Our group has published a new study in Nature Cell Biology that contributes one important step towards elucidating the molecular mechanisms that some stem cells use to renew themselves while generating daughters that differentiate. Using as a model system the Drosophila neuroblast, the neural stem cell that generates the fly’s neural tissue, we identified a protein, named Centrobin that plays a key role in stem cell division.The study focuses on the cell organelle known as “centrosome”, which organises the microtubule network. In most animal cells, from worms to humans, a typical centrosome is composed of two barrel-shaped structures called “centrioles” surrounded by pericentriolar material that has a strong microtubule nucleation activity. For each centriole pair, one of the centrioles, called “mother”, is one cell cycle older than the other, called “daughter”. Previous results from our lab have shown that in Drosophila neuroblasts during interphase only the daughter centriole is embedded in pericentriolar material, forming a structure that organises a large microtubule array that plays a key role in instructing the orientation of the next cell division. When the cell divides, the daughter centriole is retained by the renewed neuroblast.This new study reports that Centrobin is both necessary and sufficient to enable daughter centrioles to bind the pericentriolar material that organises the interphase microtubule aster in Drosophila neuroblasts. Centrobin is present in daugther centrioles and absent in mother centrioles (Figure 1). The published article shows that daughter centrioles experimentally depleted of Centrobin cannot bind pericentriolar material while mother centrioles modified to carry Centrobin can. We also show that Centrobin physically binds to a set of known centriolar and pericentriolar material proteins, thus identifying a molecular pathway that might account for Centrobin’s function. Remarkably Centrobin can only perform its function if phosphorylated by Polo, hence revealing an interphase role of this essential kinase in daughter centriole retention by Drosophila neural stem cells.An article published last year by scientists working in the Division of Cancer Diagnosis in the Saitaman Cancer Center, in Japan, showed that when human neuroblastoma cells divide, the daughter cell that retains higher self-renewal potential frequently inherits the daughter centro
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 24 publications 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
Key protein in stem cell division identified (2013)
González Hernández, Cayetano (IRB Barcelona)view details
Light-regulated stapled peptides to inhibit protein-protein interactions involved in clathrin-mediated endocytosis (2013)
Gorostiza Langa, Pau (IBEC)view details
Most biological processes are mediated by protein-protein interactions (PPIs), which have emerged as important pharmacological targets. Peptide inhibitors with nanomolar affinities were recently developed and demonstrated anticancer activity in vivo. In order to dissect the precise orchestration of PPIs in cells, it would be very useful to complement the pharmacologic selectivity of inhibitors with a means of remotely controlling their kinetics and site of action. Here, we present a peptide design and screening method to obtain photoswitchable inhibitors of protein-protein interactions, and we apply it to photo-regulate clathrin-mediated endocytosis (CME) in living cells. The selective manipulation of CME with light using these peptides, named Traffic Lights (TL) because they act as stop & go signals for membrane traffic, constitutes a novel tool to control cell signaling in spatiotemporally defined patterns. TL peptides can be applied to dissect the role of CME in complex cellular functions like receptor internalization, cell growth, division and differentiation.
Uncovering and preserving South Africa's rich precolonial heritage (2013)
Jerardino Wiesenborn, Antonieta (CSIC - IMF)view details
“The Archaeology of the West Coast of South Africa” is a peer-reviewed volume that presents updated contributions from specialists in the fields of coastal shell midden archaeology, zooarchaeological studies, GIS spatial analyses, geoarchaeology, ceramic and lithic technology, physical anthropology, historical archaeology, and heritage management. An introductory chapter discusses the role and history of archaeological research in this region followed by ten chapters focusing in different sub-regions and above topics. As reflected in this book, the West Coast of South Africa holds one of the largest, most ancient and richest archives of the human history in the world. Spreading 1 million years and a diversity of environments, this record of human presence represents a privileged window into the various stages of technological and behavioral evolution. The cultural heritage of the West Coast of South Africa includes also some of the most ancient rock art in southern Africa. This constellation of distinctive factors makes this region a vital source of discussions for international scholars in diverse topics such as: Pleistocene tool manufacture and mobility, the emergence of modern human behavior, forager and herder land use patterns and cultural contact situations as well as possible competition between these groups, population dynamics and funerary contexts, human impact on marine and terrestrial resources, emergent social complexity among initial egalitarian hunter-gatherer groups, and the irreversible impact of colonial presence that brought a new social and economic order that shapes the South African nation today. About twenty separate and major research projects (academic and contract archaeology (CA)) in collaboration with North American and European research institutions have been conducted over the last fifteen years in this geographic area. Although several of these CA projects have been described in less accessible accounts and in the so-called “grey literature”, these reports are now reflected in this book. The many contributing authors are leaders in their respective fields and have ensured a high and consistent academic quality throughout its length.
