A walk through 2024
Collaborative Networks for Innovation: I²SysBio’s Active Role in the CSIC BCB and AMR Connections
The Spanish National Research Council (CSIC) has launched a series of Scientific-Technical Collaboration Networks, known as Connections, to promote interdisciplinary research on emerging and high-impact topics. The Computational Biology and Bioinformatics (BCB) Connection, coordinated by Dr. Ana V. Conesa (I²SysBio) and Dr. Pablo Chacón (IQF), brings together extensive institutional expertise in the field. Over 20 I²SysBio researchers from seven groups are actively involved. The Institute also contributes to the Antimicrobial Resistance Connection, strengthening collaboration in this crucial area.
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Dr. Pilar Domingo-Calap Receives National Recognition for Innovative Antibacterial Research
As part of the 60th Anniversary edition of the Farmaindustria Young Researchers Award, the Evaluation Committee granted the main prize to Cristina Mayor-Ruiz and awarded four accésits, one of which was presented to I²SysBio researcher Dr. Pilar Domingo-Calap.
Her research, focused on the use of bacteriophages as biomedical tools against antibiotic-resistant bacteria, was particularly commended for its translational impact and strong outreach profile.
On April 16, the I2SysBio Senate unanimously endorsed the management proposal submitted by Gustavo Gómez as Director and Rosario Gil as Vice Director. This endorsement was ratified by the Institute’s Board, which subsequently forwarded the proposal to the Presidency of the CSIC and the Rectorate of the University of Valencia. On May 25, the new Directorate was formally appointed by the respective institutions, succeeding the previous leadership team of Emilia Matallana and Santiago F. Elena.
I²SysBio Earns ASPIRA-MaX Recognition in CSIC’s Strategic Excellence Initiative
As part of the first phase of the MaX-CSIC strategic program, the Institute for Integrative Systems Biology (I²SysBio, a joint UV–CSIC center) submitted a self-assessment that was reviewed by two independent evaluators. This phase of the program recognizes the efforts of CSIC research centers in their pursuit of excellence, with a total of 40 institutes receiving this distinction.
The award includes an allocation of €20,000 to support the development of a scientific project proposal and an associated excellence plan.
I²SysBio Participates in Longstanding Educational Exchange Program with Iowa State University
For the past fifteen years, the Faculty of Biological Sciences at the University of Valencia has maintained an academic agreement with Iowa State University (ISU), enabling ISU biology students to undertake month-long research stays in its laboratories.
In 2024, six ISU students engaged in collaborative research with various groups, including Elianies Segarra, who joined the Systems metabolic engineering group at I²SysBio, under the supervision of Alba Arévalo.
In 2024, Alfred Fillol, Arnau Montagud, and Guillem Salazar joined the faculty of the Institute for Integrative Systems Biology (I²SysBio) as a CDEIGENT Researcher, a CSIC Senior Scientist, and a Ramón y Cajal Researcher, respectively.
Tribute to Dr. Emilia Matallana through the Dones de Ciència mural in Sagunto
A mural honoring renowned Spanish biochemist and University of Valencia professor Emilia Matallana has been unveiled at IES 5 in her hometown of Sagunto as part of the Dones de Ciència project, which celebrates leading women in science. Created by artist Alba Moncho, the artwork features Matallana’s portrait surrounded by symbols of her research on wine yeast.
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Advancing Synthetic Biology: ERC Project Led by Dr. Otero-Muras Receives €2M Funding
Irene Otero-Muras, CSIC Senior Scientist at the Institute for Integrative Systems Biology (I²SysBio, CSIC–Universitat de València), will lead a Consolidator ERC project aimed at developing novel methodologies in synthetic biology. The project seeks to enable the programming of cognitive functionalities in microorganisms, with potential applications in bioremediation and human health. Endowed with a budget of two million euros, the project will span five years.
Scientific Highlights
Description
A team from I2SysBio develop a new computer tool to investigate the complexity of the genome.
The computer program allows for the quality control, filtering and annotation of transcripts. The software has been published in Nature Methods and allows to analyze data obtained by long-read sequencing of the transcriptome. This system makes it possible to discover new RNA molecules and understand their structures. This deepens the knowledge of the diversity of the transcriptome in all aspects of life, from the formation of the organism to its diseases.
Pardo-Palacios, F. J., Arzalluz-Luque, A., Kondratova, L., et al. (2024). SQANTI3: Curation of long-read transcriptomes for accurate
identification of known and novel isoforms. /Nature Methods, 21/,
793–797. https://doi.org/10.1038/s41592-024-02229-2
Description
Immune digital twins for complex human pathologies: applications, limitations, and challenges.
