Principal Scientist, Structural Biology / Protein Biophysics

Flagship Pioneering, Inc. • Cambridge, MA

10h • $163,000 - $214,500

About The Position

Flagship Labs 132 (FL132), an early-stage biotechnology company addressing unmet needs for patients with amyloidogenic diseases, is seeking a Principal Scientist to help build its amyloid research platform. This hands-on position sits at the interface of protein biophysics, chemical biology, structural biology, and neurodegeneration. The scientist will produce assay-grade amyloid proteins, develop and qualify aggregation and structural assays, and characterize amyloid aggregates to advance therapies for amyloidogenic diseases.

The Principal Scientist will help set scientific and technical direction from the outset, contribute to company strategy in collaboration with Flagship Pioneering leadership, establish experimental methods, and help train a growing team. The role also involves supporting cell-based assays, evaluating inhibitors, managing external research collaborations, and communicating project findings. It offers an early employee the opportunity to help lay the scientific foundation of a platform company, with a role tailored to impactful contributions, professional growth, and scientific interests.

Requirements

• Ph.D. in structural biology, chemical biology, biochemistry, biophysics, physical chemistry, or a related field.
• At least 8 years of relevant industry or postdoctoral experience.
• Hands-on experience with recombinant protein expression, purification, and quality control, ideally involving intrinsically disordered or aggregation-prone proteins.
• Deep expertise in kinetic assays of protein aggregation and familiarity with global kinetic fitting of resulting data.
• Familiarity with amyloid aggregation mechanisms, strain and seeding biology, and cofactor or inducer systems.
• Strong organizational and written and verbal communication skills.
• Ability to contribute as a motivated team player and effective independent contributor.

Nice To Haves

• Experience structurally characterizing proteins and aggregates using mass spectrometry-based approaches such as LiP-MS or HDX-MS.
• Familiarity with cryo-EM, atomic force microscopy (AFM), or NMR.
• Experience with statistical design of experiments (DoE) and analysis of large, time-resolved kinetic datasets.
• Experience managing contract research organizations (CROs).
• Familiarity with cell-based neurodegeneration assays for toxicity, seeding, or clearance.
• Experience with laboratory automation or liquid handling to support screening throughput.
• Adjacent experience in protein biophysics, NMR, cryo-EM of non-amyloid targets, or protein aggregation in biologics development.

Responsibilities

• Contribute to scientific and technical direction with Flagship Pioneering leadership and help shape company strategy.
• Establish in-house production and quality control of assay-grade recombinant amyloid proteins, including seed-free monomer preparation and characterization.
• Design and analyze amyloid aggregation experiments, including kinetic measurements of aggregation.
• Characterize amyloid aggregates using mass spectrometry, NMR, AFM, or related methods.
• Support development of cell-based assays to evaluate amyloid toxicity, seeding, and clearance.
• Evaluate inhibitors of amyloid aggregation and translate findings from biochemical systems into cellular models.
• Scope, contract, and manage CROs and academic collaborations, establishing effective experimental and documentation practices.
• Drive key project goals, ensure rapid and accurate data turnaround, and present experimental results and insights at team meetings.
• Help build experimental methods and train the growing team.

Benefits

• Healthcare coverage.
• Annual incentive program.
• Retirement benefits.
• A broad range of other benefits.
• Monthly social events.
• Community lunchroom with free snacks and coffee.
• Opportunity for professional growth and a role tailored to impactful contributions and scientific interests.

What This Job Offers

• Job Type: Full-time
• Career Level: Principal
• Education Level: Ph.D. or professional degree