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 2023: Lennice’s review on evolution of CARD8 and NLRP1 tripwires is now published in Current Opinion in Immunology! This is a fast moving field, and Lennice nicely summarizes what we know, and all of the interesting potential directions this might go. Congrats Lennice!
June 2023: Brian Tsu’s CARD8 paper is now published in PLoS Biology! We describe another innate immune ‘tripwire’ for viral proteases (as in Tsu et al., 2021), this time with the inflammasome sensor protein CARD8. We found CARD8 has evolved to sense protease activity from coronaviruses (CoVs), and results in inflammasome activation and cell death upon infection with pandemic (SARS-CoV-2) and seasonal (hCoV-229E) viruses. CARD8, not surprisingly, is fast evolving and we found that the bat CARD8 inflammasome is inhibited rather than activated by CoV proteases. Even wilder, we found a SNP in humans that switches the specificity of CARD8 from sensing CoVs to sensing enterovirus (e.g. rhinovirus) infection. Huge thanks to many other labs involved, especially (former baymate) Patrick Mitchell’s lab at UW. And huge congratulations to first author Brian Tsu! Original bioRxiv post from October 2022 is here.
May 2023: Sofia Delgado-Rodriguez’s macrodomain evolution paper is now published in Pathogens for their special edition on ADP-ribosylation in host-pathogen interactions! For a while now, we’ve been thinking about macrodomains, the enzymatic domain that can remove ADP-ribosylation from proteins, since they are found in rapidly evolving PARP proteins and in the non-structural proteins of alphaviruses and coronaviruses. Interestingly, many macrodomains can’t actually catalyze the removal of ADP-ribose. So we decided to see which PARP macrodomains and viral macrodomains are enzymatically active. Surprisingly, we found within mammals and within alphaviruses that this catalytic activity has been lost several independent times. Very strange, but also further evidence for the host-virus battle over ADP-ribosylation! Congrats to Sofia and Andy for getting this out there!
April 2023: Chinmay Kalluraya’s IRBP evolution paper is now published in PNAS! We found that a key protein involved in the vertebrate eye originated as a horizontal gene transfer (HGT) event from bacteria. Another striking example of how microbial genes have shaped our evolution. Congratulations to first author Chinmay Kalluraya, who discovered this and several other interesting cases of bacteria->metazoan HGT still to be published. This has also garnered some nice press since evolution of the eye has been such a longstanding mystery (even to Charles Darwin), including a nice write-up at Science by Elizabeth Pennisi here.
