Research Group on Systems Biology and Biotechnology in Microalgae

We combine omics technologies, computational modelling and mathematical methods to better understand microalgae and promote their biotechnological applications.

Human world population is increasing drastically generating unprecedented needs for energy and food. The massive exploitation of fossil fuels to satisfy this energy demand is producing a high accumulation of CO2 in the atmosphere and the subsequent climate change. This is affecting crop yield and reducing land area suitable for agriculture, ultimately, increasing malnutrition and its associated human diseases. In the current climate emergency scenario with energy and food shortage, microalgae cultivation represents an opportunity as promising sources of sustainable biofuels, agricultural biostimulants, animal feed and human nutrients contributing to the removal of the accumulating CO2. Nonetheless, the molecular mechanisms controlling the biosynthesis of compounds of biotechnological interest remain mostly uncharacterized in microalgae, hindering development of their full potential as cell-factories that could contribute substantially to solve these challenges. In our group we follow molecular systems biology multidisciplinary approaches combining omics technologies with High Performance Computing and mathematical methods to develop predictive models characterizing the molecular mechanisms controlling the functioning and physiology of microalgae to promote their biotechnological applications. We follow an evolutionary methodology in the characterization of these mechanisms extending our studies to the green lineage or viridiplantae focusing specifically in the terrestralization event during plant evolution. Our favourite model organisms are Ostreococcus tauri, Chlamydomonas reinhardtii, Klebsormidium nitens, Marchantia polymorpha and Arabidopsis thaliana. We also study the microalgae of industrial interest Haematococcus lacustris and Chromocloris zofingiensis and crops such as wheat or Triticum aestivium and tomato or Solanum lycopersicum.
Our group in part of the Institute for Plant Biochemistry and Photosynthesis (IBVF) in Seville (Spain) a join center between the University of Seville and Consejo Superior de Investigaciones Científicas (CSIC).

Our photochemostat installations

Our research group is multidisciplinary constituted by molecular biologists, biochemists, computer and data scientists. We are NOT organised into a pyramidal or hierarchical structure. We are just at different stages in our research careers and lifes with different responsabilities, duties and roles within our group. Our goal is to produce a nurturing and stimulating environment in our group in which we all have fun, learn, discover and grow as scientists and people. We all are strongly committed to open, fair and ethical science.

Below you can find a list of the papers published by members of our group in the last years:

• Martínez-Pérez A, de la Mata R, Romero-Campero FJ, Gómez R, Calonje M, Romero JM, Ruiz MT, Valverde F, Picó FX. (2026) Locally adapted Arabidopsis thaliana accessions show transcriptomic plasticity in a multi-timescale analysis of whole-genome gene expression in a natural environment. Plant Biology. doi: 10.1111/plb.70204


• Morales-Pineda M, García-González M, García-Gómez ME, Romero-Campero FJ, Ramos-González M. (2026) Acute Combination of Nitrogen Deprivation and High Irradiance Induces the Simultaneous Accumulation of Astaxanthin and Lutein in Continuous Cultures of the Microalga Chromochloris zofingiensis. Plants 15(6):902. doi: 10.3390/plants15060902


• Ramos-González M, Ramos-González V, Serrano-Pérez E, Arvanitidou C, Hernández-García J, García-González M, Romero-Campero FJ. (2026) PharaohFUN: phylogenomic analysis for plant protein history and function elucidation. Molecular Biology and Evolution 43(2):msag011. doi: 10.1093/molbev/msag011

• Romero-Losada AB, Arvanitidou C, García-Gómez ME, Morales-Pineda M, Castro-Pérez MJ, Chew YP, Van Ooijen G, García-González M, Romero-Campero FJ. (2025) Multiomics integration unveils photoperiodic plasticity in the molecular rhythms of marine phytoplankton. Plant Cell 37(2):koaf033. doi: 10.1093/plcell/koaf033


