Biology subjects

Ramiro, I. B. L.

Publications and source records attributed to Ramiro, I. B. L..

5 recordsLinked to original sources

bioRxiv2026

Prey-specific toxins provide broad venom activity in cephalopods

Cephalopods are among the oceans most sophisticated predators that use camouflage, complex behaviors, and venom to subdue a wide range of prey. However, the functional role of venom across diverse prey remains poorly understood, particularly whether cephalopods deploy venom to capture fish. Through comprehensive transcriptomic profiling of venom glands, we identify toxins with molecular signatures of prey-specific adaptation, including a previously unrecognized family of peptide toxins, octotensins, that evolved through convergent evolution to mimic the vertebrate hormone neurotensin. Functional assays and cryo-electron microscopy demonstrate that octotensins potently activate fish and human neurotensin receptor 1, engage this target in a near-identical manner to the chordate hormone, and induce acute hypotension in rodents. Together, our findings demonstrate that cephalopods achieve broad venom activity through phylum-specific toxins, including those targeting fish, revealing an evolutionary strategy by which generalist predators can capture phylogenetically diverse prey. One-Sentence SummaryCephalopod venom comprises prey-specific toxins, including neurotensin-mimicking peptides that target fish.

systems biology↗

bioRxiv2026

Mimics of the chordate gut-brain hormone neurotensin in parasitic intestinal hookworms

Hookworms of the family Ancylostomatidae are intestinal parasites that infect hundreds of millions of people worldwide, contributing to malnutrition, anemia, and impaired development. While hookworms are known to secrete immunomodulatory molecules to evade host defenses, it has been unclear whether they also exploit host hormonal signaling. Here, we identify a previously unrecognized family of hookworm peptides, which we term ancylotensins. Ancylotensins share strong sequence similarity with the chordate hormone neurotensin, a key regulator of metabolism, gut-brain communication, and intestinal function. In vitro pharmacological assays, ex vivo gut contractility studies, and cryo-electron microscopy demonstrate that ancylotensins closely replicate both the structural and functional properties of mammalian neurotensin to modulate gut function. Furthermore, ancylotensins do not share common ancestry with chordate neurotensin and instead evolved independently via convergent evolution. These findings reveal the existence of gut peptide mimicry as a mechanism by which intestinal parasites can manipulate host physiology.

biochemistry↗

bioRxiv2024

Venom-inspired somatostatin receptor 4 (SSTR4) agonists as new drug leads for peripheral pain conditions

Persistent pain affects one in five people worldwide, often with severely debilitating consequences. Current treatment options, which can be effective for mild or acute pain, are ill-suited for moderate-to-severe persistent pain, resulting in an urgent need for new therapeutics. In recent years, the somatostatin receptor 4 (SSTR4), which is expressed in sensory neurons of the peripheral nervous system, has emerged as a promising target for pain relief. However, the presence of several closely related receptors with similar ligand-binding surfaces complicates the design of receptor-specific agonists. In this study, we report the discovery of a potent and selective SSTR4 peptide, consomatin Fj1, derived from extensive venom gene datasets from marine cone snails. Consomatin Fj1 is a mimetic of the endogenous hormone somatostatin and contains a minimized binding motif that provides stability and drives peptide selectivity. Peripheral administration of synthetic consomatin Fj1 provided analgesia in mouse models of postoperative and neuropathic pain. Using structure-activity studies, we designed and functionally evaluated several Fj1 analogs, resulting in compounds with improved potency and selectivity. Our findings present a novel avenue for addressing persistent pain through the design of venom-inspired SSTR4-selective pain therapeutics. One Sentence SummaryVenom peptides from predatory marine mollusks provide new leads for treating peripheral pain conditions through a non-opioid target.

pharmacology and toxicology↗

bioRxiv2021

Reconstructing the Origins of a Neuropeptide Signaling System Using the Accelerated Evolution of Biodiverse Cone Snail Venoms

Somatostatin and its related peptides (SSRPs) form an important family of hormones with diverse physiological roles. The ubiquitous presence of SSRPs in vertebrates and several invertebrate deuterostomes suggests an ancient origin of the SSRP signaling system. However, the existence of SSRP genes outside of deuterostomes has not been established and the evolutionary history of this signaling system remains poorly understood. Our recent discovery of SSRP-like toxins (consomatins) in venomous marine cone snails (Conus) suggested the presence of a homologous signaling system in mollusks and potentially other protostomes. Here we identify the molluscan SSRP-like signaling gene that gave rise to the consomatin family. Following recruitment into venom, consomatin genes experience strong positive selection and repeated gene duplications resulting in the formation of a hyper-diverse family of venom peptides. Intriguingly, the largest number of consomatins was found in worm-hunting species (> 400 sequences), indicating a homologous system in annelids, another large protostome phylum. Comprehensive sequence mining enabled the identification of orthologous SSRP-like sequences (and their corresponding orphan receptor) in annelids and several other protostome phyla. These results establish the existence of SSRP-like sequences in many major branches of bilaterians, including xenacoelomorphs, a phylum believed to have emerged before the divergence of protostomes and deuterostomes, ~ 600 My ago. Finally, having a large set of predator-prey SSRP sequences available, we show that while the cone snails signaling SSRP-like genes are under purifying selection, in striking contrast, the consomatin genes experience rapid directional selection to target receptors in a changing mix of prey.

evolutionary biology↗

bioRxiv2021

Somatostatin venom analogs evolved by fish-hunting cone snails: From prey capture behavior to identifying drug leads

Somatostatin (SS) is a peptide hormone with diverse physiological roles. By investigating a deep-water clade of fish-hunting cone snails, we show that predator-prey evolution has generated a diverse set of SS analogs, each optimized to elicit specific systemic physiological effects in prey. The increased metabolic stability, distinct SS receptor activation profiles, and chemical diversity of the venom analogs make them suitable leads for therapeutic application, including pain, cancer and endocrine disorders. Our findings not only establish the existence of SS-like peptides in animal venoms, but also serve as a model for the synergy gained from combining molecular phylogenetics and behavioral observations to optimize the discovery of natural products with biomedical potential. One Sentence SummarySomatostatin drug design by fish-hunting cone snails

biochemistry↗