Biology subjects

Lopes, D.

Publications and source records attributed to Lopes, D..

5 recordsLinked to original sources

bioRxiv2026

Coupling of tubulin acetylation to microtubule stabilization through molecular mimicry

Microtubules support diverse cellular functions through regulation by microtubule-associated proteins and tubulin post-translational modification, yet how these two layers are mechanistically integrated remains unclear. -tubulin acetylation marks mechanically resilient microtubules, and its incorporation in defined microtubule sub-populations is not well understood. Here, we identify MTCL1 as a molecular link between microtubule stabilization and post-translational modification installation. We find that MTCL1 stabilizes microtubules and alters the luminal surface when copolymerized with tubulin, remodeling -tubulin and enhancing TAT-mediated tubulin acetylation through molecular mimicry. This effect depends on assembly history and is not observed in pre-assembled microtubules. Targeted deletion of MTCL1 in zebrafish impacts axonal organization, leading to motor defects and increased seizure susceptibility. These findings establish MTCL1 as a licensing factor that couples microtubule stabilization with acetylation to regulate neuronal function.

biophysics↗

bioRxiv2026

A Mediator-dependent hypertranscriptional program governs neural stem cell fate decisions in vivo

Hypertranscription, a global increase in transcriptional output, is a defining feature of stem cells, but its biological relevance and regulation in vivo remain unclear. Using Drosophila neural stem cells (neuroblasts), we investigate the function and regulation of hypertranscription. Neuroblasts exhibit higher transcriptional activity than their differentiated progeny, establishing them as a model of hypertranscriptional stem cells. We identify the Mediator complex as a key regulator of this elevated transcriptional state. Mediator is broadly enriched across neuroblast chromatin, and its depletion causes a substantial, selective reduction in transcription in neuroblasts, with only mild effects in differentiated cells. Functionally, Mediator depletion impairs lineage progression, causing an accumulation of undifferentiated, stem-like cells, highlighting the necessity of hypertranscription for proper stem cell fate and differentiation. Finally, we show that Drosophila brain tumor neuroblasts exhibit an exaggerated, Mediator-dependent hypertranscriptional program. These findings establish Mediator as a central regulator of hypertranscription in both normal and tumorigenic neural stem cells, crucial for neural differentiation and stem cell fate progression.

developmental biology↗

bioRxiv2025

Uncovering the genetic diversity of the malaria parasite antigen MSP2 across Sub-Saharan Africa

Genetic diversity in Plasmodium falciparum poses a significant challenge to malaria control and elimination. This is particularly important for developing fully efficacious vaccines, which should include valuable blood stage antigens. Several antigen candidates are highly diverse and require further understanding. We surveyed the genetic diversity of the highly polymorphic merozoite surface protein 2 (MSP2) in 2761 P. falciparum isolates collected across Sub-Saharan Africa. Using PCR-based genotyping and long-read sequencing, we identified extensive diversity among msp2 size variants and sequences. Some size variants were more prevalent than others across different geographical regions, transmission intensities, and time points. These variants comprised multiple unique sequences, of which several were geographically and temporally widespread. Our study reveals greater msp2 sequence diversity than previously known, while also identifying interesting similarities in sequence and gene length across Sub-Saharan Africa. These findings support the further exploration of common msp2 variants in relation to parasite virulence and vaccine development.

microbiology↗

bioRxiv2025

Tau-seed interactome analysis reveals distinct functional signatures in Alzheimer's disease across model systems.

Tau aggregates propagate through the brain in a prion-like manner in Alzheimers disease (AD) and other tauopathies, but the molecular identity and functional partners of the seeding-competent Tau species remain poorly defined. Here, we present an unbiased proteomic profiling of a high-molecular-weight (HMW) Tau-seed isolated from AD patient brains. We contrast this interactome with that of a biochemically similar, seeding-incompetent HMW-Tau species from age-matched healthy controls. Despite comprising less than 5% of total Tau in the brain, Tau-seed associates with a distinct set of proteins enriched in synaptic, mitochondrial, and vesicle-trafficking functions. Cross-species functional screening in Drosophila and mouse models identifies interactors that modulate Tau toxicity and seeding. Spatially resolved analysis of postmortem AD brains reveals heterogenous co-deposition of these proteins with Tau aggregates, suggesting functionally distinct Tau-seed complexes. Together, this dataset provides a framework for understanding selective Tau-seed toxicity and identifies candidate regulators of Tau propagation with therapeutic potential.

neuroscience↗

bioRxiv2021

Photosynthesis from stolen chloroplasts increases sea slug reproductive fitness

Some sea slugs are able to steal functional chloroplasts (kleptoplasts) from their algal food sources, but the role and relevance of photosynthesis to the animal host remain controversial. While some researchers claim that kleptoplasts are slowly digestible snacks, others advocate that they enhance the overall fitness of sea slugs much more profoundly. Our analysis show light-dependent incorporation of 13C and 15N in the albumen gland and gonadal follicles of the sea slug Elysia timida, representing translocation of photosynthates to kleptoplast-free reproductive organs. Long-chain polyunsaturated fatty acids with reported roles in reproduction were produced in the sea slug cells using labelled precursors translocated from the kleptoplasts. Finally, we report reduced fecundity of E. timida by suppressing kleptoplast photosynthesis. The present study provides the first thorough experimental evidence that photosynthesis enhances the reproductive fitness of kleptoplast-bearing sea slugs, confirming the biological relevance of this remarkable association between a metazoan and an algal-derived organelle. TeaserSea slugs incorporate functional chloroplasts from algae and use products of photosynthesis to maximize reproductive output.

ecology↗