Senior Scientist, Biochemistry

Pacific Biosciences•Menlo Park, CA

1d•Onsite

About The Position

PacBio is seeking a Senior Scientist to serve as the protein purification subject-matter expert within its Biochemistry and Reagents R&D group. The role combines creative problem-solving in challenging protein biochemistry with the operational rigor needed to execute at scale. The Senior Scientist will develop strategies to express, purify, and characterize 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 automated 24- to 96-plex preparations to targeted individual purifications. The resulting characterized enzymes support research into PacBio library preparation and sequencing chemistry. Biochemistry R&D explores enzymes, reaction chemistries, and molecular workflows for third-generation sequencing chemistry and applications. The group works with sequencing data and collaborates with Bioinformatics, Engineering, and Product teams. The position is suited to someone with deep hands-on expertise in protein purification and mechanistic enzymology, scientific creativity, and a collaborative approach. Industry R&D experience is strongly preferred. Non-field-based employees are required to work onsite Monday through Thursday, with Friday work from home. Some roles may require employees to be onsite 100% of the time. The employee may also be required to visit and work at PacBio locations as necessary. Candidates must currently be authorized to work in the United States without present or future sponsorship.

Requirements

PhD in Biochemistry, Molecular Biology, Biophysics, Chemistry, Bioengineering, or a related field.
A minimum of 2–5 years of relevant post-PhD research experience.
Deep hands-on expertise expressing and purifying recombinant proteins and protein complexes, ideally nucleic acid–binding or nucleic acid–modifying enzymes, including troubleshooting difficult targets.
Expertise with FPLC systems and strong command of 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 conducting high-throughput 24- to 96-plex protein purification using lab automation or liquid-handling platforms.
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 managing 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 the need for present or future sponsorship.

Nice To Haves

Industry R&D experience in biotechnology, life science tools, or enzyme and reagent development, including supporting product development programs or working 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, and/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 with data analysis in Python or R, custom database management, and 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 hosts, affinity tags, and purification strategies.
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.
Run high-throughput 24- to 96-plex expression and purification campaigns on lab automation platforms to screen enzyme variants and homologs in parallel.
Perform targeted individual purifications using ÄKTA FPLC systems and affinity, ion-exchange, size-exclusion, and other chromatography methods.
Design and implement quantitative biochemical assays for new enzyme classes, including kinetics, fidelity, and binding assays, 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 material is suitable for library preparation and sequencing chemistry experiments.
Partner with scientists across Biochemistry and Reagents R&D to advance 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.