Senior Principal Scientist, Structural Biology Full-time

Senior Principal Scientist, Structural Biology

Facility: Research

Location: Lexington, MA, US

About the Department

Our Research & Development organization brings together the best minds in life science innovation. The teams located in facilities in Lexington, Watertown, Cambridge and Seattle reflect the full R&D continuum, from early research through late-stage clinical development. Here, we are building for the future, creating a distinct R&D community based on collaboration, partnerships, and cutting-edge research across multiple modalities and therapeutic areas. We recognize that improving human health starts here and that patients rely on us. Our R&D hub merges biotech speed and agility with large pharmaceutical company quality, resources, and stability, uniting the best of both worlds to develop new medicines for patients.

The Position

We are seeking a highly skilled and motivated structural biologist with extensive experience working in a pharmaceutical industry setting. The Senior Principal Scientist – Structural Biology will be responsible for leading and managing our structural biology activities to solve protein-small molecule ligand complex structures for drug discovery projects within the Small Molecule Research (SMR) unit at Novo Nordisk (NN), leveraging a highly outsourced CRO model, and also supporting external collaborations.

Responsibilities include: Designing suitable structural biology strategies (crystallography and cryo-EM) for multiple small molecule projects; proposing and overseeing construct design, expression and purification of proteins, crystallization, cryo-grid preparation and evaluation; collaborating within a cross-functional project team to improve understanding of mechanism of action (MoA) of lead compounds; work collaboratively through interactions across therapeutic areas (TAs) within NN; managing a number of contract research organizations (CRO) across the globe; supporting the preparation of patents, reports, scientific publications, and serving as functional expert in supporting IND filings.

Relationships

Reports to Director Small Molecule Biochemistry and Biophysics, Novo Nordisk (NN) Small Molecule and Cross Modality Research (SMCMR) Unit, in Therapeutics Discovery (TD).

Will interact and closely collaborate with other Small Molecule Research unit scientists (medicinal chemists, biochemists, biophysicists), other members of Therapeutics Discovery, Data Science & Innovation (DSI) computational chemists, D&O (Diabetes & Obesity) biology, Cardiovascular & Renal (CVRD) biology, Rare Disease (RD) biology, Drug Metabolism and Pharmacokinetics (DMPK), cellular biology, pharmacology, toxicology and translational medicine teams globally.

Will interact on a constant basis with structural biology CROs globally.

Essential Functions

• Responsible for designing the overall structural biology strategy for multiple small molecule research projects
• Deliver and interpret structures and collaborate with cross-functional project teams to enable structure-based drug design and elucidate the mechanism-of-action of small molecules
• Oversee construct design, expression and purification of proteins for structure determination at CROs
• Develop protocols to obtain high quality crystals for X-ray structures
• Develop protocols for grid optimization, data collection, and data analysis for structure determination using cryo-EM
• Obtain and refine structures of protein-ligand complexes, communicate the results and collaborate with project teams to drive hit-to-lead and lead optimization

• Has accountability for CROs timelines, activities and data quality
• Establish and maintain strong productive relationships with strategic partners and collaborators

• Independent contributor to internal drug discovery activities
• Serve as a trusted expert in structural biology

Qualifications

• Master's degree with 16+ years of relevant experience, or PhD with 12+ years of relevant experience required
• 8+ years of structural biology industry experience preferred
• 3+ years of previous experience managing CROs preferred
• 3+ years of structural biology work in a hybrid model preferred
• In-depth knowledge and hands-on experience in X-ray crystallography and cryo-EM, including crystal optimization, grid preparation, data collection, data processing, structure refinement, and interpretation of protein structures using internal and external (CRO) resources
• Extensive knowledge and experience in protein production including construct design/protein engineering, protein expression systems (bacterial, insect, mammalian systems), protein purification techniques and protein characterization methods
• Experience in membrane protein production and structure determination highly desirable

• Experience with other structural methods such as HDX-MS and SAXS a plus.

• Familiarity with in vitro biochemical and biophysical methods such as SPR, FP, FRET, ITC, DSF, MST, MS and their application to structure activity relationships
• Well-versed in data processing and refinement software for structure determination and analysis

• Demonstrated track record of supporting high-quality structure determination and validation of protein co-complexes across disease areas using in-house and/or CRO resources to rapidly advance drug discovery pipelines
• Careful attention to details; Maintain detailed documentation
• Experience in writing IND reports and scientific papers
• Experience enhancing operational efficiency and implementing best practices within line of business (LoB)
• A clear track record of innovation and impact on programs as evidenced by patents and peer-reviewed publications
• Demonstrates excellent verbal and written communication skills, strong interpersonal skills with a demonstrated ability to work collaboratively on multidisciplinary teams
• Proficient in Microsoft Office suite of products (Outlook, Excel, Word, PowerPoint)