Digital twins represent a key technology for the future of biomedicine. These computational models represent the health state of individual patients over time, enabling optimal therapeutics and forecasting patient prognosis. In this review we outline the progress and initiatives on immune digital twins to facilitate communication between interdisciplinary communities, its application in drug discovery and the challenges to make immune digital twins a reality.
Niarakis, A., Laubenbacher, R., An, G., et al. (2024). Immune digital twins for complex human pathologies: Applications, limitations, and challenges. /npj Systems Biology and Applications, 10/, 141. https://doi.org/10.1038/s41540-024-00
Description:
Evolutionary trends of alternative splicing.
Alternative splicing is the post-transcriptional mechanism by which many different isoforms are generated from a single gene, contributing to increasing spatio-temporal transcriptome complexity. I2SysBio researchers propose a novel genome-level measure of alternative splicing, which associates it with a single value for each species. Thus, a comparative analysis of species spanning the whole tree of life has revealed certain evolutionary trends in alternative splicing, prevalence in specific lineages, and relation to genome compositional structures.
de la Fuente, R., Díaz-Villanueva, W., & Arnau, V. (2024). Evolutionary trends of alternative splicing. /eLife, 13/, RP94802. https://doi.org/10.7554/eLife.94802.1
TheSiMBioSys: Theoretical and In Silico Modeling of Biological Systems
Description
Stochastic analysis of Ebola infection in small zoonotic niches.
This study shows that stochastic fluctuations can either eliminate or sustain filovirus infections in small bat colonies, influencing disease dynamics and control strategies. Stochastic effects in small fruit bat colonies reveal critical insights into how zoonotic viruses like Ebola persist or fade, depending on population size.
Mursel, S., Bocchini, P., & Buceta, J. (2024). Stochastic analysis of Ebola infection in small zoonotic niches. /Royal Society Open Science, 11/(11). https://doi.org/10.1098/rsos.240298
Description
Álvarez-Rodríguez, B., Velandia-Álvarez, S., Toft, C., & Geller, R. (2024). Mapping mutational fitness effects across the coxsackievirus B3 proteome reveals distinct profiles of mutation tolerability. /PLOS Biology, 22/(7), e3002709. https://doi.org/10.1371/journal.pbio.3002709
Description
A multispecies study reveals the diversity and potential regulatory role of long noncoding RNAs in cucurbits.
In this study, the ncRNA-lab has generated the first comprehensive catalog of the different types of lncRNAs in the family Cucurbitaceae, describing prediction-confidence, molecular features, and conservation rate.
Plant long noncoding RNAs (lncRNAs) exhibit features such as tissue-specific expression, spatiotemporal regulation, and stress responsiveness. In this work has been analyzed more than 1000 available transcriptomic studies performed in nine representative species to generate a comprehensive inventory of lncRNAs in cucurbits.
Villalba-Bermell, P., Marquez-Molins, J., & Gomez, G. (2024). A multispecies study reveals the diversity and potential regulatory role of long noncoding RNAs in cucurbits. /The Plant Journal, 120/(2), 799–817. https://doi.org/10.1111/tpj.17013
Description
Repurposing the mammalian RNA-binding protein Musashi-1 as an allosteric translation repressor in bacteria.
This study demonstrates the use of the mammalian Musashi-1 (MSI-1) RNA-binding protein as a tool for regulating gene expression in Escherichia coli. MSI-1 functions as an allosteric translational repressor that responds to fatty acids. We repurposed this eukaryotic gene expression regulatory mechanism, introducing a new orthogonal regulatory layer in prokaryotes for translation control.
Dolcemascolo, R., Heras-Hernandez, M., Goiriz, L., et al. (2024). Repurposing the mammalian RNA-binding protein Musashi-1 as an allosteric translation repressor in bacteria. /eLife, 12/, RP91777. https://doi.org/10.7554/eLife.91777
Description
Lejri, R., Mekki, A., Ellafi, A., et al. (2024). Genomic features of metal-resistant bacteria suitable for tannery effluent bioremediation. /Journal of Water Process Engineering, 68/, 106406. https://doi.org/10.1016/j.jwpe.2024.106406
Description
A kinetic finite volume discretization of the multidimensional PIDE model for gene regulatory networks.
In this study, a finite volume discretization scheme for partial integro-differential equations (PIDEs) describing the temporal evolution of protein distribution in gene regulatory networks is proposed. It is shown that the obtained set of ODEs can be formally represented as a compartmental kinetic system with a strongly connected reaction graph. This allows the application of the theory of nonnegative and compartmental systems for the qualitative analysis of the approximating dynamics.
Vághy, M. A., Otero-Muras, I., Pájaro, M., & Szederkényi, G. (2024). A kinetic finite volume discretization of the multidimensional PIDE model for gene regulatory networks. /Bulletin of Mathematical Biology, 86/(2), 22. https://doi.org/10.1007/s11538-023-01251-3
Description
Activation of the yeast Retrograde Response pathway by adaptive laboratory evolution with S-(2-aminoethyl)-L-cysteine reduces ethanol and increases glycerol during winemaking.
