.

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.

Must-have Qualifications

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.

Preferred Experience

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).

What We Can Offer You

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 Pioneering’s 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.

Privacy Notice for Applicants: When you apply for a role at Flagship Pioneering or one of its portfolio companies, we collect and use personal information you provide (such as your name, contact details, work history, and application materials) to evaluate your application, communicate with you, and comply with legal obligations. Your application data is processed through Greenhouse, our applicant tracking system, and may also be reviewed using AI-assisted screening tools. We do not sell your personal information. California residents have rights under the CCPA/CPRA including to know, delete, and opt out of the sharing of your personal information. If you are located in the EU or UK, we process your data under GDPR and you have rights to access, rectify, and erase your data. To exercise your rights or for questions, contact privacy@flagshippioneering.com.

The salary range for this role is $163,000 - $214,500. Compensation for the role will depend on a number of factors, including a candidate’s 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 FL130's good faith estimate as of the date of publication and may be modified in the future.