Biology subjects

Lopez, R. C.

Publications and source records attributed to Lopez, R. C..

3 recordsLinked to original sources

bioRxiv2026

Engineered proteins to restore and enhance neurotransmitter release

Synapse dysfunction is a hallmark feature of many neurological diseases. Synaptic transmission is initiated in nerve terminals, where active zone protein complexes control vesicle fusion for neurotransmitter release. Here, we engineer proteins that mediate active zone functions and demonstrate their use for reconstituting and strengthening neurotransmission. A protein composed of CaV{beta}4 and the RIM1 zinc finger, {beta}4-Zn, restored neurotransmitter release after active zone disruption through recruitment of Munc13. We develop {beta}4-MC, derived from the Munc13-1 MUN and C2C domains, which bypasses Munc13 recruitment and directly mediates vesicle docking, priming and fusion after active zone disruption. In {beta}4-MC, MUN domain functions are dispensable for docking, but active MUN and C2C domains are both necessary for neurotransmitter release. In wild-type mouse and human neurons, {beta}4-MC but not {beta}4-Zn strengthens neurotransmitter release. Furthermore, {beta}4-Zn and {beta}4-MC restore and enhance dopamine release in the mouse striatum, respectively. Hence, {beta}4 proteins are engineered secretory proteins with therapeutic potential as enhancers of synaptic function.

neuroscience↗

bioRxiv2025

Imbalance in gut microbial interactions as a marker of health and disease

Imbalances in the human gut microbiome (dysbioses) are linked to multiple diseases but remain poorly understood. Current biomarkers to identify dysbiosis are inconsistent and fail to capture the ecological mechanisms differentiating healthy from diseased microbiomes. We propose a general dysbiosis biomarker, inspired by phenomenology observed in a gut-microbiome theoretical model introduced here. The emergent communities show complex interaction networks and two distinct collective states, corresponding to healthy and dysbiotic microbiomes. Our robust metric for dysbiosis, by quantifying the balance between cooperation and competition, differentiates these states in both simulated and real datasets across diverse diseases. Moreover, it reveals that dysbiosis results from a shift toward greater cooperation in the community. Our metric further correlates with disease progression, highlighting its potential as a diagnostic tool.

microbiology↗

bioRxiv2024

Innervation density governs crosstalk of GPCR-based norepinephrine and dopamine sensors

GPCR-based fluorescent sensors are widely used to correlate neuromodulatory signaling with brain function. While experiments in transfected cells often reveal selectivity for individual neurotransmitters, sensor specificity in the brain frequently remains uncertain. Pursuing experiments in brain slices and in vivo, we find that norepinephrine and dopamine cross-activate the respective sensors. Non-specific activation occurred when innervation of the cross-reacting transmitter was high, and silencing of specific innervation was indispensable for interpreting sensor fluorescence.

neuroscience↗