The Daugherty lab in the Division of Biological Sciences at UCSD uses comparative genomics, biochemistry and virology to understand how host immunity genes evolve to defend against pathogens and how pathogens counter-evolve to defeat host immunity.
Daugherty Lab @ UCSD
News:
June 2025: Liz and Sofia head into the next step in their careers. Liz leaves to start a job as an Assistant Teaching Professor at University of Minnesota and Sofia is off to the MCB PhD program at UC Berkeley. Congrats and best of luck to you both!
February 2025: Dustin’s paper on innate immune recognition of short 5’ UTRs as a “non-self” mRNA pattern is now posted on bioRxiv! This has been a fun story to pull apart, starting with finding that two ISGs (IFIT2 and IFIT3) have potent antiviral activity against VSV. From there, we worked with Brian Cook, Kevin Corbett and Mark Herzik to determining the IFIT2-IFIT3 heterodimer structure by cryo-EM and worked with Eric Van Nostrand and Gene Yeo to map that the IFIT2-IFIT3 complex binds to the 5’ UTR of VSV mRNAs. The mapping was the key to discovering that IFIT2-IFIT3 is able to selectively inhibit translation of mRNAs that have short (<50 nt) 5’ UTRs. This is exciting, since many viral mRNAs (but few host transcripts) have short 5’ UTRs, which makes this a new molecular pattern that can distinguish non-self from self mRNAs, and allowed Dustin to extend IFIT2-IFIT3 antiviral activity to many more viruses. This one truly took a village; many Daugherty lab members (current, rotation students, and alumni) and a number of important collaborators teamed up to make this possible. Congrats to all!
January 2025: Andy’s paper describing the role of antiviral PARP proteins in the interferon-gamma response is now published in Science Advances! This is the culmination of Andy’s fantastic PhD work on PARP protein evolution, biochemical function, and role in the antiviral response. This is a tour de force, showing that some human PARPs directly ADP-ribosylate alphaviral proteins and inhibit viral replication, that alphaviral macrodomains reverse those modifications and oppose the PARP-mediated antiviral function, and that the entire subfamily of zinc-finger PARPs (PARPs 7, 12, and 13) are all required for the antiviral activity of interferon-gamma against alphaviruses. Answers a number of questions but also raises many new exciting ones about PARPs and antiviral immunity. Huge congratulations to Andy!
