Unlocking the secrets of life through systems thinking

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Our Vision

The I2SysBio is a joint Center of the University of València and the Spanish Research Council (CSIC). Our vision is to advance our understanding of life and its complexity through a systems biology approach, and to transfer this knowledge to make important contributions to science and society to improve human, animal, and environmental health.

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Our Methods

Our research actions revolve around the notion of ‘One health’, integrating different approaches aimed at balancing and optimising the health of people, animals and ecosystems in a sustainable manner. These actions are transversal among our Research Programs and are characterised by the implementation of a characterise, predict, design and apply workflow.
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Our Programs:

Systems Biotechnology

Gain a better understanding of the mechanisms underlying biological processes, and use this knowledge to develop new technologies and applications in fields such as biotechnology, medicine, and agriculture.

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Our Programs:

Pathogen Systems Biology

Better understand the mechanisms by which pathogens cause disease and develop strategies for treating and preventing infectious diseases.

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Our Programs:

Theoretical and Computational Systems Biology

Develop methods and computational approaches to analyse biological processes, and to use this knowledge to predict the behaviour of biological systems and design new interventions or treatments.

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Annual Report 2021 - 2023

A walk through the years

2021
2022
2023

A Walk Through Year 2021

February 2021FUNDING
April 2021FUNDING
April 2021INSTITUTIONAL
May 2021INSTITUTIONAL
June 2021INSTITUTIONAL
September 2021AWARDS
November 2021INSTITUTIONAL
December 2021OUTREACH
December 2021INSTITUTIONAL
December 2021AWARDS
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A Walk Through Year 2022

February 2022INSTITUTIONAL
February 2022OUTREACH
April 2022OUTREACH
May 2022OUTREACH
July 2022INSTITUTIONAL
September 2022FUNDING
September 2022AWARD
June 2022FUNDING
September 2022FUNDING
October 2022FUNDING
December 2022FUNDING
December 2022INSTITUTIONAL
December 2022AWARD
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A Walk Through Year 2023

January 2023FUNDING
January 2023OUTREACH
February 2023AWARD
March 2023INSTITUTIONAL
March 2023INSTITUTIONAL
May 2023INSTITUTIONAL
May 2023OUTREACH
May 2023METHODS
June 2023AWARD
June 2023AWARD
June 2023OUTREACH
June 2023AWARD
July 2023FUNDING
June 2023AWARD
August 2023OUTREACH
December 2023FUNDING
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Scientific Highlights

2021
2022
2023
Computational Synthetic Biology
Non-Coding RNA Networks
Viral Biology
Evolutionary Systems Virology
Molecular Epidemiology

Computational Synthetic Biology

Systems Biotechnology

Modelling of synthetic metabolic pathways

Description:

  • Societal demand for sustainable biomolecules urges efficient biomanufacturing solutions.
  • Automation is essential to establish metabolic engineering as a biomanufacturing technology.•
  • Automated retro-biosynthetic and optimal experimental design approaches are highlighted.
  • Advances and needs towards full automation of the metabolic engineering DBTL pipeline are discussed.

Article:

Automated engineering of synthetic metabolic pathways for efficient biomanufacturing I Otero-Muras*, P Carbonell*. Metabolic Engineering 63, 61-80

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Non-Coding RNA Networks

Systems Biotechnology

Circular RNAs acting as potential protein-coding transcripts in plants

Description:

Circular RNAs (circRNAs) are widely expressed transcripts found in multiple species including Archaea, plants, yeast, and most metazoans. Endogenous circRNAs were first found in humans associated with the non-canonical splicing of cancer-related transcripts. Today it is established that circRNAs constitute a novel class of regulatory non-coding RNAs, potentially involved in the modulation of gene expression in both animal and plant cells. However recent studies have provided strong experimental evidence that circRNAs can also act as non-canonical translatable transcripts in animal cells supporting the emerging paradigm that the true coding-potential of circRNAs may have been underestimated and that animal circRNAs may exert more biological functions than previously predicted. In this work, we used two viroids (pathogenic exogenous circRNAs) as experimental tools to explore the coding potential of circRNAs in plants. Our results revealed that the analyzed ex-circRNAs contain putative ORFs able to encode peptides carrying specific subcellular localization signals. Bioassays in well-established hosts revealed that mutations in these ORFs diminish the biological efficiency of these pathogenic ex-circRNAs. Finally, ex-circRNAs were found linked with polysomes, evidencing their physical interaction with the translational machinery of the plant cell. In short, these results provide novel insights supporting that viroid RNA might be translated in functional peptides potentially playing an essential role in their life cycle, and therefore challenge the previous dogma of pathogenic ncRNAs.

Article:

Might exogenous circular RNAs act as protein-coding transcripts in plants?. 2021. Marquez, Navarro, Seco, Pallas, Gomez*. RNA Biol. 14:1-10.

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Viral Biology

Pathogen Systems Biology

Defining the tolerance of viral capsids to mutations illuminates key features of their function and evolution.

Description:

The capsids of non-enveloped viruses are highly multimeric and multifunctional protein assemblies that play key roles in viral biology and pathogenesis. They encode the information to correctly assemble without aggregation and package the genome, are sufficiently stable to protect the genome during transit from cell to cell and host to host yet readily disassemble upon recognizing their receptor, and are capable of escaping the immune system. In this work, we generated viral populations harboring nearly all possible amino acid mutations and assessed how they affect the ability of the virus to spread. With this information, we were able to understand the capacity of viral capsids to evolve and better understand the structural plasticity of key structural and functional features of the viral capsid.

Article:

Globally defining the effects of mutations in a picornavirus capsid. 2021. Mattenberger, Latorre, Tirosh, Stern, Geller*. eLife 10:e64256.

Defining the tolerance of viral capsids to mutations illuminates key features of their function and evolution.
Defining the tolerance of viral capsids to mutations illuminates key features of their function and evolution.
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Evolutionary Systems Virology

Pathogen Systems Biology

Viruses can evolve to benefit the host organism

Description:

Viruses are seen as selfish pathogens that harm their hosts to ensure their own survival. However, metagenomic studies are drawing a new picture in which viruses are present everywhere and not always associated with diseases. A classic observation in plant pathology is that the outcome of infection depends on environmental conditions. Here, using experimental evolution, we show that the relationship between a plant virus and its natural host can evolve from pathogenic to mutualistic under severe drought conditions. While viral strains evolved in normal watering conditions increased their virulence, drought-evolved viral strains confer plants with greater resistance to drought. We show that this transition to mutualism depends on a complex reorganization of hormone-induced signaling pathways and changes in gene expression.

Article:

Plant virus evolution under strong drought conditions results in a transition from parasitism to mutualism. 2021. González, Butković, Escaray, Martínez-Latorre, Melero, Pèrez-Parets, Gómez-Cadenas, Carrasco, Elena*. Proc. Natl. Acad. Sci. USA 118: e2020990118.

Evolutionary Systems Virology
Experimental evolution design. TuMV was either serially passed in standard watering conditions or in severe drought conditions. Three independent evolution experiments were performed. At the end of evolution, the performance of all the evolved viral lineages was evaluated in plants maintained in standard conditions and in drought.
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Molecular Epidemiology

Pathogen Systems Biology

Genomic analysis of the entry and initial spread of SARS-CoV-2 in Spain

Description:

The COVID-19 pandemic represented a major societal challenge to which our group helped to respond through coordinating a consortium of over 70 groups (SeqCOVID), mainly clinical but also from basic science labs and public health administrations, which established one of the most successful genomic epidemiology studies at a national level. Thanks to a very early response – we were the first group to obtain genome sequences of the virus, we were able to analyze in great detail the initial entry and early spread of the virus in Spain. These analyses revealed a surprising difference in composition of the initial lineages arriving in Spain compared to other European countries. This was likely related to the important role of a few introductions followed by large “superspreading” events of lineage 19A in our country. Our analyses also revealed a constant influx of new lineages, mainly from Italy, the Netherlands, and the United Kingdom which contributed to an increasing diversity of the virus despite the reduction in the number of new infections as a result of the lockdown measures.

