Center for Genomic Regulation (CRG)

The CRG is an International biomedical research institute of excellence created in December 2000. It is a non-profit foundation funded by the Catalan Government through the departments of Economy & Knowledge and Health, the Spanish Ministry of Economy and Competitiveness, and includes the participation of Universitat Pompeu Fabra (UPF).

The mission of the CRG is to discover and advance knowledge for the benefit of society, public health and economic prosperity.

The CRG believes that the medicine of the future depends on the groundbreaking science of today. This requires an interdisciplinary scientific team focused on understanding the complexity of life from the genome and the cell up to an entire organism and its interaction with the environment, offering an integrated view of genetic diseases.

URI permanent per a aquesta comunitat http://hdl.handle.net/10230/20545

Enviaments recents

The evolution of facultative symbiosis in stony corals
(Nature Research, 2025) Levy, Shani; Grau Bové, Xavier; Kim, Iana V.; Najle, Sebastián R.; Ksiezopolska, Ewa; Elek, Anamaria; Montes-Espuña, Laia; Montgomery, Sean A.; Mass, Tali; Sebé-Pedrós, Arnau
Most stony corals are obligate symbionts that are dependent on nutrients provided by the photosynthetic activity of dinoflagellates residing within specialized cells1. Disruption of this symbiotic consortium leads to coral bleaching and, ultimately, mortality2. However, a few coral species exhibit facultative symbiosis, allowing them to survive extended periods of bleaching3,4. Despite this resilience, the underlying biological mechanisms remain poorly understood. Here we investigate the genomic and cellular basis of facultative symbiosis in Oculina patagonica, a thermotolerant Mediterranean coral5,6. We sequenced and annotated a chromosome-scale genome of O. patagonica and built cell atlases for this species and two obligate symbiotic corals. Comparative genomic analysis revealed karyotypic and syntenic conservation across all scleractinians, with species-specific gene expansions primarily driven by tandem duplications. Single-cell transcriptomic profiling of symbiotic and naturally aposymbiotic wild specimens identified an increase in phagocytic immune cells and a metabolic shift in gastrodermal gene expression from growth-related functions to quiescent, epithelial-like states. Cross-species comparison of host cells uncovered Oculina-specific metabolic and signalling adaptations indicative of an opportunistic, dual-feeding strategy that decouples survival from symbiotic state.
Neurodevelopmental disorders: 2024 update
(University of Münster, 2024) Martínez de Lagrán Cabredo, María; Bascón-Cardozo, Karen; Dierssen, Mara
Neurodevelopmental disorders encompass a range of conditions such as intellectual disability, autism spectrum disorder, rare genetic disorders and developmental and epileptic encephalopathies, all manifesting during childhood. Over 1,500 genes involved in various signaling pathways, including numerous transcriptional regulators, spliceosome elements, chromatin-modifying complexes and de novo variants have been recognized for their substantial role in these disorders. Along with new machine learning tools applied to neuroimaging, these discoveries facilitate genetic diagnoses, providing critical insights into neuropathological mechanisms and aiding in prognosis, and precision medicine. Also, new findings underscore the importance of understanding genetic contributions beyond protein-coding genes and emphasize the role of RNA and non-coding DNA molecules but also new players, such as transposable elements, whose dysregulation generates gene function disruption, epigenetic alteration, and genomic instability. Finally, recent developments in analyzing neuroimaging now offer the possibility of characterizing neuronal cytoarchitecture in vivo, presenting a viable alternative to traditional post-mortem studies. With a recently launched digital atlas of human fetal brain development, these new approaches will allow answering complex biological questions about fetal origins of cognitive function in childhood. In this review, we present ten fascinating topics where major progress has been made in the last year.
Methods for identifying epilepsy surgery targets using invasive EEG: a systematic review
(MDPI, 2024) Ivankovic, Karla; Principe, Alessandro; Zucca, Riccardo; Dierssen, Mara; Rocamora Zúñiga, Rodrigo Alberto
Background: The pre-surgical evaluation for drug-resistant epilepsy achieves seizure freedom in only 50-60% of patients. Efforts to identify quantitative intracranial EEG (qEEG) biomarkers of epileptogenicity are needed. This review summarizes and evaluates the design of qEEG studies, discusses barriers to biomarker adoption, and proposes refinements of qEEG study protocols. Methods: We included exploratory and prediction prognostic studies from MEDLINE and Scopus published between 2017 and 2023 that investigated qEEG markers for identifying the epileptogenic network as the surgical target. Cohort parameters, ground truth references, and analytical approaches were extracted. Results: Out of 1789 search results, 128 studies were included. The study designs were highly heterogeneous. Half of the studies included a non-consecutive cohort, with sample sizes ranging from 2 to 166 patients (median of 16). The most common minimum follow-up was one year, and the seizure onset zone was the most common ground truth. Prediction studies were heterogeneous in their analytical approaches, and only 25 studies validated the marker through post-surgical outcome prediction. Outcome prediction performance decreased in larger cohorts. Conversely, longer follow-up periods correlated with higher prediction accuracy, and connectivity-based approaches yielded better predictions. The data and code were available in only 9% of studies. Conclusions: To enhance the validation qEEG markers, we propose standardizing study designs to resemble clinical trials. This includes using a consecutive cohort with long-term follow-up, validating against surgical resection as ground truth, and evaluating markers through post-surgical outcome prediction. These considerations would improve the reliability and clinical adoption of qEEG markers.
