Biology subjects

Hurtado, J.

Publications and source records attributed to Hurtado, J..

23 records · Page 2Linked to original sources

bioRxiv2021

The unfolded protein response triggers the ancestral immune deficiency pathway

The insect immune deficiency (IMD) pathway is a defense mechanism that senses and responds to Gram negative bacteria. Ticks lack genes encoding upstream components that initiate the IMD pathway. Despite this deficiency, core signaling molecules are present and functionally restrict tick-borne pathogens. The molecular events preceding activation remain undefined. Here, we show that the Unfolded Protein Response (UPR) initiates the IMD network in Ixodes scapularis ticks. The endoplasmic reticulum (ER) stress receptor, IRE1, is phosphorylated in response to tick-borne bacteria, but does not splice the mRNA encoding XBP1. Instead, through protein modeling and reciprocal pulldowns, we show that Ixodes IRE1 complexes with TRAF2. Disrupting IRE1-TRAF2 signaling blocks IMD pathway activation and diminishes the production of reactive oxygen species. Through in vitro, in vivo, and ex vivo techniques we demonstrate that the UPR-IMD pathway circuitry limits the Lyme disease-causing spirochete Borrelia burgdorferi and the rickettsial agents Anaplasma phagocytophilum and A. marginale (anaplasmosis). Altogether, our study uncovers a novel linkage between the UPR and the IMD pathway in ticks.

immunology↗

bioRxiv2021

Research gaps and new insights in the intriguing evolution of Drosophila seminal proteins

While the striking effects that seminal fluid proteins (SFPs) exert on females are fairly conserved among Diptera, they exhibit remarkable evolutionary lability. Consequently, most SFPs lack detectable homologs among the repertoire of SFPs of phylogenetically distant species. How such a rapidly changing proteome "manages" to conserve functions across taxa is a fascinating question. However, this and other pivotal aspects of SFPs evolution remain elusive because discoveries on these proteins have been mainly restricted to the model D. melanogaster. Here, we provide an overview of the current knowledge on the inter-specific divergence of Drosophila SFPs and compile the increasing amount of relevant genomic information from multiple species. Capitalizing the accumulated knowledge in D. melanogaster, we present novel sets of high-confidence SFP candidates and transcription factors presumptively involved in regulating the expression of SFPs. We also address open questions by performing comparative genomic analyses that failed to support the existence of conserved SFPs shared by most dipterans and indicated that gene co-option is the most frequent mechanism accounting for the origin of Drosophila SFP-coding genes. We hope our update establishes a starting point to integrate, as more species are assayed for SFPs, further data and thus, to widen the understanding of the intricate evolution of these proteins.

evolutionary biology↗

bioRxiv2020

Rapid isolation of potent SARS-CoV-2 neutralizing antibodies and protection in a small animal model

The development of countermeasures to prevent and treat COVID-19 is a global health priority. In under 7 weeks, we enrolled a cohort of SARS-CoV-2-recovered participants, developed neutralization assays to interrogate serum and monoclonal antibody responses, adapted our high throughput antibody isolation, production and characterization pipeline to rapidly screen over 1000 antigen-specific antibodies, and established an animal model to test protection. We report multiple highly potent neutralizing antibodies (nAbs) and show that passive transfer of a nAb provides protection against high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs define protective epitopes to guide vaccine design.

immunology↗

bioRxiv2019

What does mitogenomics tell us about the evolutionary history of the Drosophila buzzatii cluster (repleta group)

The Drosophila repleta group is an array of more than 100 cactophilic species endemic to the \"New World\". The acquisition of the ability to utilize decaying cactus tissues as breeding and feeding sites is a key aspect that allowed the successful diversification of the repleta group in the American deserts. Within this group, the Drosophila buzzatii cluster is a South American clade of seven cactophilic closely related species in different stages of divergence, a feature that makes it a valuable model system for evolutionary research. However, even though substantial effort has been devoted to elucidating the phylogenetic relationships among members of the D. buzzatii cluster, the issue is still controversial. In effect, molecular phylogenetic studies performed to date generated ambiguous results since tree topologies depend on the kind of molecular marker employed. Curiously, even though mitochondrial DNA has become a popular marker in evolutionary biology and population genetics, none of the more than twenty Drosophila mitogenomes assembled so far belongs to this cluster. In this work we report the assembly of six complete mitogenomes of five species: D. antonietae, D. borborema, D. buzzatii, D. seriema and two strains of D. koepferae, with the aim to revisit the phylogenetic relationships and divergence times by means of a mitogenomic approach. The recovered topology using complete mitogenomes gives support to the hypothesis of the monophyly of that the D. buzzatii cluster and shows two main clades, one including D. buzzatii and D. koepferae (both strains) and the other the remaining species. These results are in agreement with previous reports based on a few mitochondrial and/or nuclear genes but in conflict with the results of a recent large-scale nuclear phylogeny, suggesting that nuclear and mitochondrial genomes depict different evolutionary histories.

evolutionary biology↗

bioRxiv2017

Combinatorial Drug Discovery in Nanoliter Droplets

Combinatorial drug treatment strategies perturb biological networks synergistically to achieve therapeutic effects and represent major opportunities to develop advanced treatments across a variety of human disease areas. However, the discovery of new combinatorial treatments is challenged by the sheer scale of combinatorial chemical space. Here we report a high-throughput system for nanoliter-scale phenotypic screening that stabilizes a chemical library in nanoliter droplet emulsions and automates the formulation of chemical combinations en mass using parallel droplet processing. We apply this system to predict synergy between more than 4,000 investigational and approved drugs and a panel of 10 antibiotics against E. coli, a model Gram-negative pathogen. We found a range of drugs not previously indicated for infectious disease that synergize with antibiotics. Our validated hits include drugs that synergize with the antibiotics vancomycin, erythromycin, and novobiocin, which are used against Gram-positive bacteria but are not effective by themselves to resolve Gram-negative infections.

bioengineering↗