Senior Scientist – Protein Production

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 protein production to join our Indianapolis-based team. Main Responsibilities This senior scientist will own recombinant protein production campaigns end-to-end, from construct design through expression, purification, and final quality control. The role spans multiple hosts and cell lines — bacterial, insect, mammalian, and yeast — and the full purification toolkit, with particular responsibility for the difficult targets that do not respond to standard approaches. As a senior member of the team, this scientist will mentor junior staff, author and maintain protocols and SOPs, own delivery timelines, and interface directly with clients on strategy, progress, and results. Highly desirable hands-on experiences include: (a) Deep hands-on expression experience across multiple hosts and cell lines — E. coli , insect/baculovirus (Sf9, High Five), mammalian (HEK293, CHO), and yeast (Pichia, S. cerevisiae ) — including transient expression, stable pools, small-scale condition screening, and scale-up. (b) Deep hands-on purification experience across affinity and IMAC, ion exchange, size exclusion, and hydrophobic interaction chromatography, together with tag removal, refolding, and membrane protein solubilization and detergent screening. We are looking for a protein scientist who has already solved hard targets and can judge quickly which lever to pull next — construct boundaries, host, temperature, media, tags, fusion partners, chaperones, detergent, or refolding. The successful candidate will run several campaigns in parallel, hold a high bar on QC and documentation, and communicate honestly with clients and the HBS team about what is achievable and by when. Prior industrial experience is strongly preferred: this is a service business, and timelines, reproducibility, and client communication carry the same weight as yield. Additional Responsibilities Design constructs and production strategies for new targets, including boundary selection, tag and fusion partner choice, codon optimization, and host selection. Execute and troubleshoot expression across bacterial, insect, mammalian, and yeast systems, including transient transfection, stable pool generation, and cell-free expression where appropriate. Run small-scale expression and condition screens, then scale up through shake flask, wave, and bioreactor formats, optimizing media, induction, and harvest conditions. Develop and execute purification strategies using affinity and IMAC, ion exchange, size exclusion, hydrophobic interaction, and other chromatographic methods, including tag removal, refolding, and complex reconstitution. Solubilize and purify membrane proteins, including detergent and amphiphile screening and reconstitution into nanodiscs or other supports. Perform and interpret QC by SDS-PAGE, analytical SEC, mass spectrometry, A280, and endotoxin testing, and deliver material to defined specifications for structural, biophysical, and functional studies. Own campaign timelines: plan resource needs, flag risk early, and keep client-facing milestones on schedule. Interface directly with clients: participate in kickoff and scientific update calls, present results, and support technical scoping and feasibility discussions for prospective projects. Mentor junior scientists and research associates, and author, review, and maintain protocols and SOPs. 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 biochemistry, biophysics, molecular biology, protein engineering, or a related field with 4 or more years of relevant post-doctoral or industrial experience; OR a Master’s degree with 8–12 years of relevant industrial experience; OR a Bachelor’s degree with 12 or more years of relevant industrial experience. Demonstrated independent competency in recombinant protein expression across at least three of the following: coli , insect/baculovirus (Sf9, High Five), mammalian (HEK293, CHO), and yeast (Pichia, S. cerevisiae ). Demonstrated competency in transient expression and stable pool generation, small-scale screening, and scale-up through shake flask and bioreactor or wave formats, including media and condition optimization. Demonstrated purification depth across affinity and IMAC, ion exchange, size exclusion, and hydrophobic interaction chromatography, including tag removal and AKTA-based method development. Hands-on experience with difficult targets: low-yield, unstable, aggregation-prone, multi-component, and/or membrane proteins, including refolding and detergent screening. Ability to generate and characterize milligram-to-gram quantities of high-quality protein reagents for downstream structural, biophysical, and functional studies. Experience with standard analytical and biophysical QC (SDS-PAGE, analytical SEC, mass spectrometry, A280, endotoxin) and with setting and defending release specifications. Demonstrated ability to mentor junior staff, author protocols and SOPs, and own delivery timelines. Strong written and oral communication skills, including direct client interaction. Additional qualifications Prior industrial experience in a biotechnology or pharmaceutical company, or in a CRO or CDMO, is strongly preferred. Experience running multiple client-facing production campaigns in parallel to fixed timelines and specifications. Cell-free expression systems. Endotoxin-aware and low-endotoxin production workflows for cell-based and in vivo applications. Protein engineering and/or design approaches to improve expression, solubility, and stability. Antibody, Fab, VHH, and other biologics production and purification. Structural biology experience (X-ray crystallography or Cryo-EM), including preparing samples to structure-grade quality. Molecular biology workflows: molecular cloning, site-directed mutagenesis, vector design, and baculovirus generation. Experience with laboratory inventory, LIMS, or electronic lab notebook (ELN) systems, and with cell bank management. 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.