BBS Faculty Member - Marcia Goldberg

Marcia Goldberg

Department of Microbiology and Immunobiology

University Park
Bacterial Pathogenesis Laboratories
65 Landsdowne Street, Room 423
Cambridge, MA 02139
Tel: 617-768-8740; Lab: 617-768-8741
Fax: 617-768-8738
Email: mgoldberg1@partners.org
Lab Members: 3 postdoctoral fellows, 2 graduate students, 2 undergraduates
Visit my lab page here.



Our lab focuses on the molecular nature of interactions between microbial pathogens and the host. Pathogenic bacteria have evolved complex mechanisms to subvert host cell signaling pathways to enhance disease processes. Our work focuses on uncovering the molecular signaling events that occur during bacterial infection of host cells. The bacterial pathogen Shigella, a major cause of illness and mortality among children worldwide, infects cells of the intestinal epithelium and uses cellular actin cytoskeletal and other pathways to disseminate through host tissue. We are investigating the molecular mechanisms by which secreted bacterial proteins modulate host proteins to divert the host signaling pathways involved in these processes. Our approaches include both genome-wide screening and targeted investigations.

Inside the host cell cytoplasm, Shigella polymerizes host cell actin into a propulsive tail at one end of the bacterial body. Assembly of this tail generates the force to propel the bacterium to the cell periphery. A remarkable characteristic of the Shigella actin assembly protein (IcsA) is its localization to the old pole of the bacterium. Precise spatial positioning of proteins is key to many cellular functions in prokaryotes; however, as yet, the basic mechanisms that mediate this positioning remain largely unknown. We have shown that the mechanism by which IcsA is positioned in the cell is representative of a general mechanism of protein positioning that is fundamental to bacterial cell biology and is present in a wide range of bacterial organisms. A second major focus of our research is to characterize the molecular mechanisms of spatial positioning of proteins in bacteria.



Last Update: 8/22/2013



Publications

For a complete listing of publications click here.

 

 

Fixen KR, Janakiraman A, Garrity S, Slade DJ, Gray AN, Karahan N, Hochschild A, Goldberg MB. A genetic reporter system for positioning of proteins at the bacterial pole. mBio. 2012. 3(2): pii: e00251-11 doi: 10.1128/mBio.00238-11.

Gray AN, Henderson-Frost JM, Boyd D, Shirafi S, Niki H, Goldberg MB. Unbalanced charge distribution as a determinant for dependence of a subset of E. coli membrane proteins on the membrane insertase YidC. mBio. 2011. 2(6): pii: e00238-11 doi:10.1128/mBio.00238-11. (Faculty of 1000 Biology)

Heindl JE, Saran I, Yi C-R, Lesser CF, Goldberg MB. Requirement for formin-induced actin polymerization during spread of Shigella. Infect Immun. 2010. 178:193-203.

Leung Y, Ally S, Goldberg MB. Bacterial actin assembly requires Toca-1 to relieve N-WASP autoinhibition. Cell Host Microbe. 2008; 3:39-47.



© 2013 by the President and Fellows of Harvard College