Senior Scientist, Small Molecule Screening

Flagship Pioneering•Cambridge, MA

About The Position

Flagship Labs 129 (FL129) is an early-stage biotechnology startup with an ambitious and exciting mission: to unlock the future of small molecule drug discovery. FL129 is developing a revolutionary approach to this challenge and is recruiting a team of top-tier scientists to build this powerful and first-in-category platform. 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. 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. We are seeking a motivated and highly collaborative Senior Scientist to join FL129’s growing team of experimental and computational scientists to build a novel platform technology. The successful candidate will have a strong track record of scientific and technical innovation in DNA-encoded library (DEL) design, synthesis, and affinity-based selection. Deep experience with DNA-compatible chemistry and with hit deconvolution and validation is essential, and additional experience with cheminformatic analysis of chemical space and library diversity is strongly desired. The ideal teammate will be highly adaptable, have strong organizational and communication skills, and will thrive in a highly collaborative and multidisciplinary environment.

Requirements

Ph.D. in organic chemistry, medicinal chemistry, chemical biology, or a similar field with 5+ years of industry or postdoctoral experience.
End-to-end experience with DNA-encoded library (DEL) screening, from library design and synthesis through affinity selection, next-generation sequencing, and hit deconvolution.
Hands-on expertise in DNA-compatible chemistry, including split-and-pool combinatorial synthesis, building-block validation, and development or adaptation of reactions to on-DNA conditions.
Experience with encoding and tagging strategies, including barcode design and enzymatic ligation, and with analytical quality control of library synthesis (e.g., LC-MS).
Experience with affinity selection formats and their controls, including immobilized and solution-phase targets, matrix and negative selections, and DNA-encoded positive controls.
Experience with on-DNA and off-DNA hit validation, including resynthesis and biochemical/biophysical assays to confirm and quantitate the bioactivity of screening hits.
Experience managing contract research organizations (CROs).
Motivated team-player and independent force-of-nature with strong organizational and written/verbal communication skills.

Nice To Haves

cheminformatics experience, including library enumeration and chemical space or diversity analysis
droplet-based screening and/or microfluidics
laboratory automation and liquid handling.

Responsibilities

Technology development, aligned with FL129’s core strategic goals.
Design, construction, and quality control of DNA-encoded small molecule libraries, including building-block selection and validation
Execute and optimize affinity-based selections against protein targets, including appropriate control selections and enrichment analysis
Deconvolute and validate screening hits, including off-DNA resynthesis and confirmation of activity
Optimize existing workflows and establish best experimental and documentation practices to enable platform excellence.
Ensuring rapid and accurate turnaround of data to drive achievement of key project goals.
Translate experimental data into meaningful insights and present results at team meetings.