Article:

The first wave of the COVID-19 epidemic in Spain was associated with early introductions and fast spread of a dominating genetic variant. 2021. López, Chiner-Oms, García de Viedma ,…, Coscolla*, González-Candelas* and Comas*. Nat Genet 53, 1405–1414. doi.org/10.1038/s41588-021-00936-6

Genomic analysis of the entry and initial spread of SARS-CoV-2 in Spain
Genomic analysis of the entry and initial spread of SARS-CoV-2 in Spain
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Biosystems Design
Virus Experimental Evolution
Evolutionary Systems Virology
Genomics of gene expression
Modeling of Biological Systems

Biosystems Design

Systems Biotechnology

Understanding stochastic gene expression using synthetic biology principles

Description:

Gene expression is inherently stochastic and pervasively regulated. While substantial work combining theory and experiments has been carried out to study how noise propagates through transcriptional regulations, the stochastic behavior of genes regulated at the level of translation is poorly understood. Here, a synthetic genetic system in which a target gene is down-regulated by a protein translation factor, which in turn is regulated transcriptionally, was engineered. The phage MS2 coat protein was exploited to regulate the expression of a green fluorescent protein at the level of translation. This synthetic system was instrumental to gain fundamental knowledge on stochasticity and regulation at an overlooked level within the genetic information flow. By monitoring both the expression of the regulator and the regulated gene at the single-cell level, the stochasticity of the system was quantified. The analysis allows to capture the cell-to-cell variability in genes regulated both transcriptionally and translationally.

Article:

Gene regulation by a protein translation factor at the single-cell level. 2022. Dolcemascolo, Goiriz, Montagud-Martinez, Rodrigo*. PLoS Comput. Biol. 18: e1010087.

Systems-Biotechnology
Regulation with a protein translation factor. a) Schematics of the gene regulatory system implemented in a bacterial cell. IPTG is the external molecule that controls the expression of the protein translation factor (eBFP2-MS2CP). sfGFP is the final output of the system. b) Histograms of single-cell fluorescence for eBFP2 (fused to the regulatory protein) for different induction conditions with IPTG. On top, sequence details of the cis-regulatory region (DNA level) for transcriptional regulation (PLlac promoter). c) Histograms of single-cell fluorescence for sfGFP (the regulated protein) for different induction conditions with IPTG. On top, sequence details of the cis-regulatory region (RNA level) for post-transcriptional regulation (MS2CP RNA motif).
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Virus Experimental Evolution

Pathogen Systems Biology

Enveloped viruses show increased propensity to cross-species transmission and zoonosis.

Description:

The transmission of viruses between different host species is a major source of emerging diseases and is of particular concern in the case of zoonotic transmission from mammals to humans. Several zoonosis risk factors have been identified, but it is currently unclear which viral traits primarily determine this process, as previous work has focused on a few hundred viruses that are not representative of actual viral diversity. Here we investigate fundamental virological traits that influence cross-species transmissibility and zoonotic propensity by interrogating a database of over 12,000 mammalian virus-host associations. Our analysis reveals that enveloped viruses tend to infect more host species and are more likely be zoonotic than non-enveloped viruses, while other viral traits such as genome composition, structure, size or the viral replication compartment play less obvious role. This contrasts with the previous notion that viral envelopes did not significantly impact or even reduced zoonotic risk, and should help better prioritize outbreak prevention efforts. We suggest several mechanisms by which viral envelopes could promote cross-species transmissibility, including structural flexibility of receptor-binding proteins and evasion of viral entry barriers.

