Biology subjects

Galvao Ferrarini, M.

Publications and source records attributed to Galvao Ferrarini, M..

7 recordsLinked to original sources

bioRxiv2025

Unveiling the Unique Structure and Singular Function of the Histone Deacetylase 2 (TgHDAC2) of Toxoplasma gondii

Histone deacetylases (HDACs) are enzymes traditionally recognized for their role in removing acetyl groups from lysines on histones. However, recent findings have revealed that many HDACs also target non-histone proteins. In Toxoplasma gondii, although we identified TgHDAC2, an enzyme annotated as a class I HDAC, we found that its substrates are non-histone proteins. Notably, TgHDAC2 possesses two unique peptide insertions within its HDAC domain, whose structural and functional roles were previously unknown. Using cross-linking mass spectrometry (XLMS), we resolved the three-dimensional structure of TgHDAC2, while biophysical analyses demonstrated that these insertions do not compromise the proteins stability but play an important part in its function. Localization studies revealed differential expression of TgHDAC2 throughout the cell cycle, with prominent enrichment around daughter cells during mitosis and cytokinesis. Its deletion severely disrupts parasite replication, suggesting a critical role in cell cycle regulation. RNA sequencing of TgHDAC2 knockout parasites highlighted significant downregulation of genes involved in membrane composition, cytoskeletal organization, and cell signaling pathways, further supporting its role in modifying non-histone proteins. Collectively, our results suggest that TgHDAC2 acts as a deacetylase for non-histone proteins, modulating cytoskeletal and membrane proteins critical for T. gondii cell cycle progression and replication. IMPORTANCEToxoplasma gondii is an obligate intracellular parasite and a significant global public health concern. It is estimated that up to one-third of the worlds population may be infected, depending on the region, with even higher prevalence rates in South America due to the circulation of atypical and more virulent strains. Understanding the biology of this parasite and identifying novel therapeutic targets is therefore critical, as current treatments are outdated and ineffective against the chronic phase of toxoplasmosis. In this study, we identified a novel lysine deacetylase that plays an essential role in T. gondii replication, highlighting its potential as a promising therapeutic target.

microbiology↗

bioRxiv2024

Two distinct Trypanosoma eIF4F complexes co-exist, bind different mRNAs and are regulated during nutritional stress

Many eIF4F subunits and PABP paralogues are found in trypanosomes: six eIF4E, five eIF4G, one eIF4A and two PABPs. They are expressed simultaneously and assemble into different complexes, contrasting the situation in metazoans that use distinct complexes in different cell types or developmental stages. Each eIF4F complex has its own proteins, mRNAs and, consequently, a distinct function. We set out to study the function and regulation of the two major eIF4F complexes of Trypanosoma cruzi and identified the associated proteins and mRNAs of eIF4E3 and eIF4E4 in cells in exponential growth and in nutritional stress. Upon stress, eIF4G/eIF4A and PABP remain associated to the eIF4E, but the associations with other 43S pre-initiation factors decrease, indicating that ribosome attachment is impaired. Most eIF4E3-associated mRNAs encode for metabolic proteins, while eIF4E4 associate to mRNAs encoding ribosomal proteins. Interestingly, for both eIF4E3/4, more mRNAs were associated in stressed cells than in non-stressed cells, even though these mRNAs have lower translational efficiencies in stress. In summary, trypanosomes have two co-existing eIF4F complexes involved in translation of distinct mRNA cohorts important for growth. Under stress conditions, both complexes exit translation but remain bound to their mRNA targets.

molecular biology↗

bioRxiv2023

Coordination of host and endosymbiont gene expression governs endosymbiont growth and elimination in the cereal weevil Sitophilus spp.

BackgroundInsects living in nutritionally poor environments often establish long-term relationships with intracellular bacteria that supplement their diets and improve their adaptive and invasive powers. Even though these symbiotic associations have been extensively studied on physiological, ecological and evolutionary levels, few studies have focused on the molecular dialogue between host and endosymbionts to identify genes and pathways involved in endosymbiosis control and dynamics throughout host development. ResultsWe simultaneously analyzed host and endosymbiont gene expression during the life cycle of the cereal weevil Sitophilus oryzae, from larval stages to adults, with a particular emphasis on emerging adults where the endosymbiont Sodalis pierantonius experiences a contrasted growth-climax-elimination dynamics. We unraveled a constant arms race in which different biological functions are intertwined and coregulated across both partners. These include immunity, metabolism, metal control, apoptosis, and bacterial stress response. ConclusionsThe study of these tightly regulated functions, which are at the center of symbiotic regulations, provides evidence on how hosts and bacteria finely tune their gene expression and respond to different physiological challenges constrained by insect development in a nutritionally limited ecological niche. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=143 HEIGHT=200 SRC="FIGDIR/small/535335v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@800121org.highwire.dtl.DTLVardef@1ca2c25org.highwire.dtl.DTLVardef@183d56org.highwire.dtl.DTLVardef@163074f_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2022

Antimicrobial peptide secretion protects endosymbionts from bacteriome autoimmunity in insects

