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Assembly of Bacterial Outer Membrane Proteins

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD and surrounding area

Position Description:

A postdoctoral position is available in the laboratory of Dr. Harris Bernstein (Genetics and Biochemistry Branch/NIDDK) to investigate the assembly (folding and membrane integration) of outer membrane proteins (OMPs) in Gram-negative bacteria using a combination of biochemical, biophysical, and structural approaches. While most proteins that integrate into biological membranes contain α-helical membrane spanning segments, OMPs contain a folded “β barrel” structure that serves as a membrane anchor. Although an essential heterooligomer called the barrel assembly machinery (Bam) complex has been shown to catalyze the membrane insertion of OMPs, its mechanism of action is unknown. Our goal is to elucidate the function of the Bam complex in E. coli by examining the assembly of a variety of different model OMPs ranging from simple proteins that consist entirely of a β barrel to more complex proteins such as “autotransporters”, a family of virulence factors produced by pathogenic bacteria, that contain a large extracellular domain in addition to a β barrel. Because compounds that exhibit strong antimicrobial activity have recently been described that inhibit the Bam complex, our work may lead to strategies to develop new antibiotics.

For examples of our recent work, please see Doyle MT, et al. (2022) Cell 185: 1143-1156; Doyle MT and Bernstein, HD (2021) Mol Cell 81: 2000-2012; Wang X et al. (2021) mBio 12: e00597; Doyle MT and Bernstein HD (2019) Nat Commun 10: 3358; Sikdar R, et al. (2017) Nat Commun 8:1309. Further information about our research can also be found at https://www.niddk.nih.gov/about-niddk/staff-directory/biography/bernstein-harris.

Qualifications:

Candidates should have a Ph.D. and/or M.D. degree (or anticipate receiving their degree before the start of their fellowship) and experience in microbiology, biochemistry, biophysics, structural biology or a related field.

To Apply:

Interested individuals should email their CV, a cover letter summarizing current and future research interests, and contact information for three references to Dr. Harris Bernstein at harris_bernstein@nih.gov.

Posted Until: 9/3/2022

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