Global warming causes an increase in the levels of sugars in grapes and hence in ethanol after wine fermentation. Therefore, alcohol reduction is a major target in modern oenology. In this study, it has been shown that hyperactivation of the Retrograde Response pathway by ALE with AEC is a valid approach for generating ready-to-use, low-ethanol mutants with a desirable phenotype in winemaking.
Garrigós, V., Picazo, C., Matallana, E., & Aranda, A. (2024). Activation of the yeast retrograde response pathway by adaptive laboratory evolution with S-(2-aminoethyl)-L-cysteine reduces ethanol and increases glycerol during winemaking. /Microbial Cell Factories, 23/(1), 231. https://doi.org/10.1186/s12934-024-02504-z
Description
DetSpace: a web server for engineering detectable pathways for bio-based chemical production.
DetSpace web server provides a set of integrated tools that allows a user to select and design a biological circuit that performs the sensing of a molecule of interest by its enzymatic conversion to a detectable molecule through a transcription factor. In that way, the DetSpace web server allows synthetic biologists to easily design biosensing routes for the dynamic regulation of metabolic pathways in applications ranging from genetic circuits design, screening, production, and bioremediation of bio-based chemicals, to diagnostics and drug delivery.
Martín Lázaro, M., Marín Bautista, R., & Carbonell, P. (2024). DetSpace: A web server for engineering detectable pathways for bio-based chemical production. /Nucleic Acids Research/, W1–W5. https://doi.org/10.1093/nar/gkae287
Description
Domínguez-Santos, R., Baixeras, J., Moya, A., et al. (2024). Gut microbiota is not essential for survival and development in /Blattella germanica/, but affects uric acid storage. /Life, 14/, 153.
https://doi.org/10.3390/life14010153
Description
Vidal-Verdú, À., Torrent, D., Iglesias, A., et al. (2024). The highly differentiated gut of /Pachnoda marginata/ hosts sequential microbiomes: Microbial ecology and potential applications. /npj Biofilms and Microbiomes, 10/, 65. https://doi.org/10.1038/s41522-024-00531-7
Description
Genomic features of metal-resistant bacteria suitable for tannery effluent bioremediation.
This study demonstrates the potential of genomically characterized bacterial consortia for effective bioremediation of tannery wastewater under real effluent conditions. While many bacterial strains are being isolated for bioremediation purposes worldwide, the lack of genomic analyses is still hampering the proper understanding of the pathways involved in bioremediation and slowing the discovery rate of novel bioremediation mechanisms. The seven Enterococcus faecium strains and two Bacillus licheniformis strains isolated in the present study possess unique genomic features, including novel gene content unrelated to previously known bioremediation pathways, as revealed by metabolic reconstruction and pan-genome analysis.
Vidal-Verdú, À., Torrent, D., Iglesias, A., et al. (2024). The highly differentiated gut of /Pachnoda marginata/ hosts sequential microbiomes: Microbial ecology and potential applications. /npj Biofilms and Microbiomes, 10/, 65. https://doi.org/10.1038/s41522-024-00531-7
Description
T7 phage-assisted evolution of riboswitches using error-prone replication and dual selection.
A novel T7 phage-based system rapidly evolves RNA riboswitches by directly integrating them into the phage genome. This method employs a dual-selection strategy, using a host gene essential to T7 to positively select for functional “ON” states and a anti-T7 gene to negatively select against leaky “OFF” states. The result is an accelerated evolution process that efficiently isolates highly specific riboswitches with a broad functional range.
Description
The circadian and photoperiodic clock of the pea aphid.
Pea aphids change how they reproduce based on day length. In long days, they produce only live-born females. When days get shorter, they switch to making males and eggs to survive winter. This process is likely controlled by a weak internal clock linked to hormones in the brain.
Colizzi, F. S., Martínez-Torres, D., & Helfrich-Förster, C. (2024). The circadian and photoperiodic clock of the pea aphid. /Journal of Comparative Physiology A, 210/. https://doi.org/10.1007/s00359-023-01660-8
Description
Story of an infection: scientists describe the relationship between a virus and its host organism during its development.
Researchers at the Institute of Integrative Systems Biology (CSIC-UV) have described, with the highest temporal resolution so far, how the model organism Caenorhabditis elegans responds to chronic infection by the Orsay virus from birth to sexual maturity. Using a multidisciplinary approach, they tracked the virus’s spread and host gene expression over time, identifying early, correlated, and late genetic responses. This detailed view reveals how the host controls infection without eliminating the virus, offering a successful defense model. Their findings, published in Science Advances, could guide the search for new antiviral targets with clinical potential.
