Mass Spectrometry Postdoctoral Researcher - Zhou Lab

Buck Institute for Research on Aging; Novato (CA); On-site; USD 70,000 - 110,000; Full time

Job summary

The Buck Institute for Research on Aging is seeking a hands-on mass spectrometry scientist or postdoctoral researcher to establish a structural-MS platform and lead instrument operation, method development, and data interpretation.

Experience in native MS, crosslinking MS, HDX-MS, or intact-protein/top-down analysis is preferred. This role offers collaboration with protein biochemists, structural biologists, and computational researchers in Novato, CA.

Qualifications

• PhD in analytical chemistry, biochemistry, biophysics, structural biology, or related discipline. Experienced master's-level applicants with substantial instrument-operation and method-development experience may be considered for staff.
• Hands-on operation of a high-resolution mass spectrometer, including setup, performance assessment, and troubleshooting.
• Substantial practical expertise in native MS, crosslinking MS, HDX-MS, or intact-protein/top-down MS.
• Experience connecting sample preparation, acquisition settings, data analysis, and experimental controls to reliable conclusions.
• Strong scientific reasoning, careful documentation, and ability to work independently and collaboratively.

Responsibilities

• Establish, optimize, and run structural-MS workflows, including low-flow LC for bottom-up proteomics and crosslinking, and LC workflow for intact-protein/native MS.
• Develop native-MS and/or crosslinking-MS methods to characterize protein-complex composition, stoichiometry, interactions, and structural changes.
• Prepare and evaluate samples, including buffer exchange, desalting, crosslinking, digestion, and enrichment; optimize native SEC or buffer exchange while assessing sample integrity.
• Optimize ionization, ion transmission, precursor isolation, and fragmentation for heterogeneous proteins; troubleshoot and coordinate maintenance with vendor specialists.
• Establish QC standards, reproducible protocols, and workflows for increased throughput, including batch QC and switching between native and denaturing analyses.
• Analyze spectra with controls, uncertainty assessment, and validation; distinguish solution-state interactions from artifacts and assess crosslinks and PTMs.
• Maintain clear experimental records and organize raw data and protocols.
• Collaborate on experimental design, train colleagues, and contribute to publications and consortium deliverables.

Skills

Hands-on MS operation

Data interpretation

Independent work

Collaborative skills

Education

PhD in analytical chemistry

Tools

High-resolution mass spectrometer

LC-MS system

Job description

Overview

The laboratory of Dr. Kai Zhou at the Buck Institute for Research on Aging seeks a hands-on mass spectrometry scientist or postdoctoral researcher to establish and operate a structural mass spectrometry platform. We welcome candidates with expertise in native mass spectrometry, crosslinking mass spectrometry, HDX-MS, or intact-protein/top-down analysis.

Our laboratory investigates how protein structure, interactions, and assembly change with aging and disease. Projects include intrinsically disordered proteins (IDR/IDPs), protein complexes, and ribosomes.

The successful candidate will take substantial ownership of instrument operation, method development, data quality, and biological interpretation. The role offers opportunities to develop new workflows and pursue scientific questions in collaboration with protein biochemists, structural biologists, and computational researchers.

Responsibilities

• Establish, optimize, and run structural-MS workflows, including low-flow LC for bottom-up proteomics and crosslinking, and a separate LC workflow for intact-protein and native MS analysis.
• Develop native-MS and/or crosslinking-MS methods to characterize protein-complex composition, stoichiometry, interactions, and structural changes. Explore intact-complex analysis and complex-down MS workflows where experimentally feasible.
• Prepare and evaluate samples, including buffer exchange, desalting, crosslinking, digestion, and enrichment as appropriate; optimize native SEC or rapid online buffer exchange while assessing sample integrity and complex stability.
• Optimize ionization, ion transmission, precursor isolation, and fragmentation for heterogeneous proteins and assemblies; assess instrument performance, troubleshoot problems, and coordinate maintenance and training with vendor specialists.
• Establish quality-control standards, reproducible protocols, and reliable workflows for increasing sample throughput, including automated or unattended acquisition, batch QC, carryover checks, and reproducible switching between native and denaturing analyses.
• Analyze and interpret spectra with appropriate controls, uncertainty assessment, and validation; distinguish solution-state interactions from source-induced dissociation or adducts and assess crosslink identifications and proteoform/PTM assignments as appropriate.
• Maintain clear experimental records and organize raw data, analysis files, and protocols.
• Collaborate on experimental design, train colleagues, and contribute to publications and consortium deliverables.

Required

• PhD in analytical chemistry, biochemistry, biophysics, structural biology, or a related discipline. Experienced master’s-level applicants with substantial independent instrument-operation and method-development experience may be considered for an appropriate staff appointment.
• Demonstrated hands-on operation of a high-resolution mass spectrometer, including acquisition-method setup, performance assessment, and troubleshooting.
• Substantial practical expertise in at least one of the following: native MS, crosslinking MS, HDX-MS, or intact-protein/top-down MS.
• Experience connecting sample preparation, acquisition settings, data analysis, and experimental controls to reliable conclusions.
• Strong scientific reasoning, careful documentation, and the ability to work independently and collaboratively.

Preferred

• Native electrospray, native MS, intact-protein/top-down or complex-down analysis, or multistage fragmentation.
• Crosslinker selection, reaction optimization, enrichment, crosslinked-peptide identification, and false-discovery-rate assessment.
• Recombinant protein purification, sample-integrity assessment, and troubleshooting aggregation or heterogeneity.
• Analysis of disordered proteins, heterogeneous assemblies, or ribonucleoprotein complexes.
• Workflow automation, quantitative analysis, or scripting for reproducible data processing; familiarity with crosslinking or proteoform-analysis software. Experience supporting complementary bottom-up proteomics or metabolomics applications is also welcome.

Candidates need not have experience in every listed technique. We value demonstrated depth, ownership, and the ability to learn complementary approaches.