GRIB https://grib.upf.edu/ Research programme on biomedical informatics Fri, 25 Sep 2026 09:06:33 +0000 en-US hourly 1 https://grib.upf.edu/wp-content/uploads/2024/02/cropped-grib-32x32.png GRIB https://grib.upf.edu/ 32 32 Mar Albà showcases GRIB research at leading international microprotein symposium https://grib.upf.edu/3-mar-alba-showcases-grib-research-at-leading-international-microprotein-symposium/ https://grib.upf.edu/3-mar-alba-showcases-grib-research-at-leading-international-microprotein-symposium/#respond Fri, 25 Sep 2026 09:05:32 +0000 https://grib.upf.edu/?p=2332 The meeting, focused on advancing knowledge of microproteins and their biomedical and biotechnological applications, brought together experts from around the world working across diverse areas of microprotein biology.

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Mar Albà, ICREA Research Professor and Co-director of the Biomedical Informatics Research Programme (GRIB), participated as a co-organizer and speaker at an international symposium dedicated to microprotein research, held in Umeå, Sweden, from 14 to 16 September 2026.

The meeting, focused on advancing knowledge of microproteins and their biomedical and biotechnological applications, brought together experts from around the world working across diverse areas of microprotein biology.

During the symposium, Albà, presented the latest research from her group on the evolution of microproteins using yeast as a model system. The work has recently been published as a preprint on bioRxiv and provides new insights into the evolutionary origins and diversification of this emerging class of proteins. The symposium served as a platform for sharing cutting-edge discoveries and fostering international collaborations in this rapidly evolving field.

The event, titled “Decoding Microproteins: From Basic Biology to Biotechnological Innovations”, highlighted recent advances in understanding microprotein function, evolution and applications, reinforcing the importance of interdisciplinary research efforts in this area.

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Dr. Qiuyan Chen Visits GRIB to Discuss New Insights into GPCR Signaling and Arrestin Activation https://grib.upf.edu/dr-qiuyan-chen-visits-grib-to-discuss-new-insights-into-gpcr-signaling-and-arrestin-activation/ https://grib.upf.edu/dr-qiuyan-chen-visits-grib-to-discuss-new-insights-into-gpcr-signaling-and-arrestin-activation/#respond Wed, 23 Sep 2026 08:31:07 +0000 https://grib.upf.edu/?p=2327 The Indiana University School of Medicine researcher presented her latest work on how phosphorylation patterns and membrane lipids cooperate to regulate arrestin activation and GPCR signaling.

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21/09/2026

On September 18, GRIB had the pleasure of hosting Dr. Qiuyan Chen, Assistant Professor at the Indiana University School of Medicine, for a guest seminar entitled “Decoding Arrestin Activation: Phosphopeptide Barcodes Meet Membrane Lipids.”

The seminar brought together researchers interested in cell signaling, structural biology, and drug discovery to explore recent advances in our understanding of the molecular mechanisms that regulate G protein-coupled receptor (GPCR) signaling, one of the most important pathways in cellular communication and a major target for therapeutic development.

During her presentation, Dr. Chen shared findings from her laboratory on the activation of arrestins, key proteins that control and redirect GPCR signaling. Her research demonstrates that arrestin activation is governed by the interplay between receptor phosphorylation patterns and the surrounding membrane lipid environment. By combining cryo-electron microscopy (cryo-EM) with innovative nanodisc systems, her team has revealed how distinct phosphorylation “barcodes” and membrane interactions generate different arrestin conformations and signaling outcomes.

These findings provide important insights into the structural principles underlying receptor regulation and help explain why different GPCRs engage arrestins in distinct ways. The work also highlights potential opportunities for the development of more selective therapeutic strategies targeting GPCR-mediated pathways.

Dr. Chen’s scientific career includes training at Vanderbilt University, the University of Michigan, and Purdue University, where she contributed to the determination of the first cryo-EM structure of a GPCR-kinase complex. Today, her laboratory combines structural and biophysical approaches, including cryo-EM, crystallography, electron paramagnetic resonance (EPR), and fluorescence-based techniques, to investigate the mechanisms governing receptor signaling and regulation.

The seminar stimulated lively discussion among attendees and offered a valuable opportunity to exchange ideas on the structural basis of GPCR function and the future directions of this rapidly evolving field.

