Structural biology of host-pathogen interactions

Thilo Stehle

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  • Ph.D. in Chemistry 1992, University of Freiburg
  • Postdoctoral training 1992-1997, Harvard University
  • Assistant Professor 1997-2004, Harvard Medical School
  • Professor of Biochemistry since 2005

Research Interest

The long-range goal of our research is to advance an understanding of the interactions between pathogens and hosts, in order to describe mechanisms of pathogen engagement of target cells and to provide a basis for vaccine and drug design. We study viruses as well as bacterial pathogens. We use protein crystallography, in combination with other structural approaches and associated biochemical techniques, to establish the three-dimensional structures and function of bacterial and viral proteins, often in complex with cognate ligands such as cellular receptors or substrates.

A particular emphasis is placed on understanding basic principles of protein-protein and protein-carbohydrate interactions. Many such interactions are well characterized at a functional level, yet poorly understood at the molecular or atomic level. However, such knowledge is needed to develop compounds that are able to modulate or block biological interactions. For example, by studying the determinants of viral attachment to host cells and establishing principles of attachment, one can develop molecules that interfere with binding. It also becomes possible to redirect or retarget viruses to different receptors, which is highly relevant for gene delivery approaches.

  • TStehle new figure 16
    click to enlarge

Left: Structure of entire polyomavirus particle bound to glycan receptor.

Right: Detailed view of interactions in one binding site (see Neu et al., Cell Host Microbe 2010 for details).

Available PhD Projects

We have projects available that focus on virus-receptor interactions of adenoviruses and polyomaviruses. In both cases, we are particularly interested in advancing knowledge about the parameters that guide attachment to glycan-based receptors, with the ultimate goal of modulating and/or interfering with these interactions.

Selected Reading

1) Stencel-Baerenwald JE, Reiss K, Reiter DM, Stehle T, Dermody TS. The sweet spot: defining virus-sialic acid interactions. Nat Rev Microbiol 2014; 12:739-49.

2) Ströh LS, Stehle T. Glycan engagement by viruses: receptor switches and specificity. Annu Rev Virol 2014; 1:285-306.

3) Stehle T, Khan ZM. Rules and exceptions: sialic acid variants and their role in determining viral tropism. J Virol. 2014; 88:7696-9.