Scientist/Lead Researcher Crystallography

The Fischer lab at St. Jude is recruiting a Scientist for a project that exploits the protein conformational landscape for ligand discovery in pediatric cancer. We are looking for applicants with a strong training in the gene-to-structure pipeline, including molecular biology, protein biochemistry, and structural biology (especially crystallography) and a keen interest or ideally experience in ligand discovery.

You will be part of an interdisciplinary team that uses modern structural biology (variable temperature crystallography) to characterize disease-relevant protein states, computational methods (MD, docking, custom software) to analyze and exploit them, and experiments (biophysical, biochemical, cell-based assays) to test the impact of small molecules on biology and disease. These approaches are also relevant for allosteric regulation of proteins and protein-protein interactions.

The successful candidate will have these attributes:

1) Must be able to conduct independent research in molecular biology and protein biochemistry, including cloning and protein purification, that enable structural studies.

2) Demonstrated experience in protein crystallography (from crystallization to data collection to refinement, analysis and deposition)

3) Familiarity with large-scale/ high-throughput approaches, automation, liquid handling, biophysical/ biochemical assays or computational approaches is desirable.

4) Experience with expression systems other than E. coli is a plus such as insect cells.

5) Proficiency in e.g. python or shell scripting will facilitate scaling up data analysis.

6) Must be eager to learn and implement new techniques from relevant areas.

Besides working on your own projects, you will form a liaison for other lab members and support projects within the lab while maintaining efficient laboratory operations.

Our group is housed in the Department of Chemical Biology and Therapeutics, and Structural Biology at St. Jude Children's Research Hospital. With ongoing investments into exceptional structural and chemical biology facilities, this is an exciting time to join our lab to do cutting-edge research whilst living in an affordable city. Stable funding for this post is available.

Relevant papers include:

• Bradford et al. (2021). Temperature artifacts in protein structures bias ligand-binding predictions. Chemical Science 12, 11275-11293.

• Fischer (2021). Macromolecular room temperature crystallography. Q Rev Biophys 54, E1.

• Darby et al. (2019). Water Networks Can Determine the Affinity of Ligand Binding to Proteins. JACS 141, 15818-26.

• Balius et al. (2017). Testing inhomogeneous solvation theory in structure-based ligand discovery. PNAS E6839-46.

• Fischer et al. (2015). One crystal, two temperatures: cryocooling penalties alter ligand binding to transient protein sites. Chembiochem 16, 1560-64.

• Fischer et al. (2014). Incorporation of protein flexibility & conformational energy penalties in docking screens to improve ligand discovery. Nature Chemistry 6, 575-83.

Minimum Education

• Bachelors degree in relevant scientific area is required.

Minimum Experience

Scientist

• Seven (7) years of relevant post-degree work experience is required.

• Five (5) years of relevant post-degree work experience is required with a Masters degree.

• Three (3) years of relevant post-degree work experience is required with a PhD.

Lead Researcher

• Five (5) years of relevant, post-degree work experience is required with a Bachelors degree.

• Two (2) years of relevant post-degree work experience is required with a Masters degree.

• No experience is required with a PhD degree.