The posting
Senior Scientist, Biochemistry R&D
PacBio (NASDAQ: PACB) is a premier life science technology company that designs, develops, and manufactures advanced sequencing solutions to help scientists and clinical researchers resolve genetically complex problems. Our mission is to enable the promise of genomics to better human health. Genomics is core to all biological processes, and our advanced genomics tools provide scientists and clinical researchers the insights to better understand biology and health. We are now entering the century of biology and genomics is at the heart of the next revolution. Become part of the new paradigm in gene sequencing and help shape the future of genomic study by joining the PacBio team.
About Biochemistry R&D:
We are PacBio's upstream research engine for third-generation sequencing chemistry and applications. Our team explores new enzymes, reaction chemistries, and molecular workflows, and tests feasibility of ideas that become PacBio's next products. When a concept works, it moves from our bench into Product Development and eventually onto sequencers in labs around the world. Some of our recent work spans HiFi library preparation, targeted enrichment of complex loci, and native detection of DNA modifications. We are a small, rigorous, and curious group. We pair hands-on biochemistry with sequencing data, work closely with Bioinformatics, Engineering, and Product teams, and give scientists real ownership of problems that matter.
Position Summary:
PacBio is seeking a Senior Scientist to serve as the protein purification subject-matter expert within the Biochemistry and Reagents R&D group. This role combines creative problem-solving on 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 that reveal how these enzymes work; and build and operate research-scale pipelines ranging from high-throughput 24- to 96-plex automated preparations to targeted individual purifications. The resulting well-characterized enzymes feed directly into PacBio's library preparation and sequencing chemistry research. The ideal candidate brings deep hands-on expertise in protein purification and mechanistic enzymology, the scientific creativity to solve problems where standard protocols fall short, and a collaborative approach to advancing the work of a multidisciplinary team. Experience applying these skills in an industry R&D environment is strongly preferred.
Responsibilities:
- Build, run, and continuously improve purification pipelines for nucleic acid–modifying enzymes (e.g., polymerases, ligases, nucleases, Cas proteins) at multiple research scales.
- Serve as the group's subject-matter expert on protein expression and purification; advise colleagues on construct design, expression host, affinity tags, and purification strategy.
- Develop expression and purification strategies for challenging targets, including poorly soluble proteins, multi-subunit complexes, and novel homologs, where standard protocols fall short; evaluate alternative strategies side by side to maximize yield, activity, and purity.
- Design and execute 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 on ÄKTA FPLC systems using affinity, ion-exchange, size-exclusion, and other chromatography methods.
- Design and implement quantitative biochemical assays for new enzyme classes (e.g., steady-state and pre-steady-state kinetics, fidelity, and binding), including custom or modified nucleic acid substrates and plate-based activity screens integrated with high-throughput purification.
- Establish and run QC for purified proteins (purity, concentration, activity, and contaminating nuclease testing) so material is fit for use in library preparation and sequencing chemistry experiments.
- Partner with scientists across Biochemistry and Reagents R&D to take new enzymes and homologs from expression through purification and QC to evaluation in PacBio library preparation and sequencing workflows.
- Maintain clear protocols, records, and a tracked inventory of purified enzyme lots.
- Mentor and train Scientists and Research Associates in purification and QC methods.
- Communicate results clearly in team meetings and written reports and contribute to cross-functional discussions.
Required Qualifications:
- PhD in Biochemistry, Molecular Biology, Biophysics, Chemistry, Bioengineering, or a related field, with a minimum of 2–5 years of relevant post-PhD research experience. Industry experience is strongly preferred.
- 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.
- Expert user of FPLC systems with strong command of affinity, ion-exchange, and size-exclusion chromatography and method development.
- Strong foundation in mechanistic enzymology and quantitative biochemical assay development (e.g., enzyme kinetics, fluorescent or radiolabeled substrate assays, binding measurements).
- Demonstrated experience running high-throughput (24- to 96-plex) protein purification on lab automation or liquid-handling platforms (e.g., KingFisher, Tecan, Opentrons, Hamilton).
- Proficiency in protein QC and characterization (e.g., SDS-PAGE, capillary electrophoresis, A280 quantitation, DLS, activity and nuclease contamination assays).
- Track record of delivering high-quality reagents while balancing multiple concurrent projects and requests.
- Consummate team player who enjoys enabling the success of colleagues across a multidisciplinary group.
- Excellent interpersonal, written, and verbal communication skills.
Preferred Experience:
- 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 (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 (e.g., codon optimization, solubility tags, host selection).
- Experience with biophysical characterization methods (e.g., DLS, intact mass spectrometry, thermal shift).
- Structural biology experience (e.g., 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.
- Software Experience: data analysis in Python or R, custom database management and structure visualization (e.g., Chimera, PyMOL, Coot).
Candidates must have current authorization to work in the United States without the need for present or future sponsorship.
Non-Field Based Employees are required to be onsite Monday-Thursday (Friday work from home). Depending on the role, some employees may be required to be 100% onsite.
You may be required from time to time to visit and work at PacBio locations and for such times as the Company considers necessary for the proper performance of your duties.
All listed tasks and responsibilities are deemed as essential functions to this position; however, business conditions may require reasonable accommodations for additional tasks and responsibilities.
All qualified applicants will receive consideration for employment without regard to race, sex, color, religion, national origin, protected veteran status, or on the basis of disability, gender identity, and sexual orientation.
#LI-Onsite
Salary Range:
$128,800.00 - $193,200.00
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