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.

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.

La entrada ORFeus, boosting research into the dark proteome se publicó primero en GRIB.

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-

La entrada Mar Albà to participate in the “Genome Dark Matter” mini-symposium celebrating the 25th anniversary of the Human Genome se publicó primero en GRIB.

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

La entrada A new study names part of the human genome se publicó primero en GRIB.

• 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

La entrada A new pathway for developing cancer drugs discovered se publicó primero en GRIB.

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.

La entrada GRIB hosts guest researcher Carlo Colantuoni for a seminar and workshop on multi-omics data analysis se publicó primero en GRIB.

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.

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.

La entrada Broad collaboration produces high-resolution atlas of developing human brain se publicó primero en GRIB.

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

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.

17/03/2026

The Evolutionary genomics group has done another preprint on bioRxiv: “Oncogenes and tumor suppressor genes are enriched in stop-loss mutations generating protein extensions”Analysis of stop-loss mutations in > 20,000 cancer samples shows that several oncogenes and tumor suppressor genes are recurrently mutated.

You can read the preprint here: https://www.biorxiv.org/content/10.64898/2026.03.12.711331v1

La entrada New preprint on BioRxiv: “Oncogenes and tumor suppressor genes are enriched in stop-loss mutations generating protein extensions” se publicó primero en GRIB.

17/03/2026

The study, led by Suel-Kee Kim, Adriana Cherskov, and Nenad Sestan, on human-specific cerebellar biology and the unexpected role of ZP2. GRIB has contributed with excellent work from Xoel Mato and Jose Manuel Ruiz. members of the neurogenomics group led by Gabriel Santpere.

Summary

La entrada GRIB has contributed in a new study:”Human-specific features of the cerebellum and ZP2-regulated synapse development” se publicó primero en GRIB.

11/03/2026

A new preprint on bioRxiv: “Evolutionary emergence and preservation of microproteins encoded by upstream ORFs” how the evolutionary genomics group use Nanopore dRNA and Ribo-Seq data from multiple yeast species to discover tens of highly conserved microproteins encoded by uORFs in polycistronic transcripts/alternative isoforms.

ABSTRACT

The analysis of ribosome profiling (Ribo-Seq) data has provided evidence that many eukaryotic mRNAs contain translated upstream or downstream ORFs (uORFs/dORFs), but the biological significance of this translation activity remains, for the most part, unknown. One of the principal limitations has been the lack of Ribo-Seq data from several closely related species, precluding the identification of cases in which translation is phylogenetically conserved. Here, by combining Ribo-Seq data from 100 different experiments, we identify 2,332 translated uORFs and 1,008 translated dORFs in S. cerevisiae, which result in microproteins that tend to be highly hydrophobic or positively charged. To study their phylogenetic conservation, we have generated Nanopore direct RNA sequencing data, together with Ribo-Seq data, from six additional Saccharomyces species, spanning an evolutionary period of around 16 million years. We have identified 195 translated S. cerevisiae uORFs that are also translated in other Saccharomyces species; these uORFs are translated at levels comparable to the main coding sequence and display signatures of purifying selection at the level of the encoded microproteins. In contrast, dORFs are translated at very low levels and they are rarely conserved, suggesting much more limited microprotein functionalization. We have also discovered that uORF translation is associated with the formation of alternative transcript isoforms encompassing the region containing the uORFs but not the main protein coding sequence, implying that some microproteins can be produced independently of the main protein product. This work significantly advances our understanding of how initially pervasive uORF translation can result in new microproteins, providing many new candidates for further functional studies.

You can read the preprint here: https://www.biorxiv.org/content/10.64898/2026.03.05.709866v1 

La entrada New preprint on BioRxiv by Evolutionary genomics group se publicó primero en GRIB.