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Biology subjects

De Giorgi, M.

Publications and source records attributed to De Giorgi, M..

2 recordsLinked to original sources

Electrically programmable picoscale phototransduction of a newly discovered microbial rhodopsin

Human retina can achieve single-photon sensitivity through specialised photoreceptors that convert light into electrical signals via phototransduction. Among microbial light-sensitive proteins, proteorhodopsins stand out for their intrinsic light-driven ion transport and spectral tunability, making them promising candidates for bio-inspired photonic devices. A central challenge for acellular integration, however, is the fragility of most bacterial rhodopsins under extreme conditions. Here, we exploit the exceptional robustness of TARA76, a microbial rhodopsin that retains structural integrity even upon complete dehydration, to demonstrate its functional reconstitution in an artificial black lipid membrane within a biocompatible microfluidic platform. By recording light-induced ionic currents with picoampere sensitivity across a broad range of pH, illumination power, electrolyte composition, and applied voltages, we establish TARA76 as a high-performance photoelectric transducer in a fully acellular environment. Strikingly, we uncover a strong and previously unreported dependence of the photocurrent on Na+ ions, which appears to play a key structural and functional role in stabilising the proteins active conformation. Furthermore, we demonstrate that the orientation of TARA76 within the artificial membrane can be externally controlled by applying a defined electric field during bilayer formation, enabling deterministic tuning of photocurrent directionality. Together, these results establish a robust and miniaturisable bio-photonic platform with direct implications for quantum light sensing, neuromorphic bioelectronics, and next-generation artificial retinal interfaces.

biophysics↗

In vivo expansion of gene-targeted hepatocytes through transient inhibition of an essential gene

Homology Directed Repair (HDR)-based genome editing is an approach that could permanently correct a broad range of genetic diseases. However, its utility is limited by inefficient and imprecise DNA repair mechanisms in terminally differentiated tissues. Here, we tested "Repair Drive", a novel method for improving targeted gene insertion in the liver by selectively expanding correctly repaired hepatocytes in vivo. Our system consists of transient conditioning of the liver by knocking down an essential gene, and delivery of an untargetable version of the essential gene in cis with a therapeutic transgene. We show that Repair Drive dramatically increases the percentage of correctly targeted hepatocytes, up to 25%. This resulted in a five-fold increased expression of a therapeutic transgene. Repair Drive was well-tolerated and did not induce toxicity or tumorigenesis in long term follow up. This approach will broaden the range of liver diseases that can be treated with somatic genome editing.

genetics↗