John Doe

Research

"It takes all the running you can do, to keep in the same place."
- The Red Queen to Alice, in Lewis Carroll’s Through the Looking Glass

Pathogens and their hosts are locked in a constant struggle for evolutionary dominance. Any host adaptation that leads to more effective defense against a pathogen will almost inevitably drive adaptation in the pathogen to escape such defenses. Thus, the only way either side can survive is to continually adapt, as proposed in Leigh Van Valen’s ‘Red Queen hypothesis’. These escalating arms races play out at the level of rapid evolution of host-pathogen interactions, constantly selecting for molecular innovations that either protect the host or evade host defenses. However, the molecular details of these rapidly evolving host-pathogen interactions, and the consequences of these conflicts on human susceptibility to current and emerging infectious diseases, are mostly unexplored.

Our research aims to use these evolutionary principles, combined with virology and mechanistic biochemistry, to understand how our immune system has evolved to defend against pathogens and how pathogens counter-evolve to defeat host immunity. One of the approaches we take is to use comparative genomics to identify characteristic signatures of pathogen-driven innovation (e.g. rapid sequence evolution, horizontal gene transfer, gene birth and death, and gene recombination). Interestingly, we expect these rapidly evolving genes to be at the center of host-pathogen conflicts, yet many of them are almost entirely uncharacterized. This provides an opportunity to use pathogens to discover novel biological functions that are involved in not only pathogen immunity but also more global cellular regulation. Current projects in the lab focus on functional characterization of two such poorly understood systems: post-transcriptional modification of RNA to molecularly distinguish between different RNAs (e.g. host RNA versus viral RNA), and post-translational modifications of proteins to regulate their function. The ultimate goal of our research is to understand the rapidly evolving molecular means by which hosts and pathogens battle each other, while at the same time providing insight into how genetic variation resulting from these conflicts contributes to differences in human susceptibility to infectious diseases.

Publications

  • Moens, U., Calvignac-Spencer, S., Lauber, C., Ramqvist, T., Feltkamp, M.C.W., Daugherty, M.D., Verschoor, E.J. and B. Ehlers (2017). ICTV Virus Taxonomy Profile: Polyomaviridae. J General Virology. 98, 1159-60.
  • Chavarria-Smith, J., Mitchell, P.S., Ho, A.M., Daugherty, M.D.* and R.E. Vance*. (* co-corresponding authors) (2016). Functional and Evolutionary Analyses Identify Proteolysis as a General Mechanism for NLRP1 Inflammasome Activation. PLoS Pathogens. 12, e1006052.
  • Daugherty, M.D., Schaller, A.M., Geballe, A.P, and H.S. Malik. (2016). Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals. eLife. 5, e14228.
  • Chou, S.*, Daugherty, M.D.*, Peterson, S.B., Biboy, J., Yang, Y., Jutras, B.L., Fritz-Laylin, L.K., Ferrin, M.A., Harding, B.N., Jacobs-Wagner, C., Yang, X.F., Vollmer, W., Malik, H.S. and J.D. Mougous. (*these authors contributed equally) 2015. Transferred interbacterial antagonism genes augment eukaryotic innate immune function. Nature. 518, 98-101.
  • Daugherty, M.D., Young, J.M., Kerns, J.A., and H.S. Malik. 2014. Rapid evolution of PARP genes suggests a broad role for ADP-ribosylation in host-virus conflicts. PLoS Genetics. 10, e1004403.
  • Carter, J.J.*, Daugherty, M.D.*, Qi, X., Bheda-Malge, A., Wipf, G.C., Robinson, K., Roman, A., Malik, H.S. and D.A. Galloway. (*these authors contributed equally) 2013. Identification of an overprinting gene in Merkel cell polyomavirus provides evolutionary insight into the birth of viral genes. Proceedings of the National Academy of Sciences. 110, 12744-9.
  • Daugherty, M.D. and H.S. Malik. 2012. Rules of engagement: molecular insights from host-virus arms races. Annual Review of Genetics. 46, 677-700.
  • Daugherty, M.D., Liu, B, and A.D. Frankel. 2010. Structural basis for cooperative RNA binding and export complex assembly by HIV Rev. Nature Structural and Molecular Biology. 17, 1337-42.
  • Daugherty, M.D., D’Orso, I., and A.D. Frankel. 2008. A solution to limited genomic capacity: Using adaptable binding surfaces to assemble the functional HIV Rev oligomer on RNA. Molecular Cell. 31, 824-834.