Article:

Enveloped viruses show increased propensity to cross-species transmission and zoonosis. Valero-Rello, Sanjuán*. 2022. Proc. Natl. Acad. Sci. USA 119: e2215600119.

Enveloped viruses show increased propensity to cross-species transmission and zoonosis
The average number of host species per virus increases more rapidly with the cutoff N for enveloped viruses than for nonenveloped viruses. Dot sizes are proportional to the number of different viruses included in each cutoff. The dots are shown for N ≥ 2, N ≥ 3, and so on. Dots for N ≥ 1 were too large for visualization and are omitted.
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Evolutionary Systems Virology

Pathogen Systems Biology

The immune system as a whole conditions the evolution of virus

Description:

Host-pathogen interactions create ongoing battles where both sides continuously evolve to outcompete the other. We aimed to understand this evolutionary arms race by studying how the innate immune system affects viral diversity and evolution. Our model involved the fruit fly, Drosophila melanogaster, and its natural virus, Cripavirus drosophilae (Drosophila C virus; DCV). To do this, we used eight different fly genotypes, each lacking certain immune pathways responsible for detecting and fighting infections. We infected both normal and mutant flies with DCV and then passed the virus through ten rounds of reinfection in new flies. We analyzed the viral population after each round using advanced sequencing techniques and evaluated the infection severity at the beginning and end of the experiment. Our findings showed that flies missing any of the immune pathways had a higher viral genetic diversity but less severe infections. Overall, our research suggests that the innate immune system as a whole plays a crucial role in limiting viral diversity and evolution, rather than specific antiviral defenses acting alone.

Article:

Innate immune pathways act synergistically to constrain RNA virus evolution in Drosophila melanogaster. 2022. Mongelli, Lequime, Kousathanas, Gausson, Blanc, Nigg, Quintana-Murci, Elena*, Saleh. Nat. Ecol. Evol. 6: 565-578.

Evolutionary-Systems-Virology
In the DCV evolution experiment, female flies injected with DCV were used to contaminate cages, and groups of 500 or immune-deficient males and females were cycled over 10 passages. The DCV genome consists of single-stranded positive-sense RNA with two ORFs: ORF 1 encodes non-structural proteins involved in viral replication, including a silencing suppressor, RNA helicase, and RNA-dependent RNA polymerase; ORF 2 encodes structural proteins VP1 to VP4 that form the viral capsid.
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Genomics of Gene Expression

Theoretical and Computational Systems Biology

Software development for detecting alternative expression programs and isoform networks in single cells

Description:

Single-cell transcriptome (scRNA-seq) analysis is a powerful tool for characterizing transcriptional programs associated with specific cell types. scRNA-seq has been instrumental in understanding tumor progression, tissue cell-type composition, and development. However, current scRNA-seq technologies have limitations in detecting alternative expression programs at the single-cell level. Alternative expression is a mechanism of functional diversity that is critical for cell type identity. In this work, we developed Arcode, a software package for unveiling isoform networks in single cells. We introduced a novel correlation metric adapted to single-cell data and combined long and short-read sequencing. We demonstrated that isoforms exhibit primarily cell-type-specific expression and that isoform-level networks operate to delineate the cellular functional content defining neural cell types.

Article:

Acorde unravels functionally interpretable networks of isoform co-usage from single cell data. 2022. Arzalluz-Luque, Salguero, Tarazona, Conesa*. Nat Commun 13(1):1828.

