An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human Disease #GWAS of cells of 528 people + 8 pathogens. Discoveries between CXCL10 and #IBD; ZBTB20 and #Chlamydia, #HCV. Portal to link your gene to traits

Thanks for reading! This has been a such a fun project with Angela and others including @wallacewly @AKSanRoman We’re excited now to apply this same approach to sex differences in different contexts, tissues, infection models and other instances of G x E interaction (6/6).

The result is a catalog of sb-eQTL that is highly enriched for loci associated with complex sex-biased traits and diseases such as body height and multiple sclerosis. Here’s an example of an eQTL only in males that colocalizes with GWAS signal for MS (5/6)

We break with current dogma by showing sex-biased eQTL are abundant, through a two-step computational framework that has increased the number of sb-eQTL by ~30-fold with greater replication than in previous studies (4/6)

We integrate TF ChIP-seq with deep neural network modelling to identify key TFs that impact sex biased expression, model the impact of sex-biased expression of these TFs on targets, and validate findings based on empirical data (3/6)

Using our single-cell GWAS platform (scHi-HOST) with 240 male and 240 female LCLs, sex chromosomes provides a direct explanation for a minority of genes with sex-biased expression 7.7%, the great majority are targets of transcription factors with sex-biased expression 79% (2/6)

What causes differences in biological sex? In our latest preprint, @_AngelaJones takes our lab in a new direction, revealing mechanisms of sex-biased gene expression and identifying abundant sex-biased eQTL throughout the genome (1/6)

RT @wallacewly: Finally out! We found ferroptosis inhibition reverse aging-exacerbated liver damage, and a gene signature tracks MASLD live….

Ko lab grad students Rachel Keener, Trisha Dalapati, and Margaret Gaggioli at #ASMMicrobe2024 .Say hi if you see them around and want to learn more about Salmonella effectors, human genetics of plague, or shared genetics of COVID and IPF

Ko lab mini-golf (and taco-eating) team

RT @popp_josh: SO excited to share our recent work!. To better understand the molecular impacts of human genetic variation, we need models….

Broad-ranging and thoughtful article by @HannahThomasy about genetic susceptible/resistance to infection. Fun to see our work put in perspective with others including @EllenLeffler 's brilliant malaria work. More “superpower” human genetic variants coming soon from Hi-HOST.

Ko Lab art team visiting the @NasherMuseum on a beautiful day in Durham

RT @ImmunologyDuke: Congratulations to David @TobinLab from @DukeMGM and lIB for their election as a fellow of the AAM. Well deserved honor….

Congrats to first author PhD candidate @m_gaggioli and wonderful collaborators including @_AngelaJones @erica_washi and the @ThurstonLab who continue their own studies of SarA/SteE but generously shared their expertise to help test the ideas in this paper.

The isoleucine is conserved across 4000 Salmonella isolates and matches the isoleucine in the GSK3 autophosphorylation site. SarA evolved to serve as an optimal substrate for GSK3, a kinase unique in high baseline activity, resulting in supraphysiological activation of STAT3.

SarA activates STAT3 more than IL-6/gp130, biasing transcriptional response towards anti-inflammatory targets. This is not due to lack of binding sites for negative regulators or greater affinity for STAT3, but an isoleucine in the SarA YxxQ motif makes it a better GSK3 substrate.

Previously our lab and @ThurstonLab demonstrated that SarA activates STAT3 through a region similar to the cytokine co-receptor gp130 that is tyrosine phosphorylated by GSK3. But why does Salmonella have an effector turn on STAT3 when it is already being activated by cytokines?.

Our latest preprint shows that how strongly a bacterial effector activates its host target is critical: “A single amino acid in the Salmonella effector SarA/SteE triggers supraphysiological activation of STAT3 for anti-inflammatory target gene expression”

Ko lab holiday party with secret Santa and cookie decorating

RT @mraffatellu: Hi everyone, my wonderful former PhD student Vladimir Diaz-Ochoa (@vdiazochoa) was diagnosed with ALS. Vlad and his family….