Senior Scientist – Cryo-EM

Main Responsibilities

This senior scientist will own cryo-EM structure determination on client programs, from sample and grid optimization through data collection, processing, model building, validation, and deposition. A portion of this scientist’s time will also be spent expressing and purifying recombinant proteins to cryo-EM-grade sample quality, both for their own structures and in support of the broader Protein Sciences group. This is a client-facing role: the successful candidate will write technical reports, present results on project calls, and help scope feasibility for prospective work.

Additional Responsibilities

• Optimize samples and grids for cryo-EM, including buffer, concentration, additive, detergent, and support screening; vitrify using Vitrobot and/or Chameleon.
• Screen grids and collect single-particle datasets on 200 kV and 300 kV instruments (Glacios and Krios class) using EPU and/or SerialEM.
• Process datasets in cryoSPARC and/or RELION, including motion correction, CTF estimation, particle picking, 2D and 3D classification, refinement, and local refinement or symmetry expansion as needed.
• Build, refine, and validate models in Coot, Phenix, and ISOLDE, and prepare and complete EMDB and PDB depositions.
• Express and purify recombinant proteins to cryo-EM-grade quality in support of assigned programs and the broader Protein Sciences group.
• Interface directly with clients: lead scientific update calls, present results, and support feasibility assessment and technical scoping for prospective projects.
• Mentor junior scientists and research associates, and author and maintain SOPs for sample preparation, data collection, and processing.
• The candidate will be responsible for timely updates on project statuses, reporting to their supervisor informally and to Helix’s customers by formal report writing and oral presentations.

Required Qualifications

• Ph.D. in structural biology, biochemistry, biophysics, or a related field with 4 or more years of relevant post-doctoral or industrial cryo-EM experience; OR a Master’s degree with 8–12 years of relevant industrial cryo-EM experience; OR a Bachelor’s degree with 12 or more years of relevant industrial cryo-EM experience.
• Demonstrated independent, hands-on experience taking single-particle cryo-EM projects from sample to final structure with minimal supervision, evidenced by deposited EMDB/PDB entries or an equivalent record of completed structures.
• Hands-on proficiency with grid preparation and vitrification (Vitrobot, Chameleon, or equivalent), including grid screening and sample quality assessment.
• Hands-on experience collecting data on 200 kV and/or 300 kV microscopes (Glacios and Krios class) using EPU and/or SerialEM, including automated session setup and on-the-fly quality monitoring.
• Demonstrated proficiency in single-particle processing using cryoSPARC and/or RELION.
• Demonstrated proficiency in model building, refinement, and validation using Coot, Phenix, and/or ISOLDE, and experience preparing EMDB and PDB depositions.
• Working competency in recombinant protein expression and purification sufficient to generate and troubleshoot cryo-EM-grade samples.
• Demonstrated ability to mentor junior staff and to own project timelines and client-facing deliverables.
• Strong written and oral communication skills, including direct client interaction.

Additional qualifications

• Membrane protein cryo-EM, including detergent screening, nanodisc or SMALP reconstitution, and stabilization strategies.
• GPCR, transporter, ion channel, or other multi-component complex structural work.
• Negative-stain EM for rapid sample triage and construct assessment.
• Microscope alignment, routine instrument troubleshooting, and coordination with service engineers.
• Prior cryo-EM experience in a CRO, biotechnology, or pharmaceutical setting, working to client timelines and specifications.
• Scripting or automation to streamline processing pipelines (Python, shell).
• Exposure to cryo-electron tomography, sub-tomogram averaging, or microED.
• Experience with protein X-ray crystallography as a complementary technique, and familiarity with software such as Phenix, CCP4, Coot, and PyMOL.
• Excellent communication, interpersonal and organizational skills.
• Fearless attitude to tackle longstanding complex problems.