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Rollins, R.

Publications and source records attributed to Rollins, R..

2 recordsLinked to original sources

The road to nowhere: geolocation-by-genotype traces large-scale yellow-browed warbler vagrancy to central Siberia

Vagrant animals - individuals found far outside their normal range - offer powerful natural experiments for understanding migratory mechanisms. The yellow-browed warbler (Phylloscopus inornatus) provides perhaps the best-yet example, typically migrating from Siberia to South/Southeast Asia yet found in increasingly large numbers in Western Europe. This represents a strikingly unresolved evolutionary puzzle: why do so many migrants consistently move in almost the complete wrong direction? A critical first step toward solving this enigma is determining where these birds come from. If vagrants came from the proximal western range edge this would imply simple disorientation, whilst a more easterly origin could imply large-scale reverse misorientation. Here, we develop a geolocation-by-genotype algorithm for low-coverage whole-genome resequencing data collected from feathers. Our method identifies spatially informative SNPs; clusters them to account for covariance in allele frequency through space; and employs a bootstrapped maximum-likelihood framework to estimate spatial origin with uncertainty. Applied to more than 80 European-caught birds, our results place their origin in central Siberia (118{degrees}E; 89-134{degrees}E [95% CI]); over 2000km east of the western range edge. These results suggest mass misorientation in a near-reverse direction, and highlight the yellow-browed warbler as an exceptional system for probing the mechanism, ontogeny and evolution of migration.

animal behavior and cognition↗

KDM5 demethylases suppress R-loop-mediated viral mimicry and DNA damage in breast cancer cells

Tumors with low expression of Interferon-Stimulated Genes (ISG) and Antigen Presentation (AP) genes respond relatively poorly to current immunotherapies. One of the early hallmarks of cancer is DNA hypomethylation in genomic repeat regions, resulting in the expression of normally silenced endogenous "viral" elements. Such epigenetic changes have the potential to augment anti-tumor immune responses as well as reduce tumor cell fitness through the generation of aberrant nucleic acid species (NAS) and consequent activation of NAS-sensing pathways. Therefore, tumor evolution should favor additional selective events that suppress NAS generation, possibly yielding specific therapeutic vulnerabilities. Here, we show that the Lysine Demethylase 5 (KDM5) family of epigenetic regulatory enzymes suppress R-loop formation in genomic repeat regions in cancer cells. We find that KDM5 inhibition in luminal breast cancer cells results in R-loop-mediated DNA damage, reduced cell fitness and an increase in ISG and AP signatures as well as cell surface Major Histocompatibility Complex (MHC) class I, mediated by RNA:DNA hybrid activation of the CGAS/STING pathway. KDM5 inhibition does not result in DNA damage or activation of the CGAS/STING pathway in normal breast epithelial cells, suggesting that KDM5 inhibitors may enable a wide therapeutic window in this setting, as compared to STING agonists or Type I Interferons. These findings provide new insights into the interplay between epigenetic regulation of genomic repeats, R-loop formation, innate immunity, and cell fitness in the context of cancer evolution and therapeutic vulnerability.

cancer biology↗