Senior Scientist, Biochemistry

PacBio•Menlo Park, CA

3d•$128,800 - $193,200•Hybrid

About The Position

PacBio is seeking a Senior Scientist to serve as the protein purification subject-matter expert within the Biochemistry and Reagents R&D group. The role combines creative problem-solving in challenging protein biochemistry with the operational rigor to execute at scale. The Senior Scientist will develop expression, purification, and characterization strategies for difficult and novel nucleic acid–modifying enzymes and their homologs; design quantitative biochemical assays to investigate enzyme function; and build and operate research-scale pipelines, from high-throughput 24- to 96-plex automated preparations to targeted individual purifications. The resulting well-characterized enzymes support PacBio's library preparation and sequencing chemistry research. The Biochemistry R&D group explores enzymes, reaction chemistries, and molecular workflows for third-generation sequencing, testing concepts that may advance into product development. The team combines hands-on biochemistry with sequencing data and collaborates with Bioinformatics, Engineering, and Product teams. The role is onsite Monday through Thursday, with Friday work from home for non-field-based employees; some roles may require 100% onsite work. The employee may also be required to visit and work at other PacBio locations as necessary.

Requirements

PhD in Biochemistry, Molecular Biology, Biophysics, Chemistry, Bioengineering, or a related field, with 2–5 years of relevant post-PhD research experience.
Deep hands-on expertise expressing and purifying recombinant proteins and protein complexes; experience with nucleic acid-binding or nucleic acid-modifying enzymes and troubleshooting difficult targets is ideal.
Expertise using FPLC systems, including affinity, ion-exchange, and size-exclusion chromatography and method development.
Strong foundation in mechanistic enzymology and quantitative biochemical assay development, such as enzyme kinetics, fluorescent or radiolabeled substrate assays, and binding measurements.
Demonstrated experience running high-throughput 24- to 96-plex protein purification on laboratory automation or liquid-handling platforms, such as KingFisher, Tecan, Opentrons, or Hamilton.
Proficiency in protein quality control and characterization, such as SDS-PAGE, capillary electrophoresis, A280 quantitation, DLS, activity assays, and nuclease-contamination assays.
Track record of delivering high-quality reagents while balancing multiple concurrent projects and requests.
Collaborative approach and interest in enabling colleagues across a multidisciplinary group.
Excellent interpersonal, written, and verbal communication skills.
Current authorization to work in the United States without present or future sponsorship.

Nice To Haves

Industry experience is strongly preferred.
Industry R&D experience in biotechnology, life science tools, or enzyme and reagent development, including support for product-development programs or work alongside Manufacturing and Quality teams.
Familiarity with single-molecule biochemistry or biophysics.
Familiarity with DNA sequencing, especially NGS library preparation or long-read sequencing such as PacBio HiFi or Oxford Nanopore.
Experience with biochemical assays for polymerases, ligases, nucleases, or Cas proteins, including enzyme kinetics.
Experience with construct design, molecular cloning, and expression optimization, such as codon optimization, solubility tags, and host selection.
Experience with biophysical characterization methods such as DLS, intact mass spectrometry, and thermal shift.
Structural biology experience, such as X-ray crystallography or cryo-EM, particularly with protein–nucleic acid complexes.
Protein engineering experience, such as site-directed or site-saturation mutagenesis libraries or directed evolution.
Experience analyzing data in Python or R, managing custom databases, and using structure-visualization software such as Chimera, PyMOL, or Coot.

Responsibilities

Build, run, and continuously improve purification pipelines for nucleic acid–modifying enzymes, including polymerases, ligases, nucleases, and Cas proteins, at multiple research scales.
Serve as the group's subject-matter expert on protein expression and purification, advising colleagues on construct design, expression host, affinity tags, and purification strategy.
Develop and compare expression and purification strategies for challenging targets, including poorly soluble proteins, multi-subunit complexes, and novel homologs, to maximize yield, activity, and purity.
Design and execute high-throughput 24- to 96-plex expression and purification campaigns on laboratory automation platforms to screen enzyme variants and homologs in parallel.
Perform targeted individual purifications on ÄKTA FPLC systems using affinity, ion-exchange, size-exclusion, and other chromatography methods.
Design and implement quantitative biochemical assays for new enzyme classes, including steady-state and pre-steady-state kinetics, fidelity, and binding assays; use custom or modified nucleic acid substrates and plate-based activity screens integrated with high-throughput purification.
Establish and run quality control for purified proteins, including purity, concentration, activity, and contaminating nuclease testing, to ensure suitability for library preparation and sequencing chemistry experiments.
Collaborate with scientists across Biochemistry and Reagents R&D to advance new enzymes and homologs from expression through purification and quality control to evaluation in PacBio library preparation and sequencing workflows.
Maintain clear protocols and records, and track inventory of purified enzyme lots.
Mentor and train Scientists and Research Associates in purification and quality-control methods.
Communicate results in team meetings and written reports and contribute to cross-functional discussions.