BackgroundMany insects house symbiotic intracellular bacteria (endosymbionts) that provide them with essential nutrients, thus promoting usage of nutrient-poor habitats. Endosymbiont seclusion within host specialized cells, called bacteriocytes, often organized in a dedicated organ, the bacteriome, is crucial in protecting them from host immune defenses while avoiding chronic host immune activation. Previous evidence obtained in the cereal weevil Sitophilus oryzae has shown that bacteriome immunity is activated against invading pathogens, suggesting endosymbionts might be targeted and impacted by immune effectors during an immune challenge. To pinpoint any molecular determinants associated with such challenges, we conducted a dual transcriptomic analysis of S. oryzaes bacteriome subjected to immunogenic peptidoglycan fragments. ResultsWe show that upon immune challenge the bacteriome actively participates in the innate immune response via an induction of antimicrobial peptides (AMPs). Surprisingly, endosymbionts do not undergo any transcriptomic changes, indicating that this potential threat goes unnoticed. Immunohistochemistry showed that TCT-induced AMPs are located outside the bacteriome, excluding direct contact with the endosymbionts. ConclusionsThis work demonstrates that endosymbiont protection during an immune challenge is mainly achieved by efficient confinement within bacteriomes, which provides physical separation between host systemic response and endosymbionts.

immunology↗

bioRxiv2021

The genome sequence of the cereal pest Sitophilus oryzae: an unprecedented transposable element content

BackgroundThe rice weevil Sitophilus oryzae is one of the most important agricultural pests, causing extensive damage to cereal in fields and to stored grains. S. oryzae has an intracellular symbiotic relationship (endosymbiosis) with the Gram-negative bacterium Sodalis pierantonius and is a valuable model to decipher host-symbiont molecular interactions. ResultsWe sequenced the Sitophilus oryzae genome using a combination of short and long reads to produce the best assembly for a Curculionidae species to date. We show that S. oryzae has undergone successive bursts of transposable element (TE) amplification, representing 72% of the genome. In addition, we show that many TE families are transcriptionally active, and changes in their expression are associated with insect endosymbiotic state. S. oryzae has undergone a high gene expansion rate, when compared to other beetles. Reconstruction of host-symbiont metabolic networks revealed that, despite its recent association with cereal weevils (30 Kyear), S. pierantonius relies on the host for several amino acids and nucleotides to survive and to produce vitamins and essential amino-acids required for insect development and cuticle biosynthesis. ConclusionsHere we present the genome of an agricultural pest beetle, which may act as a foundation for pest control. In addition, S. oryzae may be a useful model for endosymbiosis, and studying TE evolution and regulation, along with the impact of TEs on eukaryotic genomes.

genomics↗

bioRxiv2020

Phenotypic and transcriptomic responses to stress differ according to population geography in an invasive species

BackgroundAdaptation to rapid environmental changes must occur within a short time scale. In this context, studies of invasive species may provide insights into the underlying mechanisms of rapid adaptation as these species have repeatedly encountered and successfully adapted to novel environmental conditions. Here we investigated how invasive and non-invasive populations of D. suzukii deal with an oxidative stress at both the phenotypic and molecular level. We also investigated the impact of transposable element insertions on the differential gene expression between genotypes in response to oxidative stress. ResultsInvasive populations lived longer in the untreated condition than non-invasive Japanese populations. As expected, lifespan was greatly reduced following exposure to paraquat, but this reduction varied among genotypes (a genotype by environment interaction, GEI) with invasive genotypes appearing more affected by exposure than non-invasive genotypes. We also performed transcriptomic sequencing of selected genotypes upon and without paraquat and detected a large number of genes differentially expressed, distinguishing the genotypes in the untreated environment. While a small core set of genes were differentially expressed by all genotypes following paraquat exposure, much of the response of each population was unique. Interestingly, we identified a set of genes presenting genotype by environment interaction (GEI). Many of these differences may reflect signatures of history of past adaptation. Transposable elements (TEs) were not activated after oxidative stress and differentially expressed (DE) genes were significantly depleted of TEs. ConclusionIn the decade since the invasion from the south of Asia, invasive populations of D. suzukii have diverged from populations in the native area regarding their genetic response to oxidative stress. This suggests that such transcriptomic changes could be involved in the rapid adaptation to local environments.

genomics↗

bioRxiv2020

BrumiR: A toolkit for de novo discovery of microRNAs from sRNA-seq data.

MicroRNAs (miRNAs) are small non-coding RNAs that are key players in the regulation of gene expression. In the last decade, with the increasing accessibility of high-throughput sequencing technologies, different methods have been developed to identify miRNAs, most of which rely on pre-existing reference genomes. However, when a reference genome is absent or is not of high quality, such identification becomes more difficult. In this context, we developed BrumiR, an algorithm that is able to discover miRNAs directly and exclusively from sRNA-seq data. We benchmarked BrumiR with datasets encompassing animal and plant species using real and simulated sRNA-seq experiments. The results demonstrate that BrumiR reaches the highest recall for miRNA discovery, while at the same time being much faster and more efficient than the state-of-the-art tools evaluated. The latter allows BrumiR to analyze a large number of sRNA-seq experiments, from plants or animals species. Moreover, BrumiR detects additional information regarding other expressed sequences (sRNAs, isomiRs, etc.), thus maximizing the biological insight gained from sRNA-seq experiments. Finally, when a reference genome is available, BrumiR provides a new mapping tool (BrumiR2ref) that performs an a posteriori exhaustive search to identify the precursor sequences. The code of BrumiR is freely available at https://github.com/camoragaq/BrumiR.

bioinformatics↗