• Bedera-García R, García-Gómez ME, Personat JM, Couso I. (2025) Inositol polyphosphates regulate resilient mechanisms in the green alga Chlamydomonas reinhardtii to adapt to extreme nutrient conditions. Physiologia Plantarum 177(1):e70089. doi: 10.1111/ppl.70089

• Arvanitidou C, Ramos-González M, Romero-Losada AB, García-Gómez ME, García-González M, Romero-Campero FJ. (2024) Transcriptomic characterization of the response to a microalgae extract in Arabidopsis thaliana and Solanum lycopersicum. Journal of the Science of Food and Agriculture. doi: 10.1002/jsfa.13422


• de Los Reyes P, Serrano-Bueno G, Romero-Campero FJ, Gao H, Romero JM, Valverde F. (2024) CONSTANS alters the circadian clock in Arabidopsis thaliana. Molecular Plant 17(8):1204-1220. doi: 10.1016/j.molp.2024.06.006


• Liu C, Mentzelopoulou A, Hatzianestis IH, Tzagkarakis E, Skaltsogiannis V, Ma X, Michalopoulou VA, Romero-Campero FJ, Romero-Losada AB, Sarris PF, Marhavy P, Bölter B, Kanterakis A, Gutierrez-Beltran E, Moschou PN. (2024) A proxitome-RNA-capture approach reveals that processing bodies repress co-regulated hub genes. Plant Cell 36:559-584. doi: 10.1093/plcell/koad288


• van Es SW, Muñoz-Gasca A, Romero-Campero FJ, González-Grandío E, de Los Reyes P, Tarancón C, van Dijk ADJ, van Esse W, Pascual-García A, Angenent GC, Immink RGH, Cubas P. (2024) CO2 Levels Modulate Carbon Utilization, A gene regulatory network critical for axillary bud dormancy directly controlled by Arabidopsis BRANCHED1. New Phytologist 241:1193-1209. doi: 10.1111/nph.19420

• Yin X, Romero-Campero FJ, Yang M, Baile F, Cao Y, Shu J, Luo L, Wang D, Sun S, Yan P, Gong Z, Mo X, Qin G, Calonje M, Zhou Y.(2023) Binding by the Polycomb complex component BMI1 and H2A monoubiquitination shape local and long-range interactions in the Arabidopsis genome. Plant Cell 35:2484-2503. doi: 10.1093/plcell/koad112


• Morales-Pineda M, García-Gómez ME, Bedera-García R, García-González M, Couso I. (2023) CO2 Levels Modulate Carbon Utilization, Energy Levels and Inositol Polyphosphate Profile in Chlorella. Plants 12:129. doi: 10.3390/plants12010129

• Serrano-Pérez E, Romero-Losada AB, Morales-Pineda M, García-Gómez ME, Couso I, García-González M, Romero-Campero FJ. (2022) Transcriptomic and Metabolomic Response to High Light in the Charophyte Alga Klebsormidium nitens. Frontiers in Plant Science 13:855243. doi: 10.3389/fpls.2022.855243


• Romero-Losada AB, Arvanitidou C, de Los Reyes P, García-González M, Romero-Campero FJ. (2022) ALGAEFUN with MARACAS, microALGAE FUNctional enrichment tool for MicroAlgae RnA-seq and Chip-seq AnalysiS. BMC Bioinformatics 23(1):113. doi: 10.1186/s12859-022-04639-5


• Fernández-Rodríguez MJ, de la Lama-Calvente D, García-González M, Moreno-Fernández J, Jiménez-Rodríguez A, Borja R, Rincón-Llorente B. (2022) Integral Valorization of Two-Phase Olive Mill Solid Waste (OMSW) and Related Washing Waters by Anaerobic Co-digestion of OMSW and the Microalga Raphidocelis subcapitata Cultivated in These Effluents . Journal of Agricultural and Food Chemistry.70(10):3219-3227. doi: 10.1021/acs.jafc.1c08100

2021

• Couso I, Smythers AL, Ford MM, Umen JG, Crespo JL, Hicks LM. (2021) Inositol polyphosphates and target of rapamycin kinase signalling govern photosystem II protein phosphorylation and photosynthetic function under light stress in Chlamydomonas . New Phytologist. 232(5):2011-2025. doi: 10.1111/nph.17741.


