30.10.2018 – LifeTime scientists and colleagues call for new standards
Scientists call for unified standards in 3D genome and epigenetic data
Studying the three-dimensional structure of DNA and its dynamics is revealing a lot of information about gene expression, expanding our knowledge of how cells, tissues and organs actually work in health and disease. Properly producing and managing this large amount of data is both challenging and necessary for the progress of this field. In a perspective paper published in Nature Genetics, top researchers call for unified standards and suggest guidelines in this emerging and promising research area.
Just as a map of the world is more than a list of places and street names, the genome is more than a string of letters. A complex choreography of proteins and nucleic acids interact differentially over time in the DNA, thus cells can selectively manage genetic information during development and cell differentiation or in response to physiological and environmental aspects.
Scientists worldwide are developing new technologies and making progress towards understanding the dynamics of three-dimensional organization of the nucleus. This new approach will allow researchers to map the differences between cell types, to explore how gene expression actually works in health or disease, and to discover how DNA functions are achieved even it is packed within the tiny nucleus.
“We know that genome folding and its dynamics modulates gene expression and new technologies allow us to build 3D models to study these changes, which is currently shaking up genome research and boosting our understanding of the cell nucleus complexity,” explains Marc A. Marti-Renom, ICREA research professor at the Centro Nacional de Análisis Genómico of the Centre for Genomic Regulation (CNAG-CRG) in Barcelona, Spain. “This is an absolutely promising field and we would like to call for standards since the rapid development of methods and the increasing complexity of data pose many challenges that must be addressed now,” he states.
In a perspective article published in the current issue of Nature Genetics, top leading scientists in the field of dynamics and structural genomics have called for standards in 3D genome and epigenetic data. They describe the main challenges in this field and provide guidelines to think about strategies for shared standardized validation of 4D nucleome data sets and models.
This paper comes out of their experience in the 4D Nucleome Initiative as part of the LifeTime initiative for a new FET-Flagship in Europe to understand how genomes function within cells, and how cells form tissues and dynamically remodel their activities when tissues progress towards disease.
With this call for standards, international experts at the Institut Curie in Paris, MRC Institute of Genetics and Molecular Medicine at Univeristy of Edinburgh, the Centre de Biologie Intégrative at the University of Toulouse, the Institute of Human Genetics in Montpellier, the Babraham Institute in Cambridge, the Florida State University in Forida (US), the Friedrich Miescher Institute for Biomedical Research in Basel, the Napoli University, the Berlin Institute of Health, the Institute for Research in Biomedicine IRB Barcelona, the Max Delbruck Center for Molecular Medicine in Berlin, the Institute for Epigenetics and Stem Cells Helmholtz Zentrum Muenchen in Munich, and the Centro Nacional de Análisis Genómico of the Centre for Genomic Regulation (CNAG-CRG) in Barcelona, want to ensure that information is properly characterized, validated and shared, and that resources are efficiently used.
18.09.2018 – 2nd stage proposal submitted!
The LifeTime initiative, which strives to build a new European FET-Flagship, has set sail for the next harbour: on Tuesday 18 September the proposal for a Coordination and Support Action (CSA) has been submitted to the European Commission. CSAs are preparatory actions, funded with €1 Mio for one year, with the aim to prepare the full Flagship application. The results are expected towards the end of 2018, with a CSA starting approximately half a year later.
LifeTime is the shared vision of more than 120 leading scientists at over 50 renowned organisations across Europe, who selected 18 partners to lead the preparatory work for the FET-Flagship.
LifeTime has gathered more then 60 partners from industry and received letters of support from major funding agencies, science academies and science and research ministries across Europe.
Many thanks to all the supporters, partners and contributors who helped the initiative to move one step closer to the realisation of the LifeTime vision.
22.03.2018 – LifeTime Press Release
LifeTime – a visionary proposal for an EU Flagship
Reliably predicting the onset and trajectory of a disease might seem like a distant dream. But a European consortium is aiming to achieve exactly this using a set of emerging technologies with the analysis of single cells at their core. Leading scientists have now submitted the proposal for a FET Flagship called LifeTime.
Following the completion of the Human Genome Project in 2001, scientists and the media described the genome as “the book of life”, holding the answers to the way genes are linked to disease. Yet, seventeen years later, we are still deciphering how cells interpret this book.
Since then, so-called Omics technologies have flourished, allowing researchers, for example, to observe and quantify thousands of gene products in a single tissue sample. Omics experiments used to require tens of thousands of cells. But in the last couple of years, novel single-cell methods have emerged which enable scientists to perform such global analyses in individual cells. The molecular make-up of tissues and organs can now be assessed at single-cell resolution.
Snapshots are not enough
Mapping and analyzing tissues at the single-cell level is highly informative and challenging by itself, but a diverse group of 60 scientists across Europe decided that merely taking snapshots is not enough. Cells are highly dynamic entities and may even change identities. To understand molecular forces behind different cell states in development, aging and disease, these scientists want to track the molecular make-up of human cells in time and space. To this end, they formed the LifeTime consortium with the goal of establishing an integrated toolbox containing several novel revolutionary methods.
