Biology subjects

Pineiro, A.

Publications and source records attributed to Pineiro, A..

4 recordsLinked to original sources

bioRxiv2026

Helix Design Studio: designing antimicrobial peptide candidates for membrane environments

The activity of many antimicrobial peptides (AMPs) depends on how their sequences interact with different membrane environments. This creates a design challenge: improving compatibility with a target environment can also favour interactions under conditions where activity is undesirable. Helix Design Studio is an open-source web application that addresses this challenge by analysing and designing peptide sequences on a prescribed -helical scaffold. A published environmental scoring framework combines intrinsic helix propensity, residue-pair interactions, electrostatics and hydrophobic exposure to evaluate the assumed helical state in idealized solvents and interfacial environments. A shared, sequence-dependent alignment rule links the amphipathic residue pattern to the interfacial geometry during both analysis and optimization. Users can inspect score contributions, generate candidate families and search for sequences that favour a target environment or balance compatibility across environments. Computational demonstrations show that environmental assumptions and helix orientation affect candidate rankings and sequence selection. Agreement with an independent descriptor implementation and exhaustive enumeration of a tractable sequence space support computational consistency. Downloadable sequences, scores and calculation settings provide reproducible starting points for simulation and experimental characterization. The scores assess model compatibility; they do not predict folding equilibria or establish biological selectivity. Helix Design Studio is freely available at https://helix.simbioslab.com/. Scientific Contribution. Helix Design Studio connects sequence analysis and candidate generation with explicit design objectives across solvent and interfacial environments. An interpretable scoring framework supports diverse peptide families, preferences for a target over competing environments and compromises between conditions; downloadable sequences, scores and calculation settings make the design choices reproducible.

bioinformatics↗

bioRxiv2026

Fructose Dendrimer-Based Poly Ionic Complexes for Glut5-Specific Intracellular Drug Delivery in Murine Brain

Glial cells play essential roles in maintaining neural tissue homeostasis and limiting the spread of injury-induced neuroinflammation, yet their dysfunction can also exacerbate neurodegenerative, neuroimmune, and neurodevelopmental disorders. Therapeutic targeting of specific glial cell populations would open up new treatment possibilities, but currently available viral and non-viral delivery vehicles are limited by carrier toxicity as well as poor delivery efficiency and specificity. To work towards new glia-targeted, non-viral delivery vehicles, we performed an in silico analysis on neural cell specific RNA-Seq datasets in mice to identify surface molecules differentially enriched on neurons, astrocytes, and microglia. We identified Slc2a5 (Glut5) as a microglia-enriched transporter and validated its microglia specific expression in healthy murine neural tissue using RNA in situ hybridization. By employing a sequential thiol-ene and enzymatic catalyzed reaction scheme, we synthesized polyelectrolytic dendrimers with multivalent presentation of fructose, the natural ligand for Glut5, and formulated nano-sized polyionic complexes (PICs) loaded with protein or nucleic acid cargo by mixing oppositely charged dendrimers. Fructose functionalized PICs lacking cationic surface charge enabled fructose-dependent intracellular protein delivery to Glut5-expressing human breast cancer cells (MCF-7) and mouse fibroblasts, while restricting uptake by Glut5-negative mouse astrocytes, confirming transporter-dependent selectivity in vitro. Fructose functionalized PICs resulted in minimal neuroinflammation when injected into mouse striatum at 1 mg/ml but elicited concentration-dependent neural tissue toxicity at higher doses. Fructose-PICs failed to achieve microglia specific intracellular delivery of functional proteins when injected into healthy neural tissue but aided in directing protein delivery to microglia and astrocytes at ischemic stroke lesions. Together, our findings demonstrate proof-of-principle for using in silico RNA-seq screening workflows to identify cell specific surfaceome targets and incorporating that insight into a modular biomaterial platform for targeted drug delivery.

bioengineering↗

bioRxiv2026

Environment-conditioned design of alpha-helical peptides

Designing peptide sequences that remain stable and selective across heterogeneous environments remains a central challenge in biomolecular modeling. Here we introduce an interpretable, physics-based Hamiltonian for environment-conditioned design of -helical peptide sequences. The model integrates helix propensities, pairwise interactions, electrostatics, anisotropic solvent exposure, and interfacial geometry into a unified energy function. To enable comparison across sequence lengths and environments, all contributions are rescaled and expressed as Z-scores relative to random sequence ensembles, yielding a normalized design landscape with balanced physical terms. This formulation defines a structured optimization problem that can be explored using exact, heuristic, and hybrid quantum- classical approaches without modification of the underlying model. The Hamiltonian recovers polar and apolar limits, discriminates experimentally characterized water-soluble and transmembrane -helical peptide sequences, and captures the preferential stabilization of membrane-active sequences at anionic interfaces over non-functional controls. It further enables multi-objective and selective design, generating candidate sequences with tunable environmental specificity.

biophysics↗

bioRxiv2022

Programmable Mixed-Signal Biocomputers in Mammalian Cells

Living cells perform sophisticated computations that guide them toward discrete states. Synthetic genetic circuits are powerful tools for programing these computations, where transcription-regulatory networks and DNA recombination are the two dominant paradigms for implementing these systems. While each strategy exhibits unique strengths and weaknesses, integrating both into one seamless design framework would enable advanced gene circuit designs intractable with either approach alone. Here, we present Computation via Recombinase Assisted Transcriptional Effectors (CREATE), which leverages site-specific recombination to perform robust logic on discreet computational layers and programmable transcription factors that connect these layers, allowing individual calculations to contribute toward larger operations. We demonstrate the functionality of CREATE by producing sophisticated circuits using a simple plug- and-play framework, including 189 2-input-3-output circuits, modular digital-to-analog signal converters, a 2-bit multiplier circuit, and a digital and analog mixed-signal generator. This work establishes CREATE as a versatile platform for programming complex signal processing systems capable of high-fidelity logic computation and tunable control over circuit output levels. One-Sentence SummaryWe present a minimal and robust genetic circuit platform for programming cells with sophisticated signal processing capabilities.

synthetic biology↗