Neurodegenerative diseases are one of the largest medical challenges of our time. Denali Therapeutics is a biotechnology company based in South San Francisco, California that is dedicated to defeating neurodegenerative diseases through rigorous therapeutic discovery and development. Denali is founded on the collaboration of leading scientists, industry experts, and investors who share the vision that scientific discovery energetically applied to translational medicine is the key to delivering effective therapies to patients.


The Opportunity:

Denali is continuing to build a leading, innovative Discovery organization that will strongly contribute to the discovery and development of novel therapeutics for neurodegenerative diseases. We are currently seeking excellent candidates to join our Discovery team based at our headquarters in South San Francisco, California.

The candidate for this senior position will be responsible for leading the production efforts of large molecule biotherapeutics, across the discovery-to-development stages, to support the identification and characterization of novel therapeutics for the treatment of neurodegenerative diseases.  Under minimal supervision, the Principal Scientist for this position will independently design and implement production and purification strategies for complex engineered antibodies, Fc-fusions and bioconjugated therapeutics.  Working with multiple groups across Denali, he/she will generate highly characterized proteins, from the milligram to gram scale, to enable in vitro and in vivo studies and to support development efforts.  You will be expected to design, perform and oversee experiments, mentor colleagues, analyze and interpret results, coordinate appropriate CRO activities (including both routine and complex protein production), organize and carefully document results, and communicate findings.

We seek candidates with extensive experience in generating antibodies, antibody-drug conjugates (or bioconjugations), and/or engineered Fc-fusions, across the discovery-to-development stages.  Close collaboration with protein engineers, pharmacologists, biologists & CMC teams will be essential to success.



  • Design, implement & optimize purification and production strategies for large molecule biotherapeutics, including engineered antibodies (and other IgG-like molecules), bioconjugations and engineered Fc-fusions
  • Purify large molecule therapeutics from cell culture (i.e. CHO/293) by column chromatography using AKTA systems, and design and transition to scalable processes, up to gram quantities
  • Lead troubleshooting efforts for protein expression and purification processes
  • Analyze proteins using standard protein characterization methods (including HPLC, SEC-MALS, CE-SDS, DLS, DSF, MCE and others)
  • Guide the development and implementation of fit-for-purpose analytics that support development 
  • Support hit generation and lead optimization activities for multiple large molecule targets
  • Assist in identifying lead therapeutic candidate molecules based on purification & analytical workflows
  • Think creatively about ways to integrate novel protein modalities with our blood-brain-barrier (BBB)-crossing technologies
  • Actively contribute to project teams and work effectively across functional teams to help advance programs to development


Successful candidates will meet most of these criteria:

  • PhD in Biochemistry or related scientific discipline with 12+ years in biotech/biopharma industry or M.Sc/B.Sc. with ≥15 years of experience in biotech/biopharma
  • Extensive experience in biotherapeutic protein production and biochemistry, as reflected in authorship on peer-reviewed publications
  • Experience in the generation and development of antibody-drug conjugates and/or other bioconjugated materials
  • In-depth experience in the purification of challenging and/or engineered proteins
  • Experience working with CROs for the production of routine and complex proteins
  • Extensive knowledge and hands-on experience with large molecule protein purification workflows including multiple chromatographic methods (immunoaffinity, IEC, HIC, SEC)
  • Experience in molecular biology, including construct design
  • Excellent oral, presentation and written communication skills are required
  • Creative thinker with a strong sense of responsibility and a desire to collaborate in an exciting and fast-paced research environment


Denali is committed to its core company value of unity by creating a diverse and inclusive environment.  We are proud to be an equal opportunity employer and do not discriminate against any employee or applicant for employment because of race, color, sex, age, national origin, religion, sexual orientation, gender identity and/or expression, status as a veteran, basis of disability, or any other federal, state or local protected class.


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