Who We are:

Calico (Calico Life Sciences LLC) is an Alphabet-founded research and development company whose mission is to harness advanced technologies and model systems to increase our understanding of the biology that controls human aging. Calico will use that knowledge to devise interventions that enable people to lead longer and healthier lives. Calico’s highly innovative technology labs, its commitment to curiosity-driven discovery science, academic and industry partners, and vibrant drug-development pipeline, together create an inspiring and exciting place to catalyze and enable medical breakthroughs.

Position Description:

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.

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

Position 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 Have:

• 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)

The estimated base salary range for this role is $156,000 - $163,000. Actual pay will be based on a number of factors including experience and qualifications. This position is also eligible for two annual cash bonuses.