• Hoys C, Romero-Losada AB, Del Río E, Guerrero MG, Romero-Campero FJ, García-González M. (2021) Unveiling the underlying molecular basis of astaxanthin accumulation in Haematococcus through integrative metabolomic-transcriptomic analysis. Bioresource Technology. 332:125150. doi: 10.1016/j.biortech.2021.125150.


• Yin X, Romero-Campero FJ, de Los Reyes P, Yan P, Yang J, Tian G, Yang X, Mo X, Zhao S, Calonje M, Zhou Y. (2021) H2AK121ub in Arabidopsis associates with a less accessible chromatin state at transcriptional regulation hotspots. Nature Communications. 12(1):315. doi: 10.1038/s41467-020-20614-1.


• Ojeda V, Jiménez-López J, Romero-Campero FJ, Cejudo FJ, Pérez-Ruiz JM. (2021) A chloroplast redox relay adapts plastid metabolism to light and affects cytosolic protein quality control. Plant Physiology. 187(1):88-102. doi: 10.1093/plphys/kiab246.


• Santamaría-Gómez J, Rubio MÁ, López-Igual R, Romero-Losada AB, Delgado-Chaves FM, Bru-Martínez R, Romero-Campero FJ, Herrero A, Ibba M, Ochoa de Alda JAG, Luque I. (2021) Role of a cryptic tRNA gene operon in survival under translational stress. Nucleic Acids Research. 49(15):8757-8776. doi: 10.1093/nar/gkab661.


• Sánchez-Cabrera M, Jiménez-López FJ, Narbona E, Arista M, Ortiz PL, Romero-Campero FJ, Ramanauskas K, Igić B, Fuller AA, Whittall JB. (2021) Changes at a Critical Branchpoint in the Anthocyanin Biosynthetic Pathway Underlie the Blue to Orange Flower Color Transition in Lysimachia arvensis. Frontiers in Plant Science. 12:633979. doi: 10.3389/fpls.2021.633979.

2020

• Couso I, Pérez-Pérez ME, Ford MM, Martínez-Force E, Hicks LM, Umen JG, Crespo JL. (2020) Phosphorus Availability Regulates TORC1 Signaling via LST8 in Chlamydomonas. Plant Cell. 32(1):69-80. doi: 10.1105/tpc.19.00179.

2019

• Ruger-Herreros M, Parra-Rivero O, Pardo-Medina J, Romero-Campero FJ, Limón MC, Avalos J. (2019) Comparative transcriptomic analysis unveils interactions between the regulatory CarS protein and light response in Fusarium. BMC Genomics. 20(1):67. doi: 10.1186/s12864-019-5430-x.

2018

• Couso I, Pérez-Pérez ME, Martínez-Force E, Kim HS, He Y, Umen JG, Crespo JL. (2018) Autophagic flux is required for the synthesis of triacylglycerols and ribosomal protein turnover in Chlamydomonas. Journal of Experimental Botany. 69(6):1355-1367. doi: 10.1093/jxb/erx372.

2017

• Zhou Y, Romero-Campero FJ, Gómez-Zambrano Á, Turck F, Calonje M. (2017) H2A monoubiquitination in Arabidopsis thaliana is generally independent of LHP1 and PRC2 activity. Genome Biology. 18(1):69. doi: 10.1186/s13059-017-1197-z.


• Merini W, Romero-Campero FJ, Gomez-Zambrano A, Zhou Y, Turck F, Calonje M. (2017) The Arabidopsis Polycomb Repressive Complex 1 (PRC1) Components AtBMI1A, B, and C Impact Gene Networks throughout All Stages of Plant Development. Plant Physiology. 173(1):627-641. doi: 10.1104/pp.16.01259.


• de Los Reyes P, Romero-Campero FJ, Ruiz MT, Romero JM, Valverde F. (2017) Evolution of Daily Gene Co-expression Patterns from Algae to Plants. Frontiers in Plant Science. 8:1217. doi: 10.3389/fpls.2017.01217.