GRIB would like to thank Dr. Chen for an engaging and insightful presentation, as well as all participants for contributing to a successful scientific event.

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Mireia Vallès-Colomer honoured with National Research Award https://grib.upf.edu/mireia-valles-colomer-honoured-with-national-research-award/ https://grib.upf.edu/mireia-valles-colomer-honoured-with-national-research-award/#respond Thu, 06 Aug 2026 07:52:42 +0000 https://grib.upf.edu/?p=2321 Mireia Vallès-Colomer has received the Margarita Salas Award for her research in biology

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UPFR PRESS

05/08/2026

On 30 July, Mireia Vallès-Colomer, researcher and member of the teaching staff at Pompeu Fabra UniversitY and leader of The Microbiome Research Group at GRIB, was presented with National Research Award from the Spanish Ministry of Science, Innovation and Universities. Vallès-Colomer received the Margarita Salas Award, which recognizes outstanding research in biology by researchers under the age of 40.

According to the Ministry, the award presented to Mireia Vallès-Colomer, director of the Microbiome Research Group in the Department of Medicine and Life Sciences (MELIS) and GRIB, acknowledges her “research linking the gut microbiome to mental health”. She also, remarked that the award has given her “a renewed burst of energy […]. Having our work recognized gives meaning to the immense amount of time and effort we devote to it and confirms that the seemingly risky decision to return home and continue conducting research at the highest level was indeed correct.”

The young researcher, who has led her research group in MELIS-UPF since 2023 after completing her education in Leuven (Belgium) and Trento (Italy), added: “It is an honour to receive an award that bears the name of a leading figure such as Margarita Salas. At the same time, the fact I am the first woman to receive it shows that there is still much progress to be made.”

About Mireia

Mireia Vallès-Colomer is a tenure-track lecturer and principal investigator at Pompeu Fabra University (UPF), where she heads the Microbiome Research Group in MELIS-UPF. With degrees in Microbiology and Computational Biology from Universitat Autònoma de Barcelona and Vrije Universiteit Brussel (Belgium), her research centres on the role of the human microbiome in mental health and the mechanisms underlying its transmission between individuals.

As a PhD student in the laboratory of Dr Raes at VIB–KU Leuven (Belgium), she led the first population-based study linking the composition and function of the gut microbiome to anxiety and depression. This research, published in Nature Microbiology (2019), systematically characterized the production and degradation of neuroactive compounds using metagenomic data and was singled out by Nature Milestones 2019 as a key contribution to human microbiome research. Later, as an EMBO postdoctoral researcher in the laboratory of Dr Segata at the University of Trento (Italy), she demonstrated the multigenerational transmission of the gut microbiome within families (Nature Microbiology, 2022) and led the first large-scale characterization of person-to-person transmission networks of oral and gut microbiomes (Nature, 2023), establishing a population-level framework to investigate the social transmission of microbes.

She currently leads a team of seven researchers focused on developing and applying computational and statistical methods to analyse the relationship between microbiome composition, social transmission dynamics and mental health. Her scientific output has amassed over 15,000 citations, and, in 2025, she was recognized by Clarivate as a Highly Cited Researcher, placing her in the top 1% of the most cited researchers worldwide.

 

You can read more about it here

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ORFeus, boosting research into the dark proteome https://grib.upf.edu/orfeus-boosting-research-into-the-dark-proteome/ https://grib.upf.edu/orfeus-boosting-research-into-the-dark-proteome/#respond Fri, 10 Jul 2026 08:19:39 +0000 https://grib.upf.edu/?p=2311 Hospital del Mar Research Institute is participating in this European project, which aims to advance knowledge of the functions of the proteins that make up the so-called dark proteome. Led by the Princess Máxima Center for Pediatric Oncology in the Netherlands, it will train fifteen PhD students, who will focus their research on this field.

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HMRIB PRESS

Hospital del Mar Research Institute is participating in this European project, which aims to advance knowledge of the functions of the proteins that make up the so-called dark proteome. Led by the Princess Máxima Center for Pediatric Oncology in the Netherlands, it will train fifteen PhD students, who will focus their research on this field.

