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Laurie Elizabeth Comstock
Associate Microbiologist, Brigham and Women's Hospital
Associate Professor of Medicine, Harvard Medical School

Brigham and Women's Hospital
Department of Medicine
Infectious Diseases
75 Francis Street
Boston, MA 02115

Research Narrative:

The human intestinal microbiota is one of the densest microbial ecosystems on earth containing approximately 1012 organisms per gram of colonic contents and comprised of hundreds of different species.  In recent years, the topic of the intestinal microbiota has gained much interest by the scientific community and the NIH has made a tremendous investment in studying the human microbiome.  Despite the heightened interest in the intestinal microbiota, investigations into the dynamic microbial interactions that occur within this ecosystem are still in their infancy.  Little is known about how bacterial species become established in the mammalian intestine, the interactions that occur between competing species, and the factors that influence microbial stability and diversity in the ecosystem. 

My laboratory studies the basic biology of a predominate order of bacteria of the human intestine, the Bacteroidales.  These are the most abundant Gram negative bacteria of this ecosystem and establish mutualistic relationships with their hosts in that they both receive and provide beneficial properties.  We study various aspects of these bacteria that allow them to survive and thrive in the human gut.  We are also very interested in population and community dynamics of the intestinal microbiota, community stability, and how these bacteria interact with other members of the intestinal microbiota.  These studies are an essential prerequisite to understanding how they provide beneficial properties to humans and how the composition of the microbiota may be manipulated for human health.

There are numerous translational aspects to these studies.  By understanding the factors that contribute to compositional changes in this ecosystem, and how we can shape the composition of the microbiota, we will eventually be able to use these data to manipulate the bacterial community for better health outcomes.  Designer “symbionts/probionts” could be used to deliver immunogenic molecules for vaccines, antimicrobial molecules targeting harmful bacteria such as Clostridium difficile, and for the delivery of other health promoting molecules.

Bowman Gray School of Medicine, Wake forest University, 1991, Ph.D.

Publications (Pulled from Harvard Catalyst Profiles):

1. Comstock LE. Small RNAs Repress Expression of Polysaccharide Utilization Loci of Gut Bacteroides Species. J Bacteriol. 2016 Sep 15; 198(18):2396-8.

2. Roelofs KG, Coyne MJ, Gentyala RR, Chatzidaki-Livanis M, Comstock LE. Bacteroidales Secreted Antimicrobial Proteins Target Surface Molecules Necessary for Gut Colonization and Mediate Competition In Vivo. MBio. 2016 Aug 23; 7(4).

3. Rakoff-Nahoum S, Foster KR, Comstock LE. The evolution of cooperation within the gut microbiota. Nature. 2016 05 12; 533(7602):255-9.

4. Coyne MJ, Comstock LE. A New Pillar in Pilus Assembly. Cell. 2016 Apr 21; 165(3):520-1.

5. Chatzidaki-Livanis M, Geva-Zatorsky N, Comstock LE. Bacteroides fragilis type VI secretion systems use novel effector and immunity proteins to antagonize human gut Bacteroidales species. Proc Natl Acad Sci U S A. 2016 Mar 29; 113(13):3627-32.

6. Coyne MJ, Roelofs KG, Comstock LE. Type VI secretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements. BMC Genomics. 2016 Jan 15; 17:58.

7. Liu S, da Cunha AP, Rezende RM, Cialic R, Wei Z, Bry L, Comstock LE, Gandhi R, Weiner HL. The Host Shapes the Gut Microbiota via Fecal MicroRNA. Cell Host Microbe. 2016 Jan 13; 19(1):32-43.

8. Chatzidaki-Livanis M, Comstock LE. Friend turned foe: a role for bacterial sulfatases in colitis. Cell Host Microbe. 2015 May 13; 17(5):540-1.

9. Chatzidaki-Livanis M, Coyne MJ, Comstock LE. An antimicrobial protein of the gut symbiont Bacteroides fragilis with a MACPF domain of host immune proteins. Mol Microbiol. 2014 Dec; 94(6):1361-74.

10. Rakoff-Nahoum S, Comstock LE. Immunology: Starve a fever, feed the microbiota. Nature. 2014 Oct 30; 514(7524):576-7.