Highlights

Every year, a committee of experts sits down with a tough job to do: from among all ICREA publications, they must find a handful that stand out from all the others. This is indeed a challenge. The debates are sometimes heated and always difficult but, in the end, a shortlist of  the most outstanding publications of the year is produced. No prize is awarded, and the only additional acknowledge is the honour of being chosen and highlighted by ICREA. Each piece has something unique about it, whether it be a particularly elegant solution, the huge impact it has in the media or the sheer fascination it generates as a truly new idea. For whatever the reason, these are the best of the best and, as such, we are proud to share them here.

LIST OF SCIENTIFIC HIGHLIGHTS

Format: yyyy

  • A novel factor to boost expansion of bone marrow-derived stem cells (2020)

    Cosma, Maria Pia (CRG)

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    A novel factor to boost expansion of bone marrow-derived stem cells

    Hematopoietic stem cells (HSCs) are responsible for the constant renewal of blood, producing billions of new cells every day. HSCs have unlimited potential to renew themselves for the entire lifespan of an organism, giving rise to every type of blood cell. HSCs have great potential in treating incurable cancers, autoimmune diseases and inherited blood disorders. However, just 1 in 2500 cells in the bone marrow are HSCs, a scarcity that limits their use in medical procedures.

    One way of obtaining more HSCs is by expanding the existing number found in the bone marrow, circulating blood or cord blood. A second way is by reprogramming other blood stem cells so that they acquire some of the self-renewing characteristics typical of HSCs. 

    In collaboration with the group of Andrea Califano (Columbia University, USA), we used an algorithm called VIPER to identify proteins capable of reprograming other blood stem cells. Out of eight potential candidates identified by the algorithm, just one – a gene known as BAZ2B – was able to significantly expand the number of HSCs in blood from the umbilical cord. 

    BAZ2B was able to reprogram blood stem cells to an HSC-like state by rearranging their chromatin, opening up unique regions in the genome that were previously inaccessible. The resulting cells successfully transplanted into the bone marrow of immunocompromised mice, could renew the growth of the tissue. 

  • Turbulent-like dynamics in the human brain (2020)

    Deco, Gustavo (UPF)

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    Turbulent-like dynamics in the human brain

    Most people know turbulence mainly from the experience of flying, yet turbulence is a fundamental feature of nature and found everything from rivers to galaxies.

    Giants of modern physics and mathematics like Andrey Kolmogorov, Yosihiki Kuramoto and Werner Heisenberg have succeeded in establishing some of the organising principles of turbulence. While most famous for his work in quantum physics, Heisenberg was equally obsessed with turbulence and discovered some of the fundamental statistical rules in 1946.

    Yet, it is only with the new paper ”Turbulent-like dynamics in the human brain” published in the leading open-access journal Cell Reports on  8 December 2020 that researchers have turned their attention to turbulence in the human brain. Resulting from an international collaboration between Center for Brain and Cognition at University Pompeu Fabra, Barcelona (Spain) and Department of Psychiatry, University of Oxford and Center for Music in the Brain, University of Aarhus, Profs Gustavo Deco and Morten L Kringelbach have discovered turbulent-like dynamics in human brain data from functional magnetic resonance imaging (fMRI) recordings from over 1000 participants.

    Previous research has shown that turbulence is the optimal way of cascading energy across spacetime over many scales, which is not just a visually pleasing phenomenon but as a fundamental organising principle of physical systems. It has also been shown to have significant relevant practical applications from improving chemical plants to airplanes and windmills. Our new results reveal a novel way of analysing and modelling whole-brain dynamics that suggests a turbulent-like dynamic intrinsic backbone facilitating large scale network communication. This new insight could revolutionise our understanding of brain function.

    Prof Kringelbach adds: “This new finding provides a novel yet solid framework that could be used for new biomarkers for neuropsychiatric disease. In the coming years, this framework could potentially lead to novel interventions that could improve the mental health of many people, especially after this turbulent pandemic”.

  • Extracellular vesicles play an important role in the pathology of ‘Plasmodium vivax’ malaria (2020)

    del Portillo Obando, Hernando A. (ISGlobal)

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    Extracellular vesicles play an important role in the pathology of ‘Plasmodium vivax’ malaria

    Plasmodium vivax is the most widely distributed human malaria parasite, mostly outside sub-Saharan Africa, and responsible for millions of clinical cases yearly, including severe disease and death. The mechanisms by which P. vivax causes disease are not well understood. Recent evidence suggests that, similar to what has been observed with the more lethal P. falciparum, red blood cells infected by the parasite may accumulate in internal organs and that this could contribute to the pathology of the disease.

     

    To understand the molecular mechanisms responsible for this adhesion process, the research turned its attention to extracellular vesicles. These small particles surrounded by a membrane are naturally released from almost any cell and play a role in communication between cells. There is increasing evidence that they could be involved in a wide range of pathologies, including parasitic diseases.

     

    The research team isolated EVs (Extracellular Vesicles) from the blood of patients with acute P. vivax infection or from healthy volunteers and showed a very efficient uptake of the former by human spleen fibroblasts. Furthermore, this uptake induced the nuclear translocation of NF-kB (Nuclear Factor Kappa B) with concomitant expression of a molecule (ICAM-1) on the surface of the fibroblast which in turn serves as an “anchor” for the adherence of P. vivax-infected red blood cells.