Pan-Cancer analysis of thousands of tumor genomes to identify cancer drivers (2013)
López-Bigas, Núria (UPF)view details
Identifying the complete list of genes involved in cancer development has been a major objective of cancer researchers for more than 30 years, as this is a first step towards the development of therapies that effectively and selectively target cancer genes to specifically kill tumour cells. In recent years systematic approaches to the quest for cancer genes have been undertaken. These involve sampling cancer genomes and sequencing most coding exons or the whole genome. Thousands tumour genomes are being sequenced in the world. Most have been generated as part of large projects and consortia, such as the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). When a tumour genome is sequenced, hundreds or even thousands of somatic mutations are detected; therefore, identifying which of those are involved in driving the tumourigenic process is a major challenge. With hundreds of available sequenced tumour genomes of each cancer type, this problem can be approached by identifying signals of positive selection in the pattern of mutations observed per gene across tumours. We have developed a computational approach to detect driver genes by combining multiple signals of positive selection and have applied it to 3,205 tumors from 12 different cancer types from the TCGA Pan-Cancer project (Weinstein et al., Nature Genetics 2013). We have identified 291 high confident cancer driver genes. Among those genes, some have not been previously identified as cancer drivers and 16 have clear preference to sustain mutations in one specific tumour type. The novel driver candidates complement our current picture of the emergence of these diseases (Tamborero et al., Scientific Reports 2013). In addition we have described IntOGen-mutations, a novel web platform for cancer genomes interpretation, which analyses not only TCGA pan-cancer data but also additional datasets generated by other initiatives such as those included within the ICGC. The resource allows users to identify driver mutations, genes and pathways acting on thousands of tumours from different cancer sites and to analyze newly sequenced tumor genomes and identify relevant mutations by putting them in the context of the accumulated knowledge (Gonzalez-Perez et al., Nature Methods 2013).
A new monograph on concentration inequalities (2013)
Lugosi, Gábor (UPF)view details
Oxford University Press published a new monograph onconcentration inequalities, written by Gábor Lugosi and his co-authors, Stéphane Boucheron and Pascal Massart.Concentration inequalities for functions of independent random variables is an area of probability theory that has witnessed a great revolution in the last few decades, and has applications in a wide variety of areas such as machine learning, statistics, discrete mathematics, and high-dimensional geometry. Roughly speaking, if a function of many independent random variables does not depend too much on any of the variables then it is concentrated in the sense that with high probability, it is close to its expected value. This book offers a host of inequalities to illustrate this rich theory in an accessible way by covering the key developments and applications in the field.The authors describe the interplay between the probabilistic structure (independence) and a variety of tools ranging from functional inequalities to transportation arguments to information theory. Applications to the study of empirical processes, random projections, random matrix theory, and threshold phenomena are also presented.A self-contained introduction to concentration inequalities, it includes a survey of concentration of sums of independent random variables, variance bounds, the entropy method, and the transportation method. Deep connections with isoperimetric problems are revealed whilst special attention is paid to applications to the supremum of empirical processes.
Great ape genetic diversity and population history (2013)
Marquès Bonet, Tomàs (UPF)view details
A new study has, for the first time, sequenced the genomes of a large number of Great apes from across Africa and South-East Asia. The work focused on characterizing as much wild genetic diversity as possible from the worlds rapidly dwindling great ape populations. Great apes are a group of species made up of humans and our closest relatives, chimpanzees, gorillas and orangutans. These species all share a common ancestor about 14-16 million years ago, but chimpanzees, for example diverged from humans much more recently, ~6 million years ago. The study provides one of the most detailed and comprehensive analyses of genetic diversity of wild-born great apes to date—species which are now all considered endangered. The researchers found that human genomes show relatively little variation between each other in comparison to most great apes. Few ape species are as shallow as human when it comes to genetic diversity. The genomes of a pair of orangutans, for example differ at more than 2 out of every 1000 base-pairs, compared to 1 out of every 1000 base-pairs between any two humans. A few species of great apes, however, were more similar to humans in that they showed a dearth of genetic variation; namely Eastern lowland gorillas, Western chimpanzees and bonobos. All of these species showed evidence of severe bottlenecks in their ancient history possibly explaining the reduced genetic diversity. The researchers focused particularly on the comparing the evolutionary history of our closest relatives, chimpanzees, who are dispersed across Africa and classified into four major groups, or, subspecies. An open question among evolutionary biologists has been how these four populations relate to one another. By sequencing multiple individuals from each group, the researchers were able to resolve the phylogenetic relationship among these subspecies distinguishing two genetically distinct groups of chimps. What also became apparent to the researchers was the complexity of the evolutionary history of chimps compared to humans. The patterns of genetic diversity were consistent with extensive gene flow or migration between ancestral populations with sudden expansions in population size followed by crashes. The basis for these population collapses is unclear but does coincide, in part, with a period of time when human p