Castiglioni, V. G., Olmo-Uceda, M. J., Villena-Giménez, A., et al. (2024). Story of an infection: Viral dynamics and host responses in the /Caenorhabditis elegans–Orsay virus/ pathosystem. /Science Advances/. https://doi.org/10.1126/sciadv.adn5945
Description
Majander, K., Pla-Diaz, M., du Plessis, L., et al. (2024). Redefining the treponemal history through pre-Columbian genomes from Brazil. /Nature, 627/, 182–188.
https://doi.org/10.1038/s41586-023-06965-x
Description
Buigues, J., Viñals, A., Martínez-Recio, R., et al. (2024). Phylogenetic evidence supporting the nonenveloped nature of hepadnavirus ancestors. /Proceedings of the National Academy of Sciences, 121/(45). https://doi.org/10.1073/pnas.2415631121
Description
Álvarez-Rodríguez, B., Velandia-Álvarez, S., Toft, C., & Geller, R. (2024). Mapping mutational fitness effects across the coxsackievirus B3 proteome reveals distinct profiles of mutation tolerability. /PLOS Biology, 22/(7), e3002709. https://doi.org/10.1371/journal.pbio.3002709
Description
The University and the CSIC obtain the first clinical results of viruses that destroy multi-resistant bacteria.
This research, in collaboration with Yale and Spanish hospitals, studied the use of phages—viruses that attack bacteria—to treat respiratory infections, especially in cystic fibrosis patients with antibiotic-resistant bacteria. Two patients received phage therapy without side effects, though both developed antibodies against the phages. The study, published in Med, is the first to report immune responses after nebulized phage treatments, suggesting the need for personalized approaches and long-term monitoring. These promising findings support further clinical trials and advance the future of phage therapy.
Bernabeu-Gimeno, M., Pardo-Freire, M., Chan, B. K., et al. (2024). Neutralizing antibodies after nebulized phage therapy in cystic fibrosis patients. /Med, 5/, 1096.
https://doi.org/10.1016/j.medj.2024.05.017
Description
VIPERA, a software that evaluates how SARS-CoV-2 evolves throughout the infection.
A research team from I2SysBio and other Spanish institutions has developed VIPERA, an open-source software tool that tracks how SARS-CoV-2 evolves within chronically infected patients. Chronic cases can last for months and may give rise to more dangerous variants. VIPERA analyzes genetic changes across samples over time and produces automated, easy-to-read reports. In applying the tool to a real case, researchers uncovered key mutation patterns, including those linked to immune evasion and increased transmissibility—highlighting the software’s value in monitoring and understanding viral evolution.
Álvarez-Herrera, M., Sevilla, J., Ruiz-Rodriguez, P., et al. (2024). VIPERA: Viral intra-patient evolution reporting and analysis. /Virus Evolution, 10/(1). https://doi.org/10.1093/ve/veae018
The period in Numbers
Staff 2024
Women
Men
17
26
Women
Men
27
42
Women
Men
8
2
Women
Men
21
14
Women
Men
73
84
Training 2024
Commitment to Advanced Research Training at I²SysBio
Aligned with its institutional mission, I²SysBio remains dedicated to training researchers in a multidisciplinary environment with strong scientific and professional outlooks. In 2024, eight doctoral theses were successfully defended, and over one hundred students—including undergraduate, graduate, and participants in mobility programs such as Erasmus+—received training at the Institute.
This year also marked the launch of the PhD Excellence Program, enrolling 14 doctoral candidates (photo). The program is designed to complement PhD training with advanced courses and resources that foster excellence in research and academic development.
Funds Raised
Outreach and Scientific Culture
I²SysBio in the Media
In 2024, I²SysBio published 34 news on its institutional website, including 24 official press releases. These communications generated 349 mentions across mainstream media outlets, reflecting the Institute’s increasing visibility and commitment to public science communication.
Press Highlights
Scientific life at I²SysBio
In 2024, I²SysBio hosted 44 scientific seminars, including four focused on innovation, alongside four institutional events.
Researchers from I²SysBio actively contributed to the organization of conferences, colloquia, and debates, such as Darwin Day , the Matinal d’Evolució, and Biophyzza 2024.
Notably, the Institute promoted cross-cutting initiatives that reinforce its commitment to research integrity and science outreach. These included a workshop on scientific ethics—“Are We Losing the Battle Against the Growing Use of AI? Is There Gender Bias?”—as well as the event La Ciència a Través de l’art”.
Science Education
In 2024, I²SysBio actively participated in several science dissemination initiatives, including Mednight (The Mediterranean Researchers’ Night), Expociencia, and the Amgen Transferciencia Program.
Science Education
Parc Científic de la Universitat de València, C/ Catedrático Agustín Escardino 9, 46980 Paterna (Valencia), España.