The European ORFeus programme aims to boost research into the field of the dark proteome, a group of proteins whose existence was unknown until recently. It will do so by providing training to fifteen PhD students, who will focus their research on this field. Hospital del Mar Research Institute (HMRIB) is the only institution in Spain participating in the project, through the research group led by Dr Mar Albà, ICREA Research Professor and Director of the Biomedical Informatics Research Programme at HMRIB, which will host one of the researchers.

 

ORFeus

Cancer cell expressing microprotein (colored in red)

 

The dark proteome regulates processes in tumour cells and other diseases and may play an important role in the development of new treatments, such as immunotherapy. With fifteen PhD candidates dedicated to studying this previously unknown group of proteins, the project is expected to achieve an increasingly deeper understanding of this research field and its potential applications in new therapies.

The researchers will work in fifteen research groups across different European countries. In addition to their research activities, the PhD candidates will follow a joint training programme. They will receive both scientific and professional training and will undertake placements in participating companies. This will allow the most promising discoveries to be translated more rapidly into clinical practice. Collaboration is a central element of the programme.

The ORFeus programme will begin in October with the recruitment of students and will run for four years. It is coordinated by the Princess Máxima Center for Pediatric Oncology in the Netherlands and involves 26 international partners. ORFeus is funded by the European Union’s Horizon Europe research and innovation programme under the Marie Skłodowska-Curie Actions, grant agreement No. 101309891.

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Mar Albà to participate in the “Genome Dark Matter” mini-symposium celebrating the 25th anniversary of the Human Genome https://grib.upf.edu/mar-alba-to-participate-in-the-genome-dark-matter-mini-symposium-celebrating-the-25th-anniversary-of-the-human-genome/ https://grib.upf.edu/mar-alba-to-participate-in-the-genome-dark-matter-mini-symposium-celebrating-the-25th-anniversary-of-the-human-genome/#respond Wed, 10 Jun 2026 09:44:51 +0000 https://grib.upf.edu/?p=2303 Mar Albà participates in the mini-symposium Genome Dark Matter - celebrating the 25th anniversary of the human genome, which is to be celebrated at the University of Barcelona the 15th of June

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On 15 June, Mar Albà, Director of the evolutionary genomics group at the Hospital del Mar Research Institute and co-coordinator of the Research Programme on Biomedical Informatics (GRIB), will participate in the mini-symposium Genome Dark Matter, organized by the University of Barcelona as part of the events commemorating the 25th anniversary of the Human Genome.

Four researchers in the fields of genomics and bioinformatics will provide insights into this topic. The speakers will be:

Dr. Mar Albà; ICREA Research Professor, Hospital del Mar Research Institute (HMRI):
“The Dark Matter of Peptideins”

Dr. Tamara Perteghella; Centre for Genomic Regulation (CRG), Universitat Pompeu Fabra (UPF):
“ncRNAs, a Continuously Expanding Universe”

Dr. Josep Casacuberta; CSIC Research Professor, Centre for Research in Agricultural Genomics (CRAG):
“Centromeres and Repetitive Sequences: Filling the Gaps with Long-Read Sequencing”

Dr. Cristian Cañestro; University of Barcelona (UB), Biodiversity Research Institute (IRBio):
“Gene Loss and Gain: The Death and Birth of the Stars in the Genome’s Dark Matter”

The talks will be followed by a round-table discussion with the speakers, moderated by Dr. Josep F. Abril (UB/IBUB).

The event is open to the public and will take place in the Aula Magna of the Faculty of Biology at the University of Barcelona.

#25APGH

Event details

Mini-symposium: Genome Dark Matter
Date: 15 June
Venue: University of Barcelona
More information: https://web.ub.edu/ca/web/25-anys-genoma/w/minisimposi-25apgh-la-mat%C3%A8ria-fosca-del-genoma-

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A new study names part of the human genome https://grib.upf.edu/a-new-study-names-part-of-the-human-genome/ https://grib.upf.edu/a-new-study-names-part-of-the-human-genome/#respond Tue, 19 May 2026 09:03:11 +0000 https://grib.upf.edu/?p=2299 An international study published in the journal Nature has designated a subset of the so-called dark proteins - proteins with no known function - as peptideins. Characterising them opens the door to studying them and analysing their functions

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HMRIB PRESS

An international study published in the journal Nature has designated a subset of the so-called dark proteins – proteins with no known function – as peptideins. Characterising them opens the door to studying them and analysing their functions.

