Institute Research Investigator Structural Biology

MD ANDERSON THERAPEUTICS DISCOVERY DIVISION

Within The University of Texas MD Anderson Cancer Center lies a powerful engine driving the future of new targeted, immune- and cell-based therapies: the Therapeutics Discovery Division. Therapeutics Discovery eliminates the bottlenecks that hamper traditional drug discovery, with a multidisciplinary team of dedicated researchers, doctors, drug developers and scientific experts working together to develop small-molecule drugs, biologics and cellular therapies. Our unique structure and collaborative approach allow the team to work with agility, bringing novel medicines from concept to clinic quickly and efficiently - all under the same roof.

The Therapeutics Discovery Division is built around four platforms: The Institute for Applied Cancer Science (IACS), ORBIT (Oncology Research for Biologics and Immunotherapy Translation), TRACTION (Translational Research to Advance Therapeutics and Innovation in Oncology) and the Neurodegeneration Consortium.

The IACS platform is focused on discovering and developing the next generation of small-molecule targeted therapies, driven by the needs we see in our patients. The team aligns world-class drug discovery and development research with the science and clinical care for which MD Anderson is known. We work in a fast-paced, milestone-driven environment with a focus on team science and interdisciplinary research. Our unique approach has created a biotech-like engine within the walls of the nation's leading cancer center to bring life-saving medicines to our patients more quickly and effectively. This model already has achieved results, with multiple programs currently in clinical and late-stage preclinical development.

The Institute Research Investigator in the structural chemistry group of the Institute for Applied Cancer Science (IACS) participates in cross-functional research to advance our drug discovery projects from early exploratory efforts through lead optimization, ultimately delivering therapeutic agents of benefit to patients. As part of the IACS team, the Institute Research Investigator will be responsible for solving single-particle cryo-EM structures of target proteins and complexes, supporting the design of novel therapeutics by elucidating small molecule binding modes, and identifying opportunities for allosteric or molecular glue-based protein modulation.

By joining the Therapeutics Discovery Division, you have the opportunity to use your talents to make a direct impact on the lives of our patients. We are seeking a highly motivated and collaborative individual to become a part of our team. The ideal candidate will have a demonstrated track record of solving challenging protein structures using single-particle cryo-electron microscopy and X-ray crystallography.

Key Functions

1. Apply and develop cutting edge single-particle cryo-EM tools and methodologies to enable advancement of Institute projects through leadership and experimental activities. Analyze structural data generated by various studies and leverage results for the design of future studies.
2. Work in close collaboration with cross-functional drug discovery project teams by leveraging the latest structural biology and structural bioinformatics approaches.
3. Generate high-resolution structures of key small molecule compounds bound to their protein targets using cryo-EM and/or X-ray crystallography.
4. Solve structures of target proteins within biologically relevant complexes to identify opportunities for allosteric inhibition and/or modulation by molecular glues.
5. Collaborate with medicinal and computational chemists in the design of compounds with improved affinity, selectivity, and properties using protein structural information.
6. Design novel protein constructs to enable pull-down of biologically relevant complexes and improve protein expression, purification, crystallization, and aggregation.
7. Optimize cryo-EM grid conditions to improve data quality and consistency.
8. Carry out biophysical experiments to evaluate protein-ligand binding affinity and prioritize ligands for structural work.
9. Communicate structural biology results to a broad scientific audience from diverse disciplines.
10. Employ safe lab practices.
11. Maintain research records and laboratory notes.

EDUCATION:
Required: Bachelor's degree in biology, biochemistry, molecular biology, cell biology, enzymology, pharmacology, chemistry or related field.

Preferred: PhD in one of the natural sciences or related field or Medical degree.

EXPERIENCE:

Required: Six years experience of relevant research experience in laboratory. With a Master's degree, four years of required experience. With a PhD in a natural science or Medical degree, no experience required.

Preferred: Extensive knowledge of contemporary single-particle cryo-EM, and familiarity with X-ray crystallography, nuclear magnetic resonance, and/or structural bioinformatics, as evidenced by a strong publication record in peer reviewed journals. Extensive experience with cryo-EM sample preparation (eg. vitrobot, Leica) and data collection on modern microscopes (eg. Glacios, Krios, Tundra). Expert knowledge of the latest single-particle cryo-EM data processing software (eg. CryoSPARC, RELION, etc.) and familiarity with crystallographic refinement software. Experience using biophysical methods (eg. ITC, SPR, DSF, MST) to evaluate protein-ligand binding affinity, binding kinetics, complex formation, etc. Experience solving structures of membrane proteins. Excellent communication, writing, and organizational skills. Experience working with medicinal and computational chemists.

It is the policy of The University of Texas MD Anderson Cancer Center to provide equal employment opportunity without regard to race, color, religion, age, national origin, sex, gender, sexual orientation, gender identity/expression, disability, protected veteran status, genetic information, or any other basis protected by institutional policy or by federal, state or local laws unless such distinction is required by law. http://www.mdanderson.org/about-us/legal-and-policy/legal-statements/eeo-affirmative-action.html