Software development for detecting alternative expression programs and isoform networks in single cells
Acorde analysis workflow. Acorde combines long and short read transcriptome sequencing at the single-cell level and introduces a new correlation metrics, percentile correlation to cluster isoforms by their expression patterns. Assignment of alternative isoforms to clusters are used to infer cell-type specific differential isoform usage and create isoform expression networks. A proprietary software for isoform functional annotation helps to interpret the analysis results in terms of cell-type specific functions regulated by isoform expression.
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Biophysical Modeling of Cell Packing

Theoretical and Computational Systems Biology

Biophysical modeling of cell packing

Description:

This paper identifies a quantitative law that governs the formation and connectivity of epithelial cells in curved tissues through the shape known as scutoids. The researchers propose an energy-based stochastic model that predicts how cells minimize energy to adopt scutoid shapes, facilitating efficient packing and mechanical stability in curved structures. This model quantitatively explains the increase in scutoid formation with reduced cell adhesion, which lowers the energy barrier for new cellular connections. This finding provides a quantitative framework for understanding the biophysical principles of tissue organization​.

Article:

A quantitative biophysical principle to explain the 3D cellular connectivity in curved epithelia. 2022. Gómez-Gálvez, Vicente-Munuera, Anbari, Tagua, Gordillo-Vázquez, A. Andrés-San Román, Franco-Barranco, Palacios, Velasco, Capitán-Agudo, Grima, Annese, Arganda-Carreras, Robles, Márquez, Buceta *, Escudero*. Cell Systems 13: 8, 631-643.e8.

Scutoids are prismatic-like geometric solids bound between two surfaces
Schematic representation of geometrical, topological, and biophysical concepts related to epithelial tissues. Scutoids are prismatic-like geometric solids bound between two surfaces. (B) A T1-transition is a tissue rearrangement observed in epithelial surfaces where a 4-cell motif swaps nearest neighbors along time. An apico-basal transition is similar to the T1-transition but instead of developing along the time, it develops along space. A 2D tessellation (aka a 2D mosaic) is a partition of a surface with tiles that do not overlap or leave any gaps. (E) A 2D Voronoi diagram is a particular type of tessellation built by convex polygons (Voronoi cells). (F) The surface tension energy is related to the cell-cell adherence through their lateral area contacts.
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Biosystems Design
Metabolic regulatory networks
Viral Biology
Microbial Single-Cell Genomics
Evolutionary Systems Virology

Biosystems Design

Systems Biotechnology

Challenging the molecular clock hypothesis

Description:

The molecular clock hypothesis, which dates back to early times of molecular biology, states that the rates at which genes accumulate mutations are constant with time. Neutral theory of molecular evolution predicts, in addition, that such clocks are Poissonian stochastic processes (i.e., evolution seen as a Brownian motion with diffusivity such that mean and variance are equal). Despite the results from seminal studies of some viral genes are in tune, the molecular clock hypothesis still raises controversy, as evolution appears as a highly volatile and vagary stochastic process due to environmental changes, transmission bottlenecks, and recombination and speciation events. Indeed, such a null model can be rejected in numerous cases, and overdispersed populations in genetic variation (i.e., with larger variance than mean) seem common across phyla. In this work, we exploited the unprecedented monitoring of the evolution of a human virus (SARS-CoV-2) in nature to conduct a study aimed at describing this process as a (non-)Brownian motion, considering the number of acquired mutations as the displacement of the viral particle from the origin. For that, several biostatistical analyses over millions of whole genome sequences at the ensemble level were evaluated on the basis of a time-dependent probabilistic mathematical model, without relying on phylogeny. Of note, our results challenge the conventional molecular clock hypothesis by providing new theoretical foundations for viral evolution.

Article:

A variant-dependent molecular clock with anomalous diffusion models SARS-CoV-2 evolution in humans. 2023. Goiriz, Ruiz, Garibo-i-Orts, Conejero, Rodrigo*. Proc. Natl. Acad. Sci. USA 120: e2303578120.

