Scientist, Biochemical Assays

Calico•South San Francisco, CA

2d•$156,000 - $163,000•Onsite

About The Position

The Cellular Models and Assay Technologies (CMAT) group at Calico is seeking a talented and creative bench Scientist to lead the design, optimization, and implementation of complex biochemical assays to support our drug discovery efforts. As an expert individual contributor, the successful candidate will perform advanced hands-on laboratory work while also managing external Contract Research Organizations (CROs) to scale our capabilities. The position requires the candidate to have extensive experience in enzymology, in vitro pharmacology, and the biophysical characterization of protein-ligand interactions. In this role, you will act as a thought leader, driving innovative assay technologies to advance therapeutic pipelines and developing novel approaches for the mechanistic elucidation of hit compounds. You will serve as a key technical lead on project teams, integrating early research data to progress programs from target validation through to lead optimization. As such, the ideal candidate will be intellectually and technically nimble, quantitative, collaborative, well-organized, and capable of quickly grasping the fundamentals of new biological systems.

Requirements

PhD in Biochemistry, Biophysics, Pharmacology, or a related field, plus 3+ years of industry experience in biochemical assay development within a pharmaceutical or biotechnology setting
Extensive knowledge of steady-state kinetics, enzyme inhibition modes, and the quantitative analysis of protein-ligand interactions with demonstrated ability to apply these principles to elucidate mechanism of action, kinetics, and thermodynamics
Proven track record of designing and validating assays using diverse readouts (TR-FRET, AlphaLISA, FP, Luminescence, Mass Spec) and implementing them on laboratory automation platforms (Echo, Bravo, Hamilton)
Advanced quantitative skills with the ability to analyze kinetic data using specialized software (GraphPad Prism, Genedata, CDD, Python, R) and communicate these findings clearly to interdisciplinary teams
Demonstrated experience identifying, onboarding, and overseeing scientific work at external contract research organizations to ensure high-quality data generation
Excellent oral and written communication skills; detail-oriented, organized, flexible, and capable of multitasking in a fast-paced environment
Must be willing to work onsite five days per week

Nice To Haves

Experience with orthogonal assay formats, including cell-based assays, complex media (lysates, lipid vesicles), or biophysical assays (SPR, DSF/TSA)
Hands-on experience with protein design, expression, and purification from various systems
Familiarity with microfluidics-based assays or High-Throughput Mass Spectrometry (e.g., RapidFire, SAMDI)
Experience with Fragment-Based Drug Discovery (FBDD) or Targeted Protein Degradation (TPD) assay formats (ternary complex formation)

Responsibilities

Lead protein-based assay development, designing and executing complex assays (enzymatic, PPI, protein-nucleic acid) utilizing diverse readouts (Luminescence, TR-FRET, AlphaLISA, FP) and advanced technologies (mass spectrometry, microfluidics) to interrogate novel biological targets
Go beyond routine screening to serve as a thought leader on assay strategy and mechanistic characterization and apply rigorous enzymological and biophysical principles to elucidate mechanism of action, kinetics, and thermodynamics of ligand-target interactions
Serve as a key technical lead on cross-functional teams, partnering with medicinal and computational chemists to drive Structure-Activity Relationship (SAR) cycles
Interpret complex biological data to guide compound design and progress programs from target validation through to lead optimization
Oversee the transition of bench-scale assays to automated high-throughput formats, ensuring statistical rigor (Z-factor), miniaturization, and seamless integration with laboratory automation for large-scale campaigns
Identify, qualify, and manage CRO partners for assay transfer and routine screening; ensure external data quality matches internal standards to support the pipeline