Elizabeth Campbell, Ph.D.

Senior Research Associate, Darst Lab
Laboratory of Molecular Biophysics


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Research Areas: Biochemistry, Biophysics, Chemical Biology, Microbiology and Structural Biology


Studies the structure and function Mycobacterium tuberculosis RNA polymerase as a target for antimicrobial therapy.


Tuberculosis (TB), caused by Mycobacterium tuberculosis, continues to pose a major health problem. RNA polymerase, the enzyme responsible for all transcription in bacteria, is a proven and effective target for antimicrobials, and is one of the primary targets for antimicrobial treatment of TB. We use a combination of approaches to study the mycobacterial transcription cycle to aid in the development of new antibiotics to treat TB.

 TB continues to pose a major health problem. The Center for Disease Control (CDC) estimates that one third of the world is infected, approximately 8 million people become sick and 1.8 million TB-related deaths occur annually. Efforts to treat TB have been greatly impeded due to the increase in MDR Mycobacterium tuberculosis (Mtb) strains, which is defined as by the World Health Organization (WHO) as being resistant to “at least, isoniazid and rifampicin, the two most powerful anti-TB medicines”. Approximately 4% of new cases (~580,000 in 2015) are rifampicin resistant (RifR) and 83% of those cases are MDR. Unfortunately, there is only a 52% success rate in treating MDR TB, therefore, to continue efforts to eradicate TB and to treat MDR, new antimicrobial therapies are essential. The bacterial RNAP is a clinically proven target with two classes of antibiotics (Rif being one of them) already in clinical use to treat pathogenic bacteria. Therefore, we study mycobacteria RNAP and the proteins that regulate the mycobacterial transcription cycle to provide structural and functional insights to guide drug discovery and optimization.

I lead a subgroup of the Darst Laboratory studying mycobacteria RNAP. Our group has shown that the enzyme exhibits kinetic properties different from the archetypical Escherichia coli, initiating transcription at much slower rates. We found that two transcription factors that are essential in mycobacteria but absent in E. coli, CarD and RbpA, are critical to boost the rate of DNA unwinding at promoters, and our structural and functional data explain their mechanisms of activation. We were the first group to solve the atomic resolution structure of a mycobacteria RNA polymerase and we exploit this breakthrough to solve structures of the enzyme with known antibiotics, derivatives of known antibiotic, and new antibiotics in collaboration with the group of Sean Brady and other investigators.


We are also using cryo-electron microscopy to determine structures of Mtb RNAP to near atomic resolution with various ligands (DNA, inhibitors, and apo).  These “solution” studies have allowed us to observe conformations of the RNA polymerase never before observed in the absence of crystal-packing.  We are currently using a combination of X-ray crystallography, Cryo-EM and biochemistry to 1) elucidate how the enzyme’s conformations observed in the cryo-EM structures correlate with the kinetic steps of mycobacteria transcription initiation and 2) as a platform for revealing the mechanisms and molecular interaction between RNA polymerase and inhibitors with the goal to facilitate the development of new antimicrobial treatments against TB.




B.A. in Biology, 1992

Swarthmore College


Ph.D. in Microbial Pathogenesis, 1998

The Rockefeller University



The Rockefeller University, 1998-2003



Research Associate, 2003-2011

Senior Research Associate, 2003

The Rockefeller University



Fellowship in the American Academy of Microbiology

John Kluge Graduate Fellow, The Rockefeller University

NSF Minority Graduate Fellow, National Science Foundation

American Society for Microbiology Student Travel Grantee, American Society for Microbology

Segal Travel Grantee, The Rockefeller University

The Rockefeller Postdoctoral Fellowship award

Individual National Research Service award, National Institutes of Health





Boyaci H, Chen J, Lilic M, Palka M, Mooney RA, Landick R, Darst SA*, Campbell EA* Fidaxomicin Jams Myocbacterium tuberculosis RNA polymerase motions needed for initiation via RbpA contacts. eLife (2018);7:e34823. Doi:10.7554/eLIfe.34823

Hubin EA, Lilic M, Darst SA and E.A. Campbell*. Structural insights into the mycobacteria transcription initiation complex from analysis of X-ray crystal structures. Nature Communications. (2017); 8:16072.

Hubin, E.A., Fay. A., Xu, C., Bean, J., Saecker, R.M., Glickman, M., Darst, S.A.* and E.A. Campbell*. Structure and function of the mycobacterial transcription initiation complex with the essential regulator RbpA. (2017) Elife6, e22520.

Hubin EA, Tabib-Salazar A, Humphrey LJ, Flack JE, Olinares PD, Darst SA, Campbell EA*, Paget MS*. Structural, functional, and genetic analyses of the actinobacterial transcription factor RbpA. Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7171-6.Bae, B. et al.

Bae, B., Chen, J., Davis, E., Leon, K., Darst S.A. & E.A. Campbell* CarD uses a minor groove wedge mechanism to stabilize the RNA polymerase open promoter complex. (2015) Elife 4, e08505.