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) lab and Microscopy group at Calico are looking for an innovative, technology-driven Scientist to join our teams. This role offers a rare chance to push the boundaries of microscopy and spatial biology within a biotech environment, where novel technologies can be rapidly translated into biological insights that directly inform therapeutic strategy. In collaboration with Biology subject matter experts, the successful candidate will invent, adapt, and apply advanced microscopy techniques to unravel the mechanisms underlying age and age-related disease. A primary area of focus will be the integration of Laser Capture Microdissection (LCM) with proximity biotinylation, in order to map molecular environments within cells and tissues. By combining these with fluorescent biosensors and morphological profiling, you will aim to identify and isolate specific cellular states for deeper phenotyping. 

This hands-on role requires deep expertise in Microscopy, Image Analysis, Cell and Tissue Biology, alongside the ability to develop or implement novel methods as needed. This role will evolve as scientific questions demand, and we are looking for a curious, versatile and proactive scientist who takes an active role in the evolution and expansion of their role. 

Responsibilities:

• In collaboration with other Microscopy and Image Analysis experts, deploy cutting edge technologies to accelerate diverse projects across Calico
• Apply Laser Capture Microdissection (LCM) to isolate specific cell populations or morphological features from cell cultures and tissue sections for downstream multiomics analysis
• Accelerate LCM workflows through automated image analysis and segmentation
• Design and optimize functional reporters in cells and tissues, e.g. proximity biotinylation, to map protein-protein interactions, and fluorescent biosensors to track cellular response to perturbation
• Continuously explore this ever-evolving field and invent and/or implement novel systems as they become available

Position Requirements:

• Ph.D. in Cell Biology, Bioengineering, Biophysics, or a related field with 3+ years of post-doctoral or industry experience
• Extensive hands-on experience with complex fluorescence microscopy techniques (e.g. laser capture microdissection, smart microscopy, light sheet, live cell imaging, super-resolution, etc.)
• Track record of developing or adapting novel microscopy methods to uncover biological insights
• Demonstrated ability in quantitative image analysis, utilizing commercial software (e.g., Imaris, Arivis), open-source tools (e.g., FIJI, CellProfiler), and custom solutions (e.g., Python)
• Experience with functional reporter systems in cells and/or tissues (e.g., proximity biotinylation, fluorescent biosensors) and demonstrated ability to rapidly adopt new techniques
• Experience with mammalian cell culture and stable cell line generation with a diversity of delivery systems
• Ability to operate independently, define experimental strategies, and prioritize multiple concurrent projects in a fast-paced environment
• Exceptional interpersonal and communication skills and effective collaboration across functional groups
• Must be willing to work onsite 5 days per week

Nice to Have:

• Demonstrated proficiency in Laser Capture Microdissection (e.g. Leica LMD) applications in a diversity of cell and tissue types
• Hands-on experience with proximity biotinylation techniques (i.e. BioID, APEX2, TurboID, BAR), including antibody conjugation strategies, fusion protein design, labeling kinetics optimization, and streptavidin-based enrichment
• Hands-on experience with development, optimization, and application of fluorescent sensors and biosensors
• Familiarity with custom microscope hardware and control software
• Experience with complex cell culture models (e.g. primary culture, iPSC-derived neurons, microglia)
• Experience with multiplex immunofluorescence and histological techniques, including tissue processing (FFPE and OCT blocks), cryosectioning, human tissues and patient-derived samples

The estimated base salary range for this role is $156,000 - $191,000. Actual pay will be based on a number of factors including experience and qualifications. This position is also eligible for two annual cash bonuses.

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, and, with academic and industry partners, its vibrant drug-development pipeline, together create an inspiring and exciting place to catalyze and enable medical breakthroughs. 

Position Description: 

We are seeking an innovative Principal Scientist to bridge the gap between traditional antibody discovery and cutting-edge computational design. In this role, you will serve as the primary scientific liaison between wet-lab antibody team and our machine learning engineers, driving the evolution of our "Design-Build-Test-Learn" cycle.

Acting as both a project leader and technical expert, you will translate complex in silico designs into actionable experimental workflows. You will be responsible for ensuring that computational predictions are rigorously validated and that the resulting biological data is structured to retrain and refine our internal models. We are looking for a deep expert in therapeutic antibody development who is eager to move beyond traditional random screening and champion a rational, data-driven approach to biologic drug discovery.

Position Requirements:

• Ph.D. in molecular biology, biochemistry, computational modeling, structural biology, or related discipline
• 8+ years’ post-PhD experience in antibody/protein engineering within the biotech or biopharma industry
• Demonstrated ability to work intimately with data scientists and ML engineers and able to articulate biological constraints (e.g., immunogenicity, manufacturability) to computational teams and interpret their in silico outputs for experimental validation
• Hands-on proficiency with structural modeling and extensive knowledge in ML protein design tools
• Experience designing experiments specifically to generate high-quality training data for ML models (e.g., focused libraries, systematic mutagenesis) is highly desirable
• Extensive experience in rational design for humanization, affinity/specificity optimization, pH-dependence, and liability removal
• Experience in engineering multi-specific antibodies
• Strong understanding of biophysical characterization to ensure designed molecules are developable therapeutics
• Experience technically managing CROs for in vivo and in vitro discovery of antibodies, gene synthesis, protein production, and screening assays
• Ability to propose novel scientific approaches and solve complex technical hurdles independently
• Must be willing to work onsite 5 days a week

The estimated base salary range for this role is $198,000 - $241,000. Actual pay will be based on a number of factors including experience and qualifications. This position is also eligible for two annual cash bonuses.