Scientist – Biophysical Characterization

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 Scientist focused on biophysical characterization to join our Indianapolis-based team. Main Responsibilities This scientist will run our biophysical characterization workstreams across a broad technique stack, designing and executing experiments that define the purity, homogeneity, oligomeric state, stability, and binding behavior of client proteins and their ligands. The role covers method development, assay qualification and QC, and the analysis and interpretation that turn raw data into a defensible client recommendation. A portion of this scientist’s time will also be spent expressing and purifying the recombinant proteins that feed their own biophysics work. This is a client-facing role: the successful candidate will write technical project reports and present and defend results on client calls. Highly desirable hands-on experiences include: (a) Multi-technique biophysical characterization of proteins and protein–ligand interactions, including several of SPR, BLI, ITC, MST, DSF/nanoDSF, SEC-MALS, DLS, AUC, CD, Mass Photometry, and SAXS. (b) Recombinant protein expression and purification across bacterial, insect, and/or mammalian systems to the quality required for quantitative biophysics. Breadth matters more than depth on any single instrument in this role. The successful candidate will be fluent across several orthogonal techniques, will choose the right one for the question at hand rather than defaulting to a favorite, and will know how to distinguish a real signal from an artifact. This scientist will work independently at the bench, design sound experiments with appropriate controls and replicates, and produce data and analysis of a quality we can put in front of a client without rework. Any structural biology experience (X-ray crystallography or Cryo-EM) is a welcome plus but is not required for this role. Additional Responsibilities Design and execute biophysical characterization plans that answer specific client questions about purity, homogeneity, oligomeric state, stability, binding, and cooperativity. Determine binding affinities and kinetics by SPR, BLI, ITC, and/or MST, including assay design, surface and sensor chemistry, reference and control strategy, and regeneration assessment. Assess protein stability and formulation behavior by DSF/nanoDSF, thermal and chemical denaturation, DLS, and related methods. Characterize size, mass, and oligomeric state by SEC-MALS, mass photometry, analytical ultracentrifugation, and/or native mass spectrometry. Support fragment and hit validation campaigns, including orthogonal confirmation and triage of screening actives. Develop, qualify, and troubleshoot new assays and methods, and establish and maintain assay QC and instrument performance standards. Express and purify recombinant proteins to support assigned biophysics projects and the broader Protein Sciences group. Analyze and interpret data, prepare figures, write technical project reports, and present results to clients on scientific update calls; support technical scoping of prospective work. 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; OR a Master’s degree with 2–5 years of relevant industrial experience; OR a Bachelor’s degree with 5–10 years of relevant industrial experience. Demonstrated hands-on competency across multiple biophysical techniques, with independent experience on at least three of the following: SPR, BLI, ITC, MST, DSF/nanoDSF, SEC-MALS, DLS, AUC, CD, Mass Photometry, or SAXS. Demonstrated ability to determine binding affinities and kinetic constants and to defend the resulting numbers, including appropriate controls, replicates, and error analysis. Hands-on experience with recombinant protein expression and purification sufficient to generate the material required for their own biophysical studies. Experience with standard analytical techniques for assessing protein quality, purity, and stability (e.g., SDS-PAGE, SEC, Mass spectrometry, UV/Vis spectroscopy). Demonstrated method development and troubleshooting ability, rather than execution of fixed protocols alone. Strong data analysis, curve fitting, and scientific judgment. Strong written and oral communication skills, including comfort in presenting data directly to clients. Additional qualifications Hydrogen–deuterium exchange mass spectrometry (HDX-MS) or native mass spectrometry. SAXS data collection, processing, and interpretation, including synchrotron beamline experience. Fragment-based screening by SPR, DSF, NMR, or MS, and orthogonal hit validation strategies. Membrane protein biophysics, including detergent, nanodisc, and stability screening. Antibody and biologics characterization, including epitope binning and developability assessment. Enzymology and activity assay development. Scripting or statistical analysis (Python, R, GraphPad Prism) for data reduction and curve fitting. Prior experience in a CRO, biotechnology, or pharmaceutical setting, working to client timelines and specifications. Exposure to structural biology (X-ray crystallography or Cryo-EM) is a plus but not required. 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.