The TransCODE consortium, of which the Hospital del Mar Research Institute is the only research centre in Spain to be a member, has just published a new article that advances knowledge of the so-called dark genome, a part of the human genome that has not been studied and whose function is unknown. The journal Nature publishes the study, in which it designates thousands of previously unannotated proteins as peptideins.

Dr Mar Albà, ICREA professor and director of the Biomedical Informatics Research Programme (GRIB) at the Hospital del Mar Research Institute (HMRIB), is one of the authors of the study. She highlights the importance of analysing this part of the genome, noting that “some of these proteins may have important functions in the cell. In addition, even for those that are not functional, they are a reservoir of new proteins from an evolutionary point of view”.

The researchers started from a list of more than 7,000 DNA sequences suspected of coding for dark proteins. They have been studied and identified thanks to the development of specific techniques to sequence the RNA fragments protected by ribosomes, and have been validated by proteomics. These are proteins of recent origin from an evolutionary point of view, very small and with no known function. For all these reasons, they are not included in databases.

The new term, peptideins, is a combination of the words peptide, a short amino-acid fragment, and protein. Its creation allows them to be included in databases, thus facilitating possible new studies of their functions. In this regard, Dr Albà explains that “one line of research we want to pursue based on these results is to see which of them show patterns of phylogenetic conservation that indicate functionality. To do this, we plan to compare the dark proteomes of closely related species”. Some of these peptideins have been linked to diseases, such as childhood cancers, and to basic cellular functions.

 

 

Reference article

Deutsch, E.W., Kok, L.W., Mudge, J.M. et al. Expanding the human proteome with microproteins and peptideins. Nature (2026). https://doi.org/10.1038/s41586-026-10459-x

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A new pathway for developing cancer drugs discovered https://grib.upf.edu/a-new-pathway-for-developing-cancer-drugs-discovered/ https://grib.upf.edu/a-new-pathway-for-developing-cancer-drugs-discovered/#respond Tue, 19 May 2026 09:00:23 +0000 https://grib.upf.edu/?p=2294 An international research consortium, led by the University of Utah School of Medicine in Salt Lake City, United States, has discovered a new pathway that could enable the development of new cancer treatments.

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HMRIB PRESS
  • An international study involving researchers from the Hospital del Mar Research Institute reveals a key interaction between two proteins that are fundamental in tumour development

 

  • To achieve this, molecular modelling and artificial intelligence techniques were used, revealing for the first time a new structural model that describes a previously unknown cell-signalling mechanism

 

  • The research opens the door to designing drugs that act on the interaction between the two proteins, thereby improving current cancer treatments

 

An international research consortium, led by the University of Utah School of Medicine in Salt Lake City, United States, has discovered a new pathway that could enable the development of new cancer treatments. The study, published in the journal Nature Structural & Molecular Biology, involved researchers from institutions in the United States, Germany, Switzerland and Spain. Tomasz Maciej Stepniewski, co-first author of the study, and Jana Selent, who leads the G protein-coupled receptor-based drug discovery research group at the Hospital del Mar Research Institute, are the only authors from a Spanish centre.

In this study, the researchers used molecular modelling techniques and artificial intelligence tools for the first time, allowing them to design experiments and resolve the structure of the proteins studied. Specifically, they examined the relationship between a cellular receptor protein, Smoothened, which is involved in the development of tumours such as basal cell carcinoma, medulloblastoma and some pancreatic and lung cancers, and the protein PKA, or protein kinase A. The study discovered how Smoothened blocks the action of PKA, whose function is to help control cell growth. When this happens, cells can grow more easily and cause tumours.

“This is an important advance because it redefines the way scientists understand how cellular receptors function, revealing a new mechanism by which these receptors can transmit signals inside the cell”, explains Stepniewski. Thanks to the use of advanced artificial intelligence models, the researchers were able to analyse and predict molecular-level interactions between the proteins, revealing a previously unknown interaction mechanism. “This finding reveals a distinct signalling mechanism, in which the receptor not only activates reactions indirectly, but also establishes direct contact with a key protein in the pathway”, he adds.

