Sr. Research Associate, Structural Biology

Discovery Biology · San Diego, California
Department Discovery Biology
Employment Type Full-Time
Minimum Experience Mid-level

Zentalis Pharmaceuticals is a San Diego based pharmaceutical company dedicated to the discovery and development of small molecule therapeutics targeting fundamental biological pathways of cancer. In the six years since our inception, we have successfully cleared four INDs with the FDA.  We believe our deep pipeline of oncology therapeutics has the potential to significantly improve the lives of patients with various types of cancer.


SUMMARY:

The Zentalis Structural Biology group is seeking an outstanding, detail-oriented, and motivated individual to join the scientific team. This individual will work both independently and collaboratively within the group as well as across multi-disciplinary drug discovery project teams. This position will be responsible for “gene to crystal” pursuits with particular emphasis on crystallization and small molecule co-crystallization of target proteins and protein complexes for X-ray crystallographic structure determination to enable structure-assisted optimization of lead compounds for oncology drug discovery programs.


RESPONSIBILITIES:

    • DNA expression construct design and generation for target protein expression; site-directed, insertional/deletional, and random mutagenesis/error-prone PCR
    • coli and insect cell recombinant protein expression leveraging different affinity tags and fusion proteins to enhance expression levels/solubility
    • Purification of protein from E. coli and insect cell hosts using FPLC systems by multiple affinity and separation techniques, affording mg quantities of crystallography-grade proteins for crystallization; proteolytic tag removal
    • Design, plan and execute crystallization trials using state-of-the-art commercially available sub-microliter crystallization instrumentation 
    • Crystallization of protein-small molecule complexes, identification of initial crystallization conditions and optimization, crystal soaking of small molecules, micro/macro seeding, crystal cryoprotection and harvesting in preparation for synchrotron data collection
    • Interpret crystal screening results, design and execute subsequent crystal optimization experiments from initial screening hits leading to well-ordered, diffraction-quality crystals affording high-resolution, quality structures
    • Peruse, read, and interpret primary literature involving structures of relevant and related oncology drug targets and apply this information to internal structure projects
    • Analyze, interpret and effectively report data at team meetings
    • Interface closely with structural biology colleagues to ensure robust purification schemes and crystal systems are established for targets in a timely fashion and aligned to the scientific project team goals
    • Work closely and collaboratively with structural biology colleagues to implement appropriate procedures, technologies, and instrumentation to establish and evolve a robust gene-to-structure workflow within the group
    • Maintain purification and crystallography instrumentation; ensure necessary crystallization reagents, supplies, equipment, and accessories are stocked
    • Other duties and projects as assigned

    QUALIFICATIONS:

    • BS with 5-8 years, or MS with 3-5 years’ experience in an X-ray crystallography lab setting, preferably with an emphasis on early drug discovery and structure-based drug design, with degree in biochemistry, molecular biology, biology, or related field
    • Scientific expertise in gene to crystal processes, with extensive experience and demonstrated technical proficiency, problem-solving, and understanding of core concepts pertaining to cloning, protein expression/purification, and crystallization
    • Maintain comprehensive, up to date records of experimental methods, results, and observations with high level of accuracy; effective oral and written communication skills;
    • Knowledge of oncology drug discovery is preferred
    • Ability to multi-task/ prioritize and effectively manage time of daily activities
    • Intermediate to advanced software skills (e.g., Microsoft Excel, PowerPoint, MS Project, DNA/Protein Analysis software)
    • Flexibility within a rapidly changing environment
    • Proficiency functioning in a goal and team-oriented setting
    • Well-developed organizational skills

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    • Location
      San Diego, California
    • Department
      Discovery Biology
    • Employment Type
      Full-Time
    • Minimum Experience
      Mid-level