Senior Scientist – Cryo-EM

Helix BioStructures, LLC (HBS) is a contract research organization based in Indianapolis, Indiana, providing early drug discovery services to the biopharmaceutical industry. HBS maintains a full suite of services that encompass chemical & structural analysis, protein production, computational modeling, and design. HBS’s core and most popular services are structural biology imaging techniques: X-ray Crystallography and Cryo-EM. HBS was founded in 2018 and has grown considerably. We are looking to add a Senior Scientist focused on cryo-EM to join our Indianapolis-based team. 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. Highly desirable hands-on experiences include: (a) Independent, end-to-end single-particle cryo-EM: vitrification and grid optimization, screening and automated data collection, processing, model building, refinement, validation, and EMDB/PDB deposition. (b) Recombinant protein expression and purification to cryo-EM-grade sample quality, including multi-component complexes and detergent- or nanodisc-solubilized targets. We are looking for someone who can run the cryo-EM pipeline from day one with minimal training on our side. The successful candidate will have already taken multiple structures from sample to deposited coordinates independently, will exercise sound judgment about when a sample, grid, or dataset is worth pushing forward, and will be comfortable explaining those decisions directly to clients. As a senior member of the team, this scientist will mentor junior staff, set technical standards, and help shape how we scope and execute cryo-EM projects. Overall, you will be an outstanding structural biologist and collaborator with a significant and visible impact on our client portfolio. 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. Location This position is based in Indianapolis, Indiana, and does NOT offer a hybrid option. Interaction with external service vendors is also expected. Physical Requirements Able to lift 30 lb objects with dimensions 30 inches in height and 18 inches in width. Able to visualize microscopic objects under microscopes. Non-standard work schedule, travel, and lab safety Able to adhere to safe work practices and perform lab work with appropriate personal protective equipment such as but not limited to safety goggles, facial mask, gloves, lab coat/ protective gowning, and closed-toe shoes. Able to work at flexible hours occasionally when performing time-sensitive experiments. Other job details Eligible for Relocation Package Retirement (matching 401K) Health/Dental/Vision Insurance Company Apple computer Helix BioStructures, LLC is an equal opportunity employer, and we embrace the increasingly diverse world around us. Helix BioStructures, LLC prohibits unlawful discrimination based on race, color, religion, gender, sexual orientation, gender identity or expression, national origin or ancestry, age, disability, marital status, and veteran status.