Scientist – Biophysical Characterization

Helix Bio Structures, 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.

This scientist will run our biophysical characterization work streams 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 biophysical studies.

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.

• 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.