• Serrano-Bueno G, Romero-Campero FJ, Lucas-Reina E, Romero JM, Valverde F. (2017) Evolution of photoperiod sensing in plants and algae. Current Opinion in Plant Biology. 37:10-17. doi: 10.1016/j.pbi.2017.03.007.


• Briones-Moreno A, Hernández-García J, Vargas-Chávez C, Romero-Campero FJ, Romero JM, Valverde F, Blázquez MA. (2017) Evolutionary Analysis of DELLA-Associated Transcriptional Networks. Frontiers in Plant Science. 8:626. doi: 10.3389/fpls.2017.00626.

One of the main goals of our group is the development of software tools acting as enabling technologies to promote systems biology studies in microalgae biotechnology in particular and in the green lineage in general. Below you can find a list of the software tools developed in our group:

Below you can find a list of the recent research projects developed or in progress in our group. Projects are sorted based on their final year:

• Summary: Photosynthetic eukaryotes of the green lineage (Viridiplantae), comprising green algae and terrestrial plants, have been pivotal in Earth evolutionary history and remain vital for maintaining atmospheric oxygen levels, mitigating climate change through carbon sequestration and providing energy for the vast majority of ecosystems including crops and fuels essential for human civilization. Their remarkable plasticity in temperature response and acclimation, underpinned by complex gene regulatory mechanisms including transcription factors and epigenetic modifications, has been crucial to enable them to colonize and thrive in very diverse environments. These include marine phytoplankton experiencing relatively stable ocean temperatures, benthic algae in intertidal zones facing rapid temperature shifts caused by tides, algae inhabiting seasonal ponds that desiccate during summers and terrestrial plants enduring seasonal and diurnal extreme temperatures. Understanding the regulatory mechanisms underlying this adaptability is crucial for advancing molecular plant science and addressing global challenges such as climate change and food security. The 29th United Nations Climate Change Conference (COP29) highlighted the urgent need to mitigate CO₂ emissions and emphasized the critical role of photosynthetic CO2 assimilation. This project seeks to uncover the conserved and divergent gene expression regulatory mechanisms underlying temperature response and acclimation in the green lineage. Specifically, it focuses on transcription factors involved in circadian clock regulation and epigenetic marks linked to Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2), H2Aub and H3K27me3. The novelty of this research project lies in its multidisciplinary, integrative and evolutionary approach. We will employ automated cultivation systems to generate high-resolution multiomics and physiological datasets, enabling comprehensive analyses of temperature resilience mechanisms. Multiomics data analysis will be applied to construct weighted temporal and longitudinal transcriptional gene networks for the planktonic unicellular chlorophyte Ostreococcus tauri, and gene co-expression networks for the benthic intertidal multicellular chlorophyte Codium tomentosum. Multiomics data analysis will also be employed from an evolutionary perspective to characterize the role over gene regulation in temperature response and acclimation of the epigenetic marks associated with PRC1 (H2Aub) and PRC2 (H3K27me3). This will be achieved by comparing the dynamics of these marks during temperature response and acclimation in the chlorophyte and streptophyte algae, Ostreococcus tauri and Klebsormidium nitens, which possess H3K27me3 but lack H2Aub, with the streptophyte algae Mesotaenium endlicherianum and the terrestrial bryophyte Marchantia, which have both marks. By studying transcriptional regulatory mechanisms across the green lineage, this project will advance our understanding of how algae and plants respond and acclimate to temperature changes. The research is especially relevant given the global climate emergency, characterized by rising temperatures and frequent heatwaves, especially in regions like the Iberian Peninsula, facing these challenges inland and along its coasts.
• Funding Agency: Ministry of Science and Innovation
• Principal Investigators: Francisco J. Romero-Campero, Mercedes García-González
• Funding: 237.500,00€
• Dates: 01/09/2025 - 31/08/2028