Treatments focused on the direct interaction between proteins

Current treatments that target Smoothened aim to completely deactivate this protein, which can cause side effects or lead them to lose effectiveness over time. Their design was based on static receptor structures and experimental assays. By understanding the mechanism of direct interaction between this receptor and PKA, researchers can “design new and more precise treatments that restore the cell’s natural control capacity instead of completely deactivating it”, according to Jana Selent. This discovery opens the door to more effective therapies that act directly on this interaction and have fewer side effects for patients. In other words, “a new path for the development of cancer drugs”.

The team responsible for the study believes that its conclusions may be applicable to other receptors involved in tumour development. The next step will be to develop new molecules capable of acting on this mechanism and test them in preclinical models. To support this work, the researchers have made the models they created available free of charge to other scientists and companies.

Reference article

Steiner, W.P., Iverson, N., Liu, G. et al. Structural mechanism for noncanonical GPCR signaling in the Hedgehog pathway. Nat Struct Mol Biol (2026). https://doi.org/10.1038/s41594-026-01800-z

Further information

Communication Department, Hospital del Mar Research Institute/Hospital del Mar: Marta Calsina 93 3160680 mcalsina@researchmar.net, David Collantes 600402785 dcollantes@hospitaldelmar.cat

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GRIB hosts guest researcher Carlo Colantuoni for a seminar and workshop on multi-omics data analysis https://grib.upf.edu/grib-hosts-guest-researcher-carlo-colantuoni-for-a-seminar-and-workshop-on-multi-omics-data-analysis/ https://grib.upf.edu/grib-hosts-guest-researcher-carlo-colantuoni-for-a-seminar-and-workshop-on-multi-omics-data-analysis/#respond Fri, 17 Apr 2026 09:13:10 +0000 https://grib.upf.edu/?p=2288 GRIB will host Carlo Colantuoni (Johns Hopkins University) on April 21st at PRBB for a seminar and hands-on workshop on multi-omics data analysis. The session will cover NeMO Analytics and advanced methods for integrating complex biological datasets.

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The Research Programme on Biomedical Informatics (GRIB) will host a special seminar and hands-on workshop on April 21st at the Barcelona Biomedical Research Park (PRBB), featuring guest researcher Carlo Colantuoni from Johns Hopkins University School of Medicine.

Organised by the Neurogenomics Group, the session will focus on recent advances in the analysis and integration of multi-omics data, with applications to brain development, neurodegeneration, and complex biological systems.

The programme will include three sessions:

  • 14:30 – NeMO Analytics and neocortical development using stem cell models. 
  • 15:30 – Using NeMO Analytics to explore public multi-omics datasets (no coding required)
  • 16:30 – Structured Joint Decomposition to integrate multiple related multi-omics datasets (advanced session for coders)

 

The workshop will take place in the Marie Curie Room and is open to researchers across the PRBB community.

As a joint programme of the Hospital del Mar Research Institute and Pompeu Fabra University, GRIB brings together multidisciplinary expertise in bioinformatics and computational biology to better understand human health and disease through data-driven approaches.

This event represents an excellent opportunity to engage with state-of-the-art tools for multi-omics data exploration and to foster collaboration within the PRBB scientific community.

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Broad collaboration produces high-resolution atlas of developing human brain https://grib.upf.edu/broad-collaboration-produces-high-resolution-atlas-of-developing-human-brain/ https://grib.upf.edu/broad-collaboration-produces-high-resolution-atlas-of-developing-human-brain/#respond Tue, 07 Apr 2026 08:31:07 +0000 https://grib.upf.edu/?p=2282 Johns Hopkins & GRIB researchers have enhanced a cellular road map of how the brain forms and adapts early in life, bringing together nearly 200 studies and 30 million cells

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John Hopkings Magazine

26/03/2026

In a bid to better understand, and potentially treat, a host of conditions that affect early cognition, neurodevelopment, and the brain later in life, investigators at Johns Hopkins Medicine and colleagues around (GRIB, Hospital del Mar Research Institute) the world have been mapping the molecular construction of the human brain. These models, which are supported in part by federal and international research grants, are helping researchers study genetic links and pathways involved in a variety of conditions, ranging from autism spectrum disorder to Alzheimer’s disease.