Understanding-stochastic-gene-expression-using-synthetic-biology-principles-min
Characterization of SARS-CoV-2 evolution in UK. A) Schematics of the evolutionary motion of the virus (viewed as a stochastic process). Inset: associated state-transition diagram. B) 2D projection of all viral sequences colored by date.
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Metabolic Regulatory Networks

Systems Biotechnology

Plant Transcription factors driving light and UV responses in fruits

Description:

What are the causes and effects of berry color variegation? Does a central genetic switch contribute to the abundance of phenylpropanoids and isoprenoids in variegated berries? Can we integrate computational analyses and experimental evidence to disentangle these questions? Pigmented and unpigmented sections of rare, variegated grapevine berries, were compared by Zhang et al. using transcriptomics, cistromics and untargeted metabolomics.

White variegation in red-skinned grapevine fruits is caused by the presence of non-functional alleles of MYBA1/A2 transcription factors that naturally control anthocyanin biosynthesis. The absence of these pigments enhances a ripening-dependent regulatory network mediated by MYB24 that promotes protection against ultraviolet and high light intensity stress. In response, white skin sections accumulate higher levels of antioxidant monoterpenes and UV-shielding flavonols; however, these compounds only partially ameliorate the detrimental effects of excessive radiation. Genes related to carotenoid metabolism, photosynthesis, and other light signaling responses are bound and directly regulated by MYB24. in silico and in vitro analyses were used to demonstrate that MYB24 orchestrates different specialized metabolism pathways in berry skins in response to increased levels of radiation caused by pigment depletion.

Article:

MYB24 orchestrates terpene and flavonol metabolism as light responses to anthocyanin depletion in variegated grape berries. 2023. Zhang, Ferrier, Orduña, Santiago, Peris, Wong, Kappel, Savoi, Loyola, Amato, Kozak, Miaomiao Li, Liang, Carrasco, Meyer-Regueiro, Espinoza, Hilbert, Figueroa-Balderas, Cantu, Arroyo-Garcia, Arce-Johnson, Claudel, Errandonea, Rodríguez-Concepción, Duchêne, Huang, Castellarin, Tornielli, Barrieu*, Matus*. The Plant Cell 35, 12, 4238–4265.

Responses to anthocyanin depletion in variegated grape berries
Berry variegation is a rare chimerism event in grapevine (Vitis vinifera L.). This cover art illustrates the variety of berry variegation phenotypes that can be observed at ripening in the cultivar ‘Béquignol Noir’.
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Viral Biology

Pathogen Systems Biology

Uncovering how viral capsids are targeted by human neutralizing antibodies and how the virus can escape them

Description:

Non-enveloped viruses constitute 40% of all mammalian viruses and are an important cause of disease in humans. Neutralizing antibodies play a key role in resolving viral infections and confer protection against reinfection. To successfully infect and spread, viruses must overcome neutralizing antibodies by mutating their target, which is the viral capsid. It is unknown how neutralizing antibodies present in blood attack viral capsids. 

In this work, we have introduced a large number of mutations in the capsid, the protein shell of the virus that encloses its genetic material and tracked their frequency with high resolution. The result shows for the first time how polyclonal sera (antibodies circulating in the blood) target the virus and how it can escape neutralization. Specifically, it shows that the response of these antibodies in immunized laboratory mice is directed to a single region of the viral capsid, while the sera generated by the humans present varied responses that are directed to one or several different regions. Additionally, the authors have generated a panel of viruses harboring mutations that escape neutralization and used them to define which regions of the viral capsid are targeted in a large sample of sera, uncovering unexpected conservation in human responses. Finally, the work shows that escaping neutralization requires multiple mutations, but comes at a cost to viral fitness.