• Summary: Mitigation of CO2 is one of the most important problems that governments are facing in the last decade. In fact, European Union is proposing a 40% reduction of its emissions by the end of 2030 in the latest Climate and Energy framework and it pretends to be climate-neutral by 2050 (https://ec.europa.eu/clima/policies/strategies). In this sense, biological CO2 capturing, photosynthesis and its molecular regulation is an ancient process that needs to be revisited in order to help in the reduction of this greenhouse gas. In green microalgae, fixed CO2 is normally redirected to two different fates, cell growth (proteins) and carbon storage, mainly in the form of lipids and carbohydrates (starch) (Melis, 2013). In this sense, the use of these microorganisms for the production of biofuels is a good alternative to land crops because it lacks the main ethical implications on food/feed market and land use (Zhu et al., 2022). Thus, the understanding of the intracellular regulation of CO2 capturing and partitioning in green cells is fundamental in order to optimize their use. The green alga Chlamydomonas reinhardtii has been a perfect model for these kinds of studies. Actually, it has been used to describe the interaction between TOR kinase and the pyro-phosphorylated derivates of inositol polyphosphates (PP-InsPs) that controls carbon uptake and its final destination within these photosynthetic cells (Couso et al., 2016). Until that time, the applicability of inositol polyphosphates (InsPs) in green organisms was limited to biofortification strategies in crop genetic engineering for enhanced mineral density in traits, as these molecules are potent chelating agents that impact de bioavailability of iron and zinc (Raboy, 2020; Wang et al., 2022). Based on our previous results, this project is designed under the prospective view of understanding and manipulating InsPs biosynthesis in microalgae in order to increase the applicability of these green cells in the biofuels and other high added value compounds production towards the global strategy of carbon reduction.
• Funding Agency: Ministry of Science and Innovation
• Principal Investigators: Inmaculada Couso-Liañez
• Funding: 141.000,00€
• Dates: 12/2026

• Summary: The cultivation of photophrophic organisms represents an opportunity in the current climate emergency situation contributing to the removal of part of the accumulating CO2 in the atmosphere and its transformation into plant biomass. Since the last century the use of microalgae has been proposed for this purpose, due to the biotechnological characteristics of its cultivation. However, few initiatives have reached industrial scale. Currently only few microalgae species are massively cultivated (Chlorella, Spirulina, Dunaliella and Haematococcus) for products with very high added value (nutritional supplements, b-carotene, astaxanthin and more recently biostimulants for plant growth). Among the limitations detected for the widespread implementation of these technologies is the low yield of microalgae outdoors cultivation due to fluctuations in light and temperature and contamination by predators. Initiatives are being promoted to cultivate microalgae indoors, with artificial light, to reduce the aforementioned inconveniences. This project aims to analyse the effects of light regimes on microalgae cultures, studying in depth the transcription factors, identified in the previous project (MINOTAUR), which control the expression of key genes in the biosynthetic pathways of compounds of biotechnological interest (carotenoids, starch, phytohormones) in response to daily and seasonal light-dark cycles. For this study, the marine microalgae Ostrococcus tauri has been selected for its genomic and proteomic simplicity and its interesting biochemical composition. Our research will be also extended to other photosynthetic organisms considered the next links in the process of conquering dry land by plants, namely Klebsormidium nitens and Marchantia polymorpha. The main goal of our project consist in determining the level of conservation of the diurnal and seasonal rhythmic mechanisms controlling the biosynthesis of compounds of biotechnological interest. This will be achieved following a multidisciplinary approach combining cultivation of these photosynthetic organisms under controlled conditions with omic technologies , integrative multivariate analysis of massive data and network theory. Ultimately, our project seeks to construct the transcriptional network controlling diurnal and seasonal rhythms and characterize its evolution in the green lineage history. The midterm application of our results will represent an important progress in microalgae biotechnology, plant evolutionary biology and environmental sustainability.
• Funding Agency: Ministry of Science and Innovation
• Principal Investigators: Francisco J. Romero-Campero, Mercedes García-González
• Funding: 96.800,00€
• Dates: 01/2023 - 12/2025