     

    These findings reveal, for what we believe is the first time, a physiological role of EVs in malaria and support the existence of parasite populations adhering to particular cells of the spleen, where they can multiply while not circulating in the blood”. “Importantly, these hidden infections could represent an additional challenge to disease diagnosis and elimination efforts as they might be the source of asymptomatic infections.   

  • A new study on Ewing sarcoma will pave the way for personalized therapy for childhood cancer (2020)

    Di Croce, Luciano (CRG)

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    A new study on Ewing sarcoma will pave the way for personalized therapy for childhood cancer

    1% of all childhood cancers are Ewing tumors. It mainly affects children and adolescents, but is also seen in young adults, with males slightly more affected than females.

    Researchers at the Centre for Genomic Regulation (CRG) and the Institut de Recerca Sant Joan de Déu have found that the RING1B gene is critical for the development of Ewing sarcoma, a rare type of cancer that affects bones or the tissue around bones and it account for 1% of all childhood cancers. This newly uncovered epigenetic vulnerability in Ewing sarcoma cancer cells opens the opportunity for new therapeutic strategies.

    The new study published in Science Advances reports that RING1B and EWSR1-FLI1 localize at the same regions in the genome, where RING1B is responsible for EWSR1-FLI1 recruitment. EWSR1-FLI1 cannot activate its target genes and transform a cell without RING1B.

     

    Base on this common interested the Centre for Genomic Regulation (CRG) and the Institut de Recerca Sant Joan de Déu want to extend the investigation to brainstem glioma, which mainly affects children, and at the moment there is no treatment, and it has a poor prognosis.

    The tumor is made up of very different cells that vary from patient to patient, and even change during the course of the disease itself. This makes it difficult to find an effective treatment.

    Until now, research on this tumor has been based on studies at the individualized cell level. Instead, the project cooridnated by Dr Luciano Di Croce in collaboration with Dr Mora (HSJD) and Dr. Marti-Renom (ICREA), and sponsored by la Caixa proposes multicellular reconstruction of the tumor in 3D, using personalized models of the patient in mice (PDX-patient derived xenograft). These models will allow testing individualized treatments for this type of cancer.

     

  • A cancer mystery of more than forty years ago is solved thanks to Epigenetics (2020)

    Esteller Badosa, Manel (IJC)

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    A cancer mystery of more than forty years ago is solved thanks to Epigenetics

    Before the first oncogene mutations were discovered in human cancer in the early 1980s, the 1970s provided the first data suggesting alterations in the genetic material of tumors. In this context, the prestigious magazine "Nature" published in 1975 the existence of a specific alteration in the transformed cell: an RNA responsible for carrying an amino acid to build proteins (transfer RNA) was missing a piece, the enigmatic nucleotide "Y". After that outstanding observation, the most absolute silence and ignorance has reigned for forty-five years on the causes and consequences of not having that correct base in that RNA. The article published in the Proceedings of the National Academy of Sciences (PNAS) by the group of Dr. Manel Esteller solves this mystery by describing that in cancer cells the protein that generates the nucleotide "Y" is epigenetically inactivated, causing small but highly aggressive tumors.

    Since the original discovery in 1975, there has been much biochemical work to characterize the enzymes involved in the different steps that lead to the desired nucleotide "Y", a hypermodified guanine, but without connecting this characterization with its defect in tumor biology. Dr Esteller’s work have built the bridge between these two worlds by demonstrating that the epigenetic silencing of the TYW2 gene is the cause of the loss of the elusive nucleotide "Y". Epigenetic blockade TYW2 gene occurs mainly in colon, stomach and uterine cancer. And it has undesirable consequences for healthy cells: the postman (RNA) that sends the signal to produce the bricks of our body (proteins) begins to accumulate errors and the cell takes on a different appearance, far from the normal epithelium, which we call mesenchymal and which it is associated with the appearance of metastasis. In this regard, when we study patients with colon cancer in early stages, the epigenetic defect of TYW2 and the loss of the nucleotide "Y" is associated with those tumors that, although small in size, already lead to less survival of the person.

  • The Talmud in the Christian World: A New Approach to Christian-Jewish Relations During the Middle Ages (2020)

    Fidora Riera, Alexander (UAB)

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    The Talmud in the Christian World: A New Approach to Christian-Jewish Relations During the Middle Ages

    Invited to speak at the honorary lecture series of the Albertus-Magnus-Institut in 2019, A. Fidora has now published a pioneering monograph in the prestigious Lectio Albertina-series which presents essential results of his ERC-project on "The Latin Talmud". This reappraisal of the history of the Jewish people in thirteenth-century Europe is a major contribution to historical and social justice. At the same time, exploring the historical interactions between Christians and Jews is crucial for understanding Europe’s cultural and political identity, which was shaped not only by Christianity, but also by Judaism and Islam. This study brings to light the historical foundations of religious (in)tolerance, and underscores the necessity of protecting religious and cultural diversity in Europe.

     

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