Scientist/Senior Scientist, Spatial Omics in Cells and Tissues

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 is looking for a motivated and talented bench Scientist to join our teams. This role sits at the cutting edge of spatial biology, focusing on mapping the molecular environments of proteins and protein complexes within live and fixed cells and tissues. The successful candidate will lead the development and application of Laser Capture Microdissection (LCM) workflows coupled to a diversity of proximity biotinylation protocols to achieve unprecedented resolution in cellular and tissue-specific multiomics experiments. As a pivotal contributor to our drug discovery and basic research efforts, the successful candidate will contribute to the identification and validation of novel therapeutic targets and biomarkers. This hands-on role requires deep expertise in cell and tissue biology, biochemistry, microscopy and image analysis, alongside the ability to develop or implement novel methods as needed. We are looking for an independent, flexible and proactive scientist, with excellent communication skills, who can manage various studies of high-complexity in a fast-paced environment.

Responsibilities:

• Apply Laser Capture Microdissection (LCM) to isolate specific cell populations or morphological features from cell cultures and tissue sections for downstream multiomics analysis

• Lead the charge, in collaboration with Microscopy and Image Analysis experts, to develop automated image analysis, segmentation, and laser microdissection workflows for increased throughput

• Collaborate with other Technology labs (i.e. Proteomics, Metabolomics, Genomics) to ensure high-fidelity recovery of the relevant molecular entities from microdissected samples

• Design and optimize proximity biotinylation strategies in cells and tissues to map protein-protein interactions (PPIs) in situ

• Optimize and validate delivery vectors and/or CRISPR-based systems to express proximity biotinylation enzymes fused to proteins of interest in relevant biological systems

• Continuously explore this ever-evolving field and invent and/or implement novel systems as they become available

Position Requirements:

• Ph.D. in Cell Biology, Biochemistry, Biophysics, Microscopy, or a related field with 3+ years of post-doctoral or industry experience

• Demonstrated proficiency in Laser Capture Microdissection (e.g. Leica LMD) applications in a diversity of cell and tissue types

• Proven experience with multiplex immunofluorescence and histological techniques, including tissue processing (FFPE and OCT blocks), and cryosectioning

• Comfortable with a variety of fluorescence microscopy systems (i.e. confocal)

• 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 mammalian cell culture and stable cell line generation with a diversity of delivery systems

• Extensive hands-on experience with proximity biotinylation techniques (i.e. BioID, APEX2, TurboID, BAR) applied to cells and tissues, including antibody conjugation strategies, fusion protein design, labeling kinetics optimization, and streptavidin-based enrichment

• 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 diverse functional groups

• Must be willing to work onsite 5 days per week

Nice to Have:

• Experience applying spatial omics workflows to brain samples in the context of neurodegenerative diseases

• Experience working with human tissues and patient-derived samples

• Familiarity with common "spatial-omics" platforms (i.e., 10x Xenium, GeoMx® DSP)

• Familiarity with proteomics, transcriptomics and metabolomics workflows

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.