To support this blueprint, Carlo Colantuoni, an adjunct professor of neurology at Johns Hopkins Medicine and the Institute for Genome Sciences at the University of Maryland School of Medicine, and other researchers have, in their most recent study, brought together data from nearly 200 published studies and more than 30 million cells to advance insight about how the neocortex (the outermost layers of the brain) develops and forms over time. This region of the brain is responsible for a variety of functions, including how we think, sense, process and store information, and make decisions.

“Our goal is to understand how the neocortex is built on a cellular level, and identify clues to the earliest stages of developmental delays and brain disorders,” Colantuoni says. “By mapping the cell transitions and genes that give rise to the intricate structure and function of the neocortex, we can better understand, and then attempt to treat, disorders that arise in the womb, during infancy and childhood, and even much later in life.”

This enhanced atlas will help researchers study genetic links for autism spectrum disorder, which affects about 1 in 31, or 3%, of children in the U.S. It can also provide insight into rare conditions like microcephaly, which can begin before birth and drastically affect the growth of the brain. A strength of bringing this information together—it is now available through Nature and Nature Neuroscience—is that researchers can study granular stages of development to identify typical growth patterns and then pinpoint the origins and pathways of neurodevelopmental delays and disease.

In addition to mapping a human model of the neocortex, the authors published a mammal and mouse model. These different atlases show that gene expression programs that began as diffuse networks millions of years ago were more recently focused in human neural stem cells to drive expansion of the human neocortex. This process, the researchers say, helped contribute to and, in part, explains differences in higher human cognitive abilities compared with other animals.

Using the accumulated data, the researchers also charted the maturation of neurons in the human neocortex, a process that has become longer over evolutionary time as the human neocortex and mental capacity have expanded. For example, this type of neural development takes weeks in a mouse but many years in humans. This represents differences in advanced systems that enable the human brain to adapt and learn how to interpret complex social, environmental, and sensory inputs over an extended developmental period.

These resources are now available via an open-access web portal to empower other researchers investigating human brain development and disease. Collectively, says Colantuoni, these and other brain-charting efforts aim to help researchers study mechanisms of brain disease throughout the lifespan and provide a tool to better support and accelerate everyday research.

The image shows how different elements of the genome are used during the birth of neurons in the mouse, monkey, and human brain.

Researchers without coding expertise can explore the expression patterns of individual genes of interest, chart the coordinated expression of gene modules that work together in specific ways during development, and contribute their own data to expand the resource.

Previous Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative efforts have generated human and mouse brain cell censuses, which catalog the diversity of cell types in the mammalian brain. Other projects are exploring how opioid use affects the brain of those living with HIV, how hair cells within the inner ear could be regenerated to restore hearing, and how cellular pathways are distributed in dementia, including Alzheimer’s disease, which is estimated to affect more than 7 million U.S. adults, including 1 in 9, or 11%, age 65 and older.

These brain-mapping studies are complemented by broader efforts to chart the entire cellular landscape of the human body, including the Human Cell Atlas, or HCA. The HCA was founded in 2016 with the goal of bringing investigators around the world together to create open-access resources to map every cell in the human body. In 2024, experts published insights from more than 40 papers examining 62 million cells from nearly 10,000 humans.

Research from the HCA and related studies has already led to the discovery of new lung cells, a greater understanding of how the body responds to infections, and identification of networks of cells that work together to help the heart beat, regulate heart rate, and enable communication among organs throughout the body.

“We’re living in an unprecedented time, when advancements in using technology to coordinate and analyze large datasets, work with researchers throughout the world, and leverage insights across disease states is paramount to identifying new treatments that can save and improve lives,” Colantuoni says. “As these initiatives reach major milestones, we’re also seeing that the way investigators can collaborate and use these atlases is just getting started.”

Colantuoni adds that it is critical to recruit more academic and industry partners to invest in these precompetitive data exploration spaces that will greatly expand identification of novel molecular targets for treating brain disorders.

“Combined with AI algorithms to guide large-scale screening in stem cell systems, these resources promise to enable precision tailoring of treatments to help individual patients with neurodevelopmental and neurodegenerative disease,” he says.