• Summary: The cultivation of photophrophic organisms represents an opportunity in the current climate emergency, contributing to the removal of a fraction of the CO2 that is accumulating in the atmosphere by transforming it into plant biomass. Since the last century, microalgae cultivation, due to their biotechnological advantages, have been proposed as a sustainable solution to this problem. Nonetheless, few initiatives have reached industrial scale. The potential of some microalgae for biofuel photoproduction is widely recognized, due to their fast growth rate and ability to accumulate high levels of triacylglycerols with low requirements for land and high quality water. In spite of the progress that have been achieved, microalgae application into biofuel production has not reached the expected development. The main underlying limitations preventing microalgae full development as cell factories include those related to the selection and improvement of suitable microalgae strains. Moreover, the complexity of the biological systems underlying microalgae physiology makes mandatory the application of omics analysis based on mathematical/computational techniques such as those successfully applied in BigData projects. The adequacy and preeminence of the microalgae Raphidocelis subcapitata for the generation of biodiesel precursor fatty acids over other oleaginous microalgae has recently been demonstrated by our group. Under moderate nitrogen limitation R. subcapitata increases fatty acid content and modifies their profile, altering the relationship between unsaturated and saturated fatty acids. This constitutes an ideal lipid profile for the production of biodiesel. R. subcapitata potential in bioremediation has also been demonstrated in several applications. Specifically, our group has successfully used the nutrients contained in olive processing waste residues as a growth media for this microalgae. In this way, contributing to the decontamination of these discharges. The biomass thus obtained has been successfully tested as a raw material for biogas production. Multi-omics analysis based on mathematical/computational techniques has also been recently applied by our research group for the identification of transcription factors controlling the biosynthesis of the highly valuable carotenoid astaxanthin in the microalgae of industrial interest Haematococcus. All this supports the use of R. subcapitata as an excellent natural biological resource and the application of multi-omics techniques in order to contribute to a circular economy. In order to contribute to the full development of R. subcapitata as a cell factory, in this project, we aim at the identification of the transcriptional regulators controlling fatty acid metabolic pathways involved in the redistribution of carbon fixed by photosynthesis. The identified transcription factors and their target DNA sequecnes would constitute candidates for genetic system engineering for the optimazition of R. subcapitata as a biodiesel precursor fatty acids cell factory. This would contribute to improve the production of suitable fatty acids for the generation of carbon-neutral biofuels progressing towards the stabilization of greenhouse gas concentrations in the atmosphere, mainly CO2. This is a multidisciplinary project, where experiences in, molecular biology and microalgae biotechnology are combined with those of bioinformatics, which guarantee an effective symbiosis to achieve the proposed objetives.
• Funding Agency: Ministry of Science and Innovation
• Principal Investigators: Mercedes García-González, Francisco J. Romero-Campero
• Funding: 126.500,00€
• Dates: 01/2023 - 12/2024

• Summary:
• Funding Agency: Ministry of Science and Innovation
• Principal Investigators: Inmaculada Couso
• Funding:
• Dates: 01/2023 - 12/2024

• Summary: The aim of this project is to highlight the essential role of agricultural biostimulants, in particular those made from microalgae biomass. It seeks to demonstrate the effectiveness of these innovative solutions derived from microalgae to efficiently fight the effects of climate change on crops such as tomatoe and wheat. MicroClimatt will evaluate the physiological and transcriptomic effects induced by treatment with novel microalgae biostimulants on these crops, including conditions that are directly or indirectly caused by climate change, such as water stress or poor fertilisation rates. This project also aims to quantify the incorporation of carbon in the plant biomass of crops linked to increased productivity, to evaluate the increase of organic carbon incorporation in the soil sink and to study the improvement of soil fertility by treatment of crops with microalgae derivatives, as well as the improvement of soil quality, functionality and sustainability.
• Funding Agency: Ministry of Agriculture, Fisheries and Food.
• Principal Investigators: Francisco J. Romero-Campero, Mercedes García-González
• Funding: 96.497,71€
• Dates: 03/2021 - 03/2023