Lab

Máté Varga's Lab


About the lab

The main focus of our group is the modelling of different rare, monogenic human diseases using zebrafish. We are especially interested in diseases linked to pseudouridylation defects and diseases resulting from the dysfunction of RecQ helicase orthologs.

We are also interested in developing paradise fish into a new(is) complementary model species of evodevo and behavioural genetics.

Featured research (18)

Small nucleolar RNAs (snoRNAs) are one of the most abundant and evolutionary ancient group of functional non-coding RNAs. They were originally described as guides of post-transcriptional rRNA modifications, but emerging evidence suggests that snoRNAs fulfil an impressive variety of cellular functions. To reveal the true complexity of snoRNA-dependent functions, we need to catalogue first the complete repertoire of snoRNAs in a given cellular context. While the systematic mapping and characterization of “snoRNAomes” for some species have been described recently, this has not been done hitherto for the zebrafish (Danio rerio). Using size-fractionated RNA sequencing data from adult zebrafish tissues, we created an interactive “snoRNAome” database for this species. Our custom-designed analysis pipeline allowed us to identify with high-confidence 67 previously unannotated snoRNAs in the zebrafish genome, resulting in the most complete set of snoRNAs to date in this species. Reanalyzing multiple previously published datasets, we also provide evidence for the dynamic expression of some snoRNAs during the early stages of zebrafish development and tissue-specific expression patterns for others in adults. To facilitate further investigations into the functions of snoRNAs in zebrafish, we created a novel interactive database, snoDanio, which can be used to explore small RNA expression from transcriptomic data.
The maternal-effect mutation ichabod (ich) results in ventralized zebrafish embryos due to impaired induction of the dorsal canonical Wnt-signaling pathway. While previous studies linked the phenotype to reduced ctnnb2 transcript levels, the causative mutation remained unidentified. Using long-read sequencing, we discovered that the ich phenotype stems from the insertion of a non-autonomous CMC-Enhancer/Suppressor-mutator (CMC-EnSpm) transposon in the 3'UTR of the gene. Through reporter assays, we demonstrate that while wild type ctnnb2 mRNAs exhibit remarkably high stability throughout the early stages of development, the insertion of the transposon dramatically reduces transcript stability. Genome-wide mapping of the CMC-EnSpm transposons across multiple zebrafish strains also indicated ongoing transposition activity in the zebrafish genome. Our findings not only resolve the molecular basis of the ich mutation but also highlight the continuing mutagenic potential of endogenous transposons and reveal unexpected aspects of maternal transcript regulation during early zebrafish development.
Small nucleolar RNAs (snoRNAs) are one of the most abundant and evolutionary ancient group of functional non-coding RNAs. They were originally described as guides of post-transcriptional rRNA modifications, but emerging evidence suggests that snoRNAs fulfil an impressive variety of cellular functions, some of which are only being discovered. To reveal the true complexity of snoRNA-dependent functions, we need to catalogue first the complete repertoire of snoRNAs in a given cellular context. While the systematic mapping and characterization of 'snoRNAomes' for some species have been described recently, this has not been done hitherto for the zebrafish ( Danio rerio ). Using size-fractionated RNA sequencing data from adult zebrafish tissues, we created an interactive 'snoRNAome' database for this species. Our custom-designed analysis pipeline allowed us to identify with high-confidence 68 previously unannotated snoRNAs in the zebrafish genome, resulting in the most complete set of snoRNAs to date in this species. Reanalyzing multiple previously published datasets, we also provide evidence for the dynamic expression of some snoRNAs during the early stages of zebrafish development and tissue-specific expression patterns for others in adults. To facilitate further investigations into the functions of snoRNAs in zebrafish, we created a novel interactive database, snoDanio, which can be used to explore small RNA expression from transcriptomic data.
Amongst fishes, zebrafish (Danio rerio) has gained popularity as a model system over most other species and while their value as a model is well documented, their usefulness is limited in certain fields of research such as behavior. By embracing other, less conventional experimental organisms, opportunities arise to gain broader insights into evolution and development, as well as studying behavioral aspects not available in current popular model systems. The anabantoid paradise fish (Macropodus opercularis), an “air-breather” species has a highly complex behavioral repertoire and has been the subject of many ethological investigations but lacks genomic resources. Here we report the reference genome assembly of M. opercularis using long-read sequences at 150-fold coverage. The final assembly consisted of 483,077,705 base pairs (~483 Mb) on 152 contigs. Within the assembled genome we identified and annotated 20,157 protein coding genes and assigned ~90% of them to orthogroups.
Paradise fish (Macropodus opercularis) is an air-breathing freshwater fish species with a signature labyrinth organ capable of extracting oxygen from the air that helps these fish to survive in hypoxic environments. The appearance of this evolutionary innovation in anabantoids resulted in a rewired circulatory system, but also in the emergence of species-specific behaviors, such as territorial display, courtship and parental care in the case of the paradise fish. Early zoologists were intrigued by the structure and function of the labyrinth apparatus and a series of detailed descriptive histological studies at the beginning of the 20th century revealed the ontogenesis and function of this specialized system. A few decades later, these fish became the subject of numerous ethological studies, and detailed ethograms of their behavior were constructed. These latter studies also demonstrated a strong genetic component underlying their behavior, but due to lack of adequate molecular tools, the fine genetic dissection of the behavior was not possible at the time. The technological breakthroughs that transformed developmental biology and behavioral genetics in the past decades, however, give us now a unique opportunity to revisit these old questions. Building on the classic descriptive studies, the new methodologies will allow us to follow the development of the labyrinth apparatus at a cellular resolution, reveal the genes involved in this process and also the genetic architecture behind the complex behaviors that we can observe in this species. K E Y W O R D S behavioral genetics, evo-devo, paradise fish

Lab head

Máté Varga
Department
  • Department of Genetics
About Máté Varga
  • The main focus of my group is the modelling of different rare, monogenic human diseases using zebrafish. We are especially interested in diseases linked to pseudouridylation defects and diseases resulting from the dysfunction of RecQ helicase orthologs. Lately we are also exploring how paradise fish could be turned into a model organism for evodevo and behavioral genetics studies.

Members (4)

Erika Fodor
  • Eötvös Loránd University
Renata Hamar
  • Eötvös Loránd University
Dávid Czimer
  • Eötvös Loránd University
Nóra Szabó
  • Eötvös Loránd University
Zsombor Varga
Zsombor Varga
  • Not confirmed yet
Latifa Kazzazy
Latifa Kazzazy
  • Not confirmed yet

Alumni (13)

Áron Zsigmond
  • Eötvös Loránd University
Bernadett Bosze
  • University of California, Davis
Kitti Dora Csalyi
  • Max Perutz Labs
Nora Papai
Nora Papai