Biology subjects

Persello, A.

Publications and source records attributed to Persello, A..

3 recordsLinked to original sources

bioRxiv2026

In vivo optical induction of INaL by photoactivation of AaH-II peptide in beating heart using wireless implantable device

Precise spatiotemporal control of pharmacological compounds in cardiac tissue remains an unmet challenge. Systemic drug administration poorly reproduces the localized and transient nature of cardiac events. Photopharmacology, in which light controls drug activity, offers a compelling solution, but its translation to the beating heart requires wireless light delivery to a moving, soft, and electrically active organ. Here, we demonstrate the first in vivo use of a wireless device to photoactivate a peptide that modulates cardiac excitability. Using a flexible, battery-free implantable optoelectronic device, we achieved light-triggered uncaging of AaH-II*, a natural peptide that enhances the late sodium current. We first validated the caged peptide in vitro and ex vivo, showing that caging suppresses its activity and that UV illumination rapidly restores it. In vivo, wireless photoactivation produced a clear modulation of cardiac electrical activity, as monitored by electrocardiography. This work establishes device-based peptide photomodulation as a strategy for remote, temporally controlled pharmacological intervention in the heart. More broadly, it provides a new platform for probing cardiac excitability and developing region-targeted therapies.

pharmacology and toxicology↗

bioRxiv2024

A missense mutation in the gene encoding the Mg-chelatase subunit I leads to a viable pale green line with phenotypic features of potential interest for barley breeding programs

The pale green trait, i.e. reduced chlorophyll content, has been shown to increase the efficiency of photosynthesis and biomass accumulation when photosynthetic microorganisms and tobacco plants are cultivated at high densities. Thus, the hus1 barley mutant is defective in photosystem antenna biogenesis, and exhibits a 50% reduction in leaf chlorophyll content. Nevertheless, its agronomical performance under standard field conditions is comparable to that of the wild-type. This supports the notion that crops can decrease their investment in antenna proteins and chlorophyll biosynthesis without detrimental effects on productivity. Here, we assess the effects of reducing leaf chlorophyll content in barley by altering the chlorophyll biosynthesis pathway (CBP). To this end, we have isolated and characterised the pale green barley mutant xan-h.chli-1, which carries a missense mutation in the Xan-h gene for subunit I of Mg-chelatase (HvCHLI), the first enzyme in the CBP. Intriguingly, xan-h.chli-1 is the only known viable homozygous mutant at the Xan-h locus in barley. The Arg298Lys amino-acid substitution in the ATP-binding cleft causes a slight decrease in HvCHLI protein abundance, and a marked reduction in Mg-chelatase activity. Under controlled growth conditions, mutant plants display reduced accumulation of antenna and photosystem core subunits, together with reduced photosystem II yield relative to wild type under moderate illumination, and consistently higher than wild-type levels at high light intensities. Moreover, the reduced content of leaf chlorophyll is associated with a stable reduction in daily transpiration rate, and slight decreases in total biomass accumulation and water-use efficiency. These traits are reminiscent of phenotypic features of wild barley accessions and landraces that thrive under arid climatic conditions. Overall, our findings make the xan-h.chli-1 allelic variant of potential interest for tailoring barley, and other crop plants, for growth in harsh environments.

plant biology↗

bioRxiv2023

Optical control of cardiac rhythm by in vivo photoactivation of an ERG channel peptide inhibitor

RATIONALECardiac rhythm, conduction and synchronization of electrical activity require the coordinated action of different types of ion channels that differ according to transmural and regional specificities. Classical pharmacology affects these ion channels in a non-regionalized way which explains why treating arrhythmias, that often occur in specific foci, has often limited efficacy in addition to negative side-effects on non-targeted organs. Photopharmacology is an emergent technology that has the potential to counteract all the negative aspects of classical pharmacology by restricting drug activity in a spatio-temporal manner. OBJECTIVEWe tested the potential of photopharmacology in specifically regulating heart activity by using a caged derivative of a natural peptide inhibitor of the ERG channel, BeKm1. The peptide was uncaged and activity monitored in vitro on a cell line expressing the hERG channel, on human cardiomyocytes derived from iPS cells, and ex vivo and in vivo on zebrafish larvae and rat hearts. METHODS AND RESULTSCaged BeKm-1 is inactive and fully active upon uncaging. Uncaging of the peptide on human iPS-derived cardiomyocytes enlarges the action potential duration and triggers arrhythmias. Uncaging also triggers bradycardia and disturbs cardiac conduction within the atria in perfused rat hearts upon illumination. The potency of photopharmacology for cardiac electrical modulation was further validated in zebrafish larvae where illumination of the caged compound induces bradycardia and atrio-ventricular desynchrony. Finally, in anesthetized rats, illumination of the caged peptide in the right atria, containing the sino-atrial node, leads to bradycardia without arrhythmia. CONCLUSIONSThis report demonstrates that photopharmacology, using the caged peptide strategy, can be used for dynamically regulating cardiac electrical activity in vivo and that spatial illumination restriction can dissociate the bradycardic effect from the arrhythmic one. The technology is applicable to all kinds of cardiac ion channels and regions of interest to create arrhythmogenic models or investigate new clinical applications.

pharmacology and toxicology↗