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Paz, A.

Publications and source records attributed to Paz, A..

2 recordsLinked to original sources

Effects of arthropod prey turnover on the chemical traits of poison frogs: a landscape ecology approach to assess the phenotypic consequences of biotic interactions

Ecological studies of species pairs demonstrated that biotic interactions promote phenotypic change and eco-evolutionary feedbacks. However, we have a limited understanding of how phenotypes respond to interactions with multiple taxa. We investigate how interactions with a network of prey species contribute to spatially structured variation in the skin toxins of the Neotropical poison frog Oophaga pumilio. Specifically, we assess how beta-diversity of alkaloid-bearing arthropod prey assemblages (68 ant species) and evolutionary divergence among populations (from a neutral genetic marker) contribute to frog poison dissimilarity (toxin profiles composed of 230 different lipophilic alkaloids sampled from 934 frogs at 46 sites). We show that ant assemblage turnover predicts alkaloid turnover and unique toxin combinations across the range of O. pumilio. By contrast, evolutionary relatedness is barely correlated with toxin variation. We discuss how the analytical framework proposed here can be extended to other multi-trophic systems, coevolutionary mosaics, microbial assemblages, and ecosystem services.

ecology

Discovery of tumoricidal DNA aptamers by effect-directed in-vitro evolution

Our current model of drug discovery is challenged by the relative ineffectiveness of drugs against highly variable and rapidly evolving diseases and their relatively high incidence of adverse effects due to poor selectivity. Here we describe a robust and reproducible platform which could potentially address these limitations. The platform enables rapid, de-novo discovery of DNA oligonucleotides evolved in-vitro to exert specific biological effects on target cells. Unlike aptamers, which are selected by their ligand binding capacity, this platform is driven directly by therapeutic effect and selectivity towards target vs negative target cells. The process could, therefore, operate without any a-priori knowledge (e.g. mutations, biomarker expression, or known drug resistance) of the target. We report the discovery of DNA oligonucleotides with direct and selective cytotoxicity towards several tumor cell lines as well as primary, patient-derived solid and hematological tumors, some with chemotherapy resistance. Oligonucleotides discovered by this platform exhibited favorable biodistribution in animals, persistence in target tumors up to 48 hours after injection, and safety in human blood. These oligonucleotides showed remarkable efficacy in-vivo as well as ex-vivo in freshly obtained, 3D cultured human tumors resistant to multiple chemotherapies. With further improvement, these findings could lead to a drug discovery model which is target-tailored, mechanism-flexible, and nearly on-demand.

synthetic biology