The goals of this proposal are to improve our understanding of both the evolution and management of influenza by developing a unified modeling framework. In particular, the questions we will address are (1) How do given strain and subtype structures, and the associated patterns of cross-reactivity, affect disease dynamics? (2) How does cross-reactivity affect pathogen evolution? (3) How do strain structure and patterns of cross-reactivity self-organize over evolutionary time, for example into quasi-species, and how does this organization feed back to affect dynamics? (4) What are the implications of these issues for vaccination strategies, and what are the reciprocal effects of vaccination programs upon the organization of the viral population?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM060729-02
Application #
6343112
Study Section
Special Emphasis Panel (ZRG1-GEN (01))
Program Officer
Eckstrand, Irene A
Project Start
2000-01-01
Project End
2003-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
2
Fiscal Year
2001
Total Cost
$192,803
Indirect Cost
Name
Princeton University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Forsberg, Roald; Drummond, Alexei J; Hein, Jotun (2005) Tree measures and the number of segregating sites in time-structured population samples. BMC Genet 6:35
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Pedersen, Jakob Skou; Forsberg, Roald; Meyer, Irmtraud Margret et al. (2004) An evolutionary model for protein-coding regions with conserved RNA structure. Mol Biol Evol 21:1913-22
Einer-Jensen, Katja; Ahrens, Peter; Forsberg, Roald et al. (2004) Evolution of the fish rhabdovirus viral haemorrhagic septicaemia virus. J Gen Virol 85:1167-79
Pedersen, Jakob Skou; Meyer, Irmtraud Margret; Forsberg, Roald et al. (2004) A comparative method for finding and folding RNA secondary structures within protein-coding regions. Nucleic Acids Res 32:4925-36
Forsberg, Roald; Christiansen, Freddy Bugge (2003) A codon-based model of host-specific selection in parasites, with an application to the influenza A virus. Mol Biol Evol 20:1252-9
Plotkin, Joshua B; Dushoff, Jonathan (2003) Codon bias and frequency-dependent selection on the hemagglutinin epitopes of influenza A virus. Proc Natl Acad Sci U S A 100:7152-7
Rodrigo, Allen G; Goode, Matthew; Forsberg, Roald et al. (2003) Inferring evolutionary rates using serially sampled sequences from several populations. Mol Biol Evol 20:2010-8

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