To support this vision, Colantuoni and colleagues, including Paul Worley, Jin-Chong Xu, Xiangyu Liao, and Yuelin Lao (all from Johns Hopkins Medicine), Carol A. Barnes (from the University of Arizona), and Matthew Huetelman and Ignazio S. Piras (from TGen, the Translational Genomics Research Institute), have also created an open-data resource focused on Alzheimer’s disease.

Other authors of the neocortical development paper include Shreyash Sonthalia, Ricky S. Adkins, Joshua Orvis, Guangyan Li, Xoel Mato Blanco, Alex Casella, Jinrui Liu, Genevieve Stein-O’Brien, Brian Caffo, Ronna Hertzano, Anup Mahurkar, Jesse Gillis, Jonathan Werner, Shaojie Ma, Nicola Micali, Nenad Sestan, Pasko Rakic, Gabriel Santpere, and Seth A. Ament.

The research described in the new report was supported in part by a PTE federal award, NIH research grants, the NIDCD/NIH Intramural Research Program, international awards, and the Johns Hopkins University Discovery Award. The authors have no disclosures to report.

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Gabriel Santpere co-first author in the new paper published in Nature:”Adaptive evolution of gene regulatory networks in mammalian neocortex” https://grib.upf.edu/gabriel-santpere-co-first-author-in-the-new-paper-published-in-natureadaptive-evolution-of-gene-regulatory-networks-in-mammalian-neocortex/ https://grib.upf.edu/gabriel-santpere-co-first-author-in-the-new-paper-published-in-natureadaptive-evolution-of-gene-regulatory-networks-in-mammalian-neocortex/#respond Fri, 20 Mar 2026 10:09:36 +0000 https://grib.upf.edu/?p=2278 In the new paper published in Nature:" Adaptive evolution of gene regulatory networks in mammalian neocortex", Gabriel Santpere is the co-first author. The paper explains the role of Zbtb18 in the evolution of excitatory neuron diversity in mammals.

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20/03/2026

In the new paper published in Nature:”Adaptive evolution of gene regulatory networks in mammalian neocortex”, Gabriel Santpere is the co-first author. The paper explains the role of Zbtb18 in the evolution of excitatory neuron diversity in mammals. In collaboration with Nenad Sestan, who led this work and the multidisciplinary team, including Zhuo Li, Kaur Navjot, Sydney Muchnik, PhD, Suvimal Kumar Sindhu, Cai Qi, Mikihito and many others. Also, Xabier de Martin, member of the neurogenomics group and member of the GRIB, has participated.

Abstract

Mammals have evolved a more complex brain, exemplified by the transformation of the single-layer dorsal cortex of excitatory projection neurons (ExNs) in ancestors into a multilayered cerebral neocortex1,2,3,4 enriched with diverse intratelencephalic and extratelencephalic ExN subtypes5,6,7, thereby establishing specialized projection systems that enhance brain connectivity and functionality5,6,7,8. This is in contrast to modern reptiles and birds with single-layered or pseudolayered columnar organization of ExNs4,9,10,11,12. However, the mechanisms underlying these mammalian-specific adaptations remain elusive. By comparing the landscape of gene expression and putative cis-regulatory elements (CREs) in mouse ExN subtypes and through cross-species examination, we identified mammalian-specific CREs, including a subset bound by the transcription factor ZBTB18 (also RP58, ZFP238 or ZNF238) and associated with genes defining intratelencephalic and extratelencephalic subtypes and connectivity, which have been implicated in intellectual disability and autism. Deletion of Zbtb18 in mouse ExNs dysregulated target gene expression, reduced molecular diversity, diminished cortico-spinal and callosal projections and increased intrahemispheric cortico-cortical association projections to the prefrontal cortex, thereby resembling non-mammalian brain. ZBTB18 binding motifs are highly enriched in callosally projecting intratelencephalic-biased putative CREs and show higher conservation specifically in mammals. This study uncovers critical components and mammalian-specific evolutionary adaptations within a regulatory node essential for neocortical ExN identity and connectivity.

You can read the paper here: https://www.nature.com/articles/s41586-026-10226-y#Sec41

La entrada Gabriel Santpere co-first author in the new paper published in Nature:”Adaptive evolution of gene regulatory networks in mammalian neocortex” se publicó primero en GRIB.

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