U.S. Department of Health and Human Services
Harris Bernstein

 Contact Info

Tel: 301-402-4770
Email: harris_bernstein@nih.gov

 Select Experience

  • Ph.D.Massachusetts Institute of Technology1987
  • B.A.Harvard University1980

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Harris D. Bernstein, Ph.D.

Section Chief, Protein Biogenesis SectionGenetics and Biochemistry Branch
  • Microbiology/Infectious diseases (non-viral)
  • Molecular Biology/Biochemistry
Research Summary/In Plain Language

Research in Plain Language

Living cells can be thought of as extremely sophisticated machines that only function if all of the parts are in the right place. Imagine a car in which the steering wheel is in the trunk and the wheels are on the roof. Such a vehicle wouldn’t be very useful!

Most biochemical reactions are performed by proteins, which are manufactured inside living cells. In addition to folding into a defined three-dimensional shape, many proteins must be transported across one or more membrane barriers or embedded in a membrane in order to reach the location where they perform their jobs. We are currently studying protein localization in Gram-negative bacteria, a large group of unicellular organisms that are bounded by a double membrane. We are especially interested in understanding the process by which proteins that must be transported across the first or “inner” membrane and then inserted into the second or “outer” membrane are localized. In many of our experiments we have focused on the localization of a specific family of outer membrane proteins called autotransporters. These proteins are especially interesting because they contain two segments, one that is embedded in the outer membrane and one that is transported across the outer membrane into the extracellular space. The segment that is exposed on the cell surface enhances the ability of many “pathogenic” bacteria to cause disease. We have found that autotransporter localization is a complex, multistep process involving the participation of several molecular machines that are dedicated to preparing client proteins to insert into (or cross) the outer membrane and to helping them fold correctly. We hope that our work will lead to the development of new strategies to block the localization of autotransporters and other outer membrane proteins and thereby prevent or treat bacterial diseases.

In a separate project we are trying to understand how bacteria that are benign, naturally occurring inhabitants of the human colon transport proteins into the environment. We hope that the knowledge we gain will ultimately enable us to produce modified bacteria that export specific proteins into the colon to fight illnesses such as inflammatory bowel disease.