Project description:Blastocladiomycota, early diverging zoosporic (flagellated) lineages of fungi, are vastly understudied. This phylum includes the genus Coelomomyces which consists of more than eighty fungal species that are obligate parasites of arthropods. Coelomomyces lack a complete asexual life cycle, instead surviving through an obligate heteroecious alternation of generations life cycle. Despite their global distribution and interesting life cycle, little is known about Coelomomyces species. To begin to address this, we analyzed transcriptomes from across host-associated life stages including infection of larva and excised mature sporangia from the mosquito, Anopheles quadrimaculatus. We identified differentially expressed genes and over-enriched GO terms both across and within life stages and used these to make hypotheses about C. lativittatus biology. Generally, we found the C. lativittatus transcriptome to be a complex and dynamic expression landscape; GO terms related to metabolism and transport processes were over-enriched during infection and terms related to dispersal were over-enriched during sporulation. The C. lativittatus transcriptomes reported here are a valuable resource and may be leveraged toward furthering understanding of the biology of these and other early diverging fungal lineages.
Project description:To inhibitors for ADAR1 and a strong rationale for the development of ADAR1 p150 inhibitors for cancer immunotherapy Here, we describe AVA-ADR-001, a potential first-in-class small molecule inhibitor of ADAR1 p150 targeting the Z alpha domain. AVA-ADR-001 binds specifically to the Z alpha domain of ADAR1 p150 as confirmed by fluorescence spectroscopy and showed significant interferon induction in THP1 macrophages, which have high ADAR1 p150 expression compared with monocytes. Proteomics and transcriptomics analysis revealed significant upregulation of interferon signaling upon treatment with AVA-ADR -001. Interestingly, activation of interferon signaling resulted in AVA-ADR-001 induced cell killing in ADAR1-independent cell lines. In addition, treatment with AVA-ADR -001 resulted in significant activation of PKR, which may explain the decreased cell proliferation. Finally, AVA-ADR-001 showed superior anti-tumor efficacy compared to anti-PD1 in an in vivo tumor efficacy study and has a moderately synergistic effect when combined. Overall, this study reveals that ADAR1 p150 inhibition by AVA-ADR-001 exerts a multipronged impact on anti-tumor efficacy mediated by immune cells, accumulation of interferons and activation of PKR, resulting in protein translation inhibition and cell proliferation arrest.
Project description:Genomic resources enable study of the blastoclad fungus, Coelomomyces lativittatus, an obligate parasite of mosquitoes and microcrustaceans, during infection and sporulation
Project description:In 1976, a spontaneous mutant derived from Poncirus trifoliata (L.) Raf with short juvenile phase, namely, precocious trifoliate orange, was found in Yichang, Hubei province, China. Compared with 6 to 8 years of the wild-type trifoliate orange, almost all of the seedlings germinated from precocious trifoliate orange only have 1 to 2 years’ juvenile period, and 20% seedlings even flowered in the year after germination. Therefore, precocious trifoliate orange is an ideal material for studying the role of miRNAs involved in citrus juvenile and adult developmental stages. To characterize these miRNAs expressed at the juvenile and adult development stages of citrus, Affymetrix miRNA arrays were used to generate miRNA profiles of shoot meristems of trifoliate orange, the results revealed that some miRNAs were down-regulated expressed at adult stage compared with juvenile stage. Detailed comparison of the expression patterns of miRNAs and corresponding target genes revealed the negative correlation between them, while few of them are positively correlated.