Single-cell technologies will be applied to experimental model systems such as organoids, miniature organs grown in the petri dish from one or more cells. Combined with the genome editing tool CRISPR/Cas as well as state-of-the-art microscopy, these models will help to understand how cells stay healthy or progress towards disease and react to therapeutics. Importantly, LifeTime scientists will also develop computational strategies such as powerful machine-learning and artificial intelligence methods that help to understand molecular mechanisms and predict the future of a patient’s tissue or even means to steer the tissue towards health. This strategy is expected to improve early diagnoses and intervention, predict the course of a disease, identify new drug targets and select the most effective therapies for individual patients.
A group of pioneers
Future and Emerging Technologies Flagships (such as the ongoing Human Brain Project, the Graphene and the Quantum Technologies Flagship) are funded by the European Commission with one billion Euros for ten years. The competition for the next two Flagships has just started, and proposals have been submitted. LifeTime – jointly coordinated by the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) in Berlin and the Institut Curie in Paris – is one of them.
Currently the LifeTime consortium consists of over 60 leading single-cell biologists, computer scientists, mathematicians, clinicians, pathologists, imaging experts, and physicists from over 50 European institutions in 18 countries. They are pioneers in their disciplines, working towards a common vision of future medicine, and would like LifeTime to be an open endeavor that will attract new talents and integrate all scientists in Europe who can make a significant contribution. Their unique collective network will transcend institutional boundaries and improve the overall infrastructure for the life sciences in Europe, with a focus on training for the next generation of scientists.
Steer life sciences and healthcare to the future
The LifeTime consortium will build on the achievements of the Human Cell Atlas (HCA), an international project launched about a year ago. The HCA aims to create a map of healthy tissues with single-cell technologies, thereby capturing the enormous diversity of cell types within those tissues. LifeTime proposes to go far beyond providing static tissue maps and to track, understand and predict how the molecular make-up of cells changes during human diseases and ultimately intervene.
It is a vision that can steer both life sciences and healthcare into the future and kick-start a single-cell innovation ecosystem in Europe. Many technologies at the center of LifeTime are key European research strengths that the Flagship could boost. These include single-cell technologies combined with advanced imaging, artificial intelligence and patient-matched organoids, or organ-on-a-chip disease models to study the progression of an illness and develop novel therapeutics.
Inspiration from Renaissance Europe
As an inspiration, LifeTime scientists name Renaissance Europe. Back then, new types of telescopes permitted Brahe, Galileo and Kepler to accurately map the precise positions of stars and planets. They were able to decode the patterns in these maps thanks to new types of mathematics developed by Leibniz and Newton, and thus discovered that celestial bodies moved in rule-governed and therefore predictable ways. Their efforts reshaped the society of their time.
Similarly, emerging technologies now allow scientists to observe cells (corresponding to planets in this analogy) and entire organs (corresponding to solar systems) with unprecedented precision. New mathematical and computational tools will be required to understand the movement and relationships of those cells. The resulting ability to explain cellular changes as they age or progress towards disease will fundamentally change our perception of how organisms function and will greatly advance medicine.
The LifeTime consortium
The more than 60 scientists and clinicians forming the LifeTime consortium are distributed over 18 European countries and 52 institutions. Both the Helmholtz Association of German Research Centres and the French National Center for Scientific Research CNRS – two of the biggest science organizations in Europe – have pledged their strong support. Furthermore, the consortium is endorsed by Science Academies such as the German National Academy of Sciences Leopoldina, the French Academy of Sciences, the Royal Society and the Royal Netherlands Academy of Sciences and Arts and the EU-life Alliance. Professor Nikolaus Rajewsky, Director of the Berlin Institute for Medical Systems Biology at the Max Delbrück Center for Molecular Medicine, and Professor Geneviève Almouzni, CNRS senior researcher and director of the research center at Institut Curie in Paris, are jointly coordinating the LifeTime proposal.
Participating institutions: Helmholtz Association • CNRS • Institute of Molecular Biotechnology • Research Center for Molecular Medicine of the Austrian Academy of Sciences • VIB-KU Leuven • Friedrich Miescher Institute for Biomedical Research • University of Basel • University of Zurich • Central European Institute of Technology • Max Planck Institute of Immunobiology and Epigenetics • Max Planck Institute for Molecular Genetics • German Cancer Research Center • Max Delbrück Center for Molecular Medicine • German Center for Neurodegenerative Diseases • Helmholtz Zentrum München • Max Planck Institute for Evolutionary Anthropology • Helmholtz Institute of RNA-based Infection Research • Saarland University • Technical University Munich • University of Würzburg • Biotech Research & Innovation Centre • Interdisciplinary Nanoscience Center • University of Copenhagen • Centre for Genomic Regulation • Institut Curie • Université de Montpellier • Inserm • Université Toulouse III – Paul Sabatier • École nationale supérieure des mines de Paris • Institute for Molecular Medicine Finland • The Biomedical Research Foundation, Academy of Athens • Weizmann Institute of Science • Hebrew University • Sapienza – University of Rome • Instituto Nazionale Genetica Molecolare • University of Napoli • University of Padua • University of Milan • European Institute of Oncology • Netherlands Cancer Institute • Radboud University • University Medical Center Utrecht • Hubrecht Institute • Instituto Gulbenkian de Ciência • Institute of Bioorganic Chemistry of the Polish