A multimodal lifestyle intervention complemented with epigallocatechin gallate to prevent cognitive decline in APOE- ɛ4 carriers with Subjective Cognitive Decline: a randomized, double-blinded clinical trial (PENSA study)
(Elsevier, 2025) Forcano, Laura; Soldevila-Domenech, Natalia; Boronat Rigol, Anna, 1990-; Sánchez Benavides, Gonzalo; Puig-Pijoan, Albert; Lorenzo, Thais; Aldea-Perona, Ana; Suárez-Calvet, Marc; Cuenca Royo, Aida Ma, 1981-; Gispert López, Juan Domingo; Gomis González, Maria, 1988-; Minguillón, Carolina; Diaz-Pellicer, Patricia; Piera, Iris; Langohr, Klaus; Dierssen, Mara; Pizarro Lozano, Mª Nieves; Mur-Gimeno E.; Grau-Rivera, Oriol; Molinuevo, José Luis; Torre Fornell, Rafael de la; PENSA working group
Background: The potential of dietary compounds to enhance the effects of multimodal lifestyle interventions (MLIs) on cognition in individuals at high risk of cognitive impairment remains unclear. Objectives: To assess whether the addition of a green tea extract enriched with epigallocatechin-3-gallate (EGCG) enhances the effects of an MLI. Design: Double-blind, randomized, two-arm, and placebo-controlled trial. Exploratory comparisons were made with a non-randomized group (NRG) receiving healthy lifestyle recommendations. Setting: Population-based study conducted in Barcelona, Spain PARTICIPANTS: APOE-ɛ4 carriers aged 60-80 with subjective cognitive decline INTERVENTION: A 12-month intensive MLI including dietary counseling, guided physical activity, and cognitive stimulation, combined with EGCG (5-6 mg/kg) or placebo, followed by a 3-month washout. Measurements: Primary endpoint was change in the modified Preclinical Alzheimer Cognitive Composite (PACC-exe) score. Results: 129 participants (65.1% 84 women, aged 66.7±5.5 years) were enrolled (52 MLI+EGCG, 52 MLI+placebo and 25 NRG), with126 (97.7%) included in the modified intention-to-treat analysis. After 12 months, no statistically significant difference was observed between MLI+EGCG and MLI+placebo in the PACC-exe (adjusted mean difference [AMD]: 0.12; 95%CI: -0.01, 0.24; p=0.061). However, participants in the MLI+EGCG group were 2.6 times more likely to show a reliable cognitive improvement. In exploratory analyses following a 3-month washout, the MLI+EGCG group showed significant cognitive benefits compared to the MLI+placebo (AMD: 0.19; 95%CI: 0.06, 0.32; p=0.005). Exploratory comparisons with the NRG also suggested greater gains in cognition and dementia risk reduction in both MLI groups, particularly with EGCG. Conclusions: While the primary outcome was not met, this proof-of-concept trial suggests that combining MLIs with EGCG warrants further investigation in larger, confirmatory studies.
Emergence of activation or repression in transcriptional control under a fixed molecular context
(National Academy of Sciences, 2025) Martinez-Corral, Rosa; Friedrich, Dhana; Frömel, Robert; Velten, Lars; Gunawardena, Jeremy; DePace, Angela H.
Transcription factors (TFs) can be both activators and repressors of gene transcription. This can manifest as "duality," where the transcriptional response increases (activation) with TF concentration in one context but decreases (repression) in another context, or as "nonmonotonicity," where, in the same context, the response increases in part of the concentration range and decreases outside that range. Here we use biophysical models of gene regulation to investigate how duality and nonmonotonicity relate to the interactions between a TF, Polymerase and the regulatory DNA. We distinguish two modes of TF action on Polymerase: "coherent," with interactions either positive or negative, and "incoherent," where interactions are a mix of both. For TFs that act incoherently from a single TF-DNA binding site, nonmonotonicity can arise, but only under nonequilibrium models. For single-site models, we show that nonmonotonicity can never happen under the common thermodynamic models of gene regulation, which consider equilibrium conditions and ignore the dissipative nature of the transcription process. Moreover, we show that merely changing the TF-DNA binding affinity, while keeping other features fixed, can tune the response between activation and repression, with responses either evaluated as a function of TF concentration or site number. Using the mammalian Sp1 as a case study and synthetically designed target sequences, we find experimental evidence for nonmonotonicity, and activation or repression tuned by affinity, which we interpret as evidence of incoherent action. Our work highlights the importance of moving from a TF-centric view to a systems view when reasoning about transcriptional control.

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Enviaments recents