Article:

Comprehensive profiling of neutralizing polyclonal sera targeting 
coxsackievirus B3. 2023. Álvarez-Rodríguez, BUCETA*, & GELLER*. /Nat Commun/ 14, 6417. 

www.uv.es_viralbiology
Image showing neutralizing antibodies targeting a non-enveloped viral capsid.
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Microbial Single-Cell Genomics

Systems Biotechnology

Newly discovered symbiotic bacteria provide chemical protection for their nudibranch host

Description:

Nudibranchs are marine, soft-bodied mollusks known for using natural products as a defense against predators. While some animals rely on symbiotic microbes for the production of chemical defense molecules, the origin of these compounds in nudibranchs has remained unclear. Džunková et al. employed a fluorescent probe to label the biosynthesis of secondary metabolites in vivo, allowing them to capture bacterial symbionts actively producing these compounds in the mantle of the nudibranch Doriopsilla fulva, even if the microbes cannot be cultured in the laboratory. They discovered a new bacterial symbiont, Candidatus Doriopsillibacter californiensis, belonging to the Ca. Tethybacterales order – a previously uncultured lineage of sponge symbionts not found in nudibranchs before. This symbiont is a core component of the skin microbiome of D. fulva and is almost absent from its internal organs. Crude extracts of D. fulva contained secondary metabolites consistent with a beta-lactone encoded in the Ca. D. californiensis genome. Beta-lactones are an underexplored class of secondary metabolites with significant pharmaceutical potential, previously unreported in nudibranchs. This study highlights how probe-based, targeted single-cell sorting approaches can lead to the discovery of novel bacterial symbionts and their in vivo-produced secondary metabolites.

Article:

Synthase-selected sorting approach identifies a beta-lactone synthase in a nudibranch symbiotic bacterium. 2023. Džunková*, La Clair, Tyml, Doud, Schulz, Piquer-Esteban, Porcel Sanchis, Osborn, Robinson, Louie, Bowen, Bowers, Lee, Arnau, Díaz-Villanueva, Stepanauskas, Gosliner, Date, Northen, Cheng, Burkart, Woyke. Microbiome. 11(1):130.

Microbial Single-Cell Genomics
a) Molecular structure of the probe KC-12 used for fluorescent labeling of biosynthetic activity in vivo, alongside its negative control variant. b) Flow cytometry bi-plots of skin cell suspensions from the nudibranch Doriopsilla fulva incubated with the KC-12 probe and the negative control probe. c) Fluorescent microscopy images of nudibranch skin tissues, showing that cells labeled with the KC-12 probe (purple) overlap with microbial cells labeled with probes specific for the symbiotic bacterium Candidatus Doriopsillibacter californiensis (red).
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Evolutionary Systems Virology

Pathogen Systems Biology

Genome rearrangements result in resistance to virus

Description:

This manuscript presents important findings that inform the genetic underpinnings of the model plant Arabidopsis’ resistance to Potyvirus rapae (turnip mosaic virus; TuMV). The strength of the evidence in the manuscript is exceptional, with very large sample sizes, careful controls, multiple follow-up experiments, and broadening to the evolutionary context. The evidence provides robust support for each of the manuscript’s conclusions and could pave the way for functional studies.

Article:

Genetic basis of Arabidopsis thaliana response to infection with naïve and adapted isolates of turnip mosaic virus. 2023. Butković, Ellis, González, Jaegle, Nordborg, Elena*. eLife 12: RP89749.

Evolutionary Systems Virology
Results of the genome-wide association analysis of symptoms severity and necrosis of Arabidopsis plants inoculated with TuMV. In red loci in chromosome 2 that show a strong association with the disease phenotypes.
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The periods in numbers

Staff 2023

Administrative
0

Women

Men

6

3

Technical support
0

Women

Men

6

4

Researchers (PI)
0

Women

Men

8

18

Young PI
0

Women

Men

2

3

Postdocs
0

Women

Men

16

14

PhD students
0

Women

Men

23

32

Total Members
0

Training 2021 - 2023

PhD Theses
0
Master Theses
0
Undergraduate Theses
0
Total students
0

Scientific Production

Scientific papers 2021
0
Scientific papers 2022
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Scientific papers 2023
0

Competitive and private funding 2021-2023

2021
2022
2023

I2SYSBIO BUDGET 2021

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I2SYSBIO PROJECTS 2021

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I2SYSBIO BUDGET 2022

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I2SYSBIO PROJECTS 2022

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RESEARCH BUDGET 2023

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Mapping of Collaborations by Research Groups

Signed Spinoffs 2021-2023

Patents 2021 - 2023

Priority patent applications
0
International PCT applications
0
License contracts
0

C2-thioether tryptophan trimers and tetramers and use thereof

Description:

Tryptophan trimers and tetramers for use in the treatment and/or prevention of betacoronavirus infection, particularly SARS-CoV-2. These new betacoronavirus antivirals are useful for inhibiting virus entry through inhibition of the interaction of viral Spike (S) proteins with the cellular host cell receptor(s).

