Home Faculty and Research Faculty by Name Greg Barton

Greg Barton

Assistant Professor of Immunology and Pathogenesis

Lab Homepage: http://mcb.berkeley.edu/labs/barton/

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Research Interests

My lab studies the innate immune system. We are particularly interested in the Toll-like receptor (TLR) family. Work in the lab is currently focused on understanding how TLRs mediate differential responses to distinct pathogen classes. These studies have implications for the study of infectious disease, autoimmunity, and vaccine development.

TLRs are essential sensors of microbial infection that detect and respond to a broad variety of invading pathogens, including viruses, bacteria, fungi, and protozoa. Unlike the antigen receptors of B and T cells whose specificities are generated randomly, the specificity of each TLR is predetermined. Consequently, TLRs have evolved to recognize highly conserved features of microbes, such as components of bacterial cell walls or nucleic acid genomes of viruses. By linking TLR activation to key signals required for initiation of the immune response, the immune system ensures that responses are limited to those aimed against foreign pathogens and not self-tissues. Accordingly, the signals induced by TLRs are critical for the immune response at both the innate and adaptive levels.

Each TLR has evolved due to unique selective pressures which have shaped how that TLR functions. The key characteristics that distinguish individual TLRs are ligand specificity, signal transduction pathways, expression profiles and sub-cellular localization. Evolution has linked recognition of a certain pathogen with expression in certain cell types and with the induction of certain genes. The logic behind the particular combinations of these features for each TLR is unknown and represents one of the most fundamental aspects of TLR biology. Our goal is to use in vivo models to reveal the principles that govern how this receptor system works.

Current Projects

We are currently focusing on 3 areas:

1) TLR cellular localization. The cell biology of TLRs has not been well defined, yet it is increasingly clear that differential localization within the cell is one way in which TLR function is regulated. We have generated TLR mutants with altered localization and are currently examining the effect of this re-localization in vivo.

2) TLR signaling specificity. TLRs induce overlapping yet distinct sets of genes based on differences in the downstream signaling pathways that they activate. The relevance of these differences in signaling for the immune response to different types of pathogens remains unclear. We have generated mice expressing chimeric TLRs with redirected signal transduction to address this question.

3) TLR expression. TLR expression varies considerably among different cell types. Importantly, these different cell types play distinct roles during the immune responses to different types of pathogens. We are using in vivo models based on altered TLR expression to address how differential TLR expression contributes to the specificity of the immune response during infection.

Selected Publications

Horng T, Barton GM, Medzhitov R. 2001. TIRAP: an adapter molecule in the Toll signaling pathway. Nat Immunol. 2: 835-41.

Schnare M, Barton GM, Holt AC, Takeda K, Akira S, Medzhitov R. 2001. Toll-like receptors control activation of adaptive immune responses. Nat Immunol. 2: 947-50.

Barton GM, Medzhitov R. 2002. Control of adaptive immune responses by Toll-like receptors. Curr Opin Immunol. 14: 380-3.

Barton GM, Medzhitov R. 2002. Retroviral delivery of small interfering RNA into primary cells. Proc Natl Acad Sci USA. 99: 14943-5.

Horng T, Barton GM, Flavell RA, Medzhitov R. 2002. The adaptor molecule TIRAP provides signaling specificity for Toll-like receptors. Nature. 420: 329-33.

Barton GM, Medzhitov R. 2003. Linking Toll-like receptors to IFN-alpha/beta expression. Nat Immunol. 4: 432-3.

Barton GM, Medzhitov R. 2003. Toll-like receptor signaling pathways. Science. 300: 1524-5.

Barton GM, Kagan JC, Medzhitov R.  2006. Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA.  Nat Immunol. 7: 49-56.

Barton GM.  2007.  Viral recognition by Toll-like receptors.  Semin Immunol.  19: 33-40.

Last Updated 2007-11-07