Our lab uses host-pathogen interactions as a model for studying mechanisms of evolution.
Host-pathogen interfaces are battlefronts for influence over host functions. From an evolutionary perspective each interaction can bear heavily on the fitness of both hosts and pathogens. Therefore, these interactions drive some of the most rapid evolution found in nature and can provide basic insights into the evolutionary process.
We study the consequences of pathogen-driven evolution on cells and host immunity factors. Protein surfaces at these interfaces often evolve in a manner resembling molecular arms races. We are also interested in cases where pathogens use molecular mimicry to gain advantages against hosts. In addition, we use experimental evolution to determine the evolutionary potential of viruses and understand the rules by which they adapt.
Elde Lab Website (www.cellvolution.org)
Molecular Arms Races
Protein surfaces at host-pathogen interfaces often evolve in ways that resemble arms races. This phenomenon of genetic conflict has been described by the Red Queen hypothesis, which posits that antagonistic entities vie for dominance in seesawing battles of ongoing adaptations. Molecular arms races often play out repeatedly at the same interfaces and leave behind some of the strongest signals of natural selection in the genome. These arms races can be discerned using phylogenetic analysis, which can provide novel insights for studying the dynamics of host-pathogen interactions.
We are interested in cases where pathogens use mimicry to disrupt host processes. Mimicry is observed widely in nature (e.g. Batesian mimicry among butterfly species). However, little is known about how molecular mimicry impacts host-pathogen interactions. Pathogens use the strategy of mimicry to interfere with immunity and co-opt a wide variety of host processes to their advantage. This poses a conundrum for hosts to maintain critical activities while not being exploited by pathogenic mimics honed to divert host functions. What then are the evolutionary prospects for hosts to counteract mimics?
While experiments based on phylogenetic reconstructions, provide a powerful means of retrospectively studying host-pathogen interactions, experimental evolution offers a prospective view of virus evolution where potential adaptations can be monitored in real-time. Recent advances in deep sequencing coupled with recombinant tools make it possible to quickly determine the genetic basis of a variety of adaptations. We are using experimental evolution to address open questions related to virus evolution, such as mechanisms of rapid evolution and the trade-offs between host range and virulence.
Elde N.C., Roach, K., Yao M.C., Malik H.S. (2011) Absence of positive selection on centromeric histones in Tetrahymena suggests unsuppressed centromere-drive in lineages lacking male meiosis. Journal of Molecular Evolution, 72: 510-520.
Elde N.C., Malik H.S. (2009) The evolutionary conundrum of pathogen mimicry. Nature Reviews Microbiology, 7: 787-797.
Elde N.C., Child S.J., Geballe A.P., Malik H.S. (2009) Protein kinase R reveals an evolutionary model for defeating viral mimicry. Nature, 457: 485-489.
Rahaman A., Elde N.C., Turkewitz A.P. (2008) A dynamin-related protein required for nuclear remodeling in Tetrahymena. Current Biology, 18: 1227-1233.
Elde N.C., Long M., Turkewitz A.P. (2007) A role for convergent evolution in the secretory life of cells. Trends in Cell Biology, 17: 157-164.
Eisen J.A., Wu M., Wu D., Thiagarajan M., Wortman J.R., Badger J.H., Ren Q., Delcher A.L., Salzberg S.L., Silva J.C., Haas B.J., Majoros W.H., Farzad M., Carlton J.M., Garg J., Pearlman R.E., Karrer K.M., Sun L., Smith R.K., Elde N.C., Turkewitz A.P., Asai D.J., Wilkes D.E., Wang Y., Cai H., Collins K., Wilamowska K., Ruzzo W.L., Weinberg Z., Stewart B.W., Lee S.R., Wloga D., Rogowski K., Frankel J., Gaertig J., Gorovsky M.A., Cherry J.M., Stover N.A., Krieger C.J., Hamilton E.P., Orias E., Coyne R.S. (2006) Macronuclear genome sequence of the ciliate Tetrahymena thermophila, a model eukaryote. PLoS Biology, 4: e286.
Elde N.C., Morgan G., Winey M., Sperling L., Turkewitz A.P. (2005) Elucidation of clathrin-mediated endocytosis in Tetrahymena reveals an evolutionarily convergent recruitment of dynamin. PLoS Genetics, 1: e52.
Bowman G.R., Elde N.C., Morgan G., Winey M., Turkewitz A.P. (2005) Core formation and the acquisition of fusion competence are linked during secretory granule maturation in Tetrahymena. Traffic, 6: 303-323.
Doherty K.R., Zweifel E.W., Elde N.C., McKone M.J., Zweifel S.G. (2003) Random amplified polymorphic DNA markers reveal genetic variation in the symbiotic fungus of leaf-cutting ants. Mycologia, 95: 19-23.
Chilcoat N.D., Elde N.C., Turkewitz A.P. (2001) An antisense approach to phenotype-based gene cloning in Tetrahymena. Proc Natl Acad Sci U S A., 98: 8709-13.
|Nels Elde, Ph.D.
Senior Research Specialist
Department of Human Genetics
University of Utah
15 N 2030 E RM 6200
Salt Lake City, Utah 84112-5330
801-587-9026 - lab