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Gut microbiota composition for use in the prevention and/or treatment of a mental disorder with memory impairment in a subject

Description:

Gut microbiota comprising a wide range of species range of species with a wide variety of applications applications for use in the prevention and/or specific specific treatment of a mental disorder with memory impairment in a subject.

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Tri-substituted tetrahydrofurans and use thereof

Description:

New tri-substituted tetrahydrofurans and their use as antivirals for coronavirus infections. The inventors have discovered tri-substituted tetrahydrofurans, which are active compounds against coronaviruses in vitro, specifically of the species TGEV, MHV, HCoV-OC43 y SARS-CoV-2. These new compounds that they have synthesized could give rise to a new family of antivirals and can be useful in the treatment of coronavirus infections, specifically of SARS-CoV-2.

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In vitro method for diagnosis of Pneumocystis jirovecii infection

Description:

Research staff from the Fundació per al Foment de la Investigació Sanitària i Biomèdica de la Comunitat Valencia (FISABIO), the University of Valencia, the Andalusian Health Service, the University of Chile and the Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV, Mexico) have developed a new in vitro method for the diagnosis of Pneumocystis jirovecii infection. Their work aims to improve detection by developing a single-round PCR quantification assay based on the amplification of the Msg-A multicopy gene family, that is more cost efficient, faster (1 hour) and decreases the chances of contamination. On the other hand, this method also allows the quantification of the pathogen and has greater sensitivity.

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Nasal spray with antiviral activity

Description:

Novel polysaccharides that are effective in treatment and prevention of viral infections. These compounds are mimics of heparan sulfates present in cells. They act as decoy trap preventing the virus from adhering to epithelial cells, thus slowing down the process of infection. Nontoxic. A wide variety of respiratory viruses such as RSV, SARS-CoV2, common cold or Influenza could be treated.

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Improvement of resveratrol and oxyresveratrol production in Morus for cosmetic, pharmaceutical and nutraceutical industries

Description:

More efficient, one-step method for obtaining resveratrol and oxyresveratrol. Stilbenoids are biologically active phenolic compounds with a broad spectrum of antibiotic and pharmacological activity. They have been shown to have beneficial effects on human health such as the treatment of atherosclerosis, anti-inflammatory or antioxidant effect, anti-cancer, among others. It is therefore important to have an adequate source of stilbenes for use as food supplements or drug adjuvants. Among these compounds are resveratrol and oxyresveratrol, with important beneficial effects demonstrated in medical and cosmetic experiments.

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Method for accurate and simultaneous detection of multiple viruses in samples

Description:

This novel technique, based on CRISPR-Cas9 approaches, allows to detect multiple different DNA sequences with a high degree of specificity, and can be easily associated to other biochemical reactions in order to deliver a tailored signal that can be used for a differentiated diagnosis. Furthermore, simultaneity can be achieved by avoiding Cas9 catalytic reactions. The technology has been tested successfully with multiple SARS-CoV-2 genetic regions and different coronaviruses simultaneously, resulting in an accurate detection and distinction of each target. It can also be adapted to further viruses.

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Wine yeast strains with optimized properties and their method of production

Description:

Researchers at the Institute for Integrative Systems Biology have described a new method for obtaining yeast strains with improved wine-making properties. The yeast strains thus obtained have been validated in a tasting of the organoleptic properties of the wine produced with them.

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