Abstract

Theevolutionofproteinsunderpinsawiderangeoffundamentallyimportantbiological processes,includingtheadaptationofvirusesthatarerelevanttohumanhealth.Overthelast fewdecades,acombinationofexperimentalandobservationalapproacheshasprovidedagreat dealofqualitativeunderstandingintoproteinevolution.Thegoaloftheproposedresearchisto usethisunderstandingtoguidetheconstructionofquantitativemodelsofproteinevolutionthat areinformedbyexperiments.Suchmodelsareessentialtoleverageburgeoningnewsourcesof experimentaldataonproteinandvirusevolution.Theproposedresearchcentersonfour interconnectedgoals:(1)Quantifytheextentthatexperimentalmeasurementsoftheeffectsof singleanddoublemutationscanbegeneralizedtoanevolutionarilyrelevantspanofprotein homologsorviralstrains.(2)Developstatisticaltechniquestoassesstheadequacyof experimentsfordescribingactualnaturalselection,includingwhentheseexperimentsmeasure epistaticinteractions.(3)Devisehigh-??throughputexperimentstoidentifymutationsthatenable influenzavirustoadapttonewhosts,andusetheresultingmeasurementstoscorethe pandemicriskposedbyviralstrains.(4)Relatetheevolutionofinfluenzaviruswithinsingle infectedhumanstotheconstraintsandselectiononthevirus?slong-??termevolutionataglobal scale.Allfourofthesegoalsleveragenewtypesofdatatoinformbetteranalysesofevolutionin nature.Theresultinginsightsandmethodswilladvancebasicevolutionarybiology,andwillbe directlyrelevanttothestudyofbiomedicallyimportantvirusessuchasinfluenza.

Public Health Relevance

Wewillleveragenewsourcesofdatatodevelopquantitativemodelsoftheevolutionof proteinsandviruses.Thisworkwillprovidefundamentalinsightintotheevolutionary processesthatunderliepublic-??healthrelevanteventssuchastheemergenceofpandemic virusesandtheadaptationoforganismstonewenvironments.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
1R35GM126911-01
Application #
9483133
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Janes, Daniel E
Project Start
2018-07-17
Project End
2018-10-31
Budget Start
2018-07-17
Budget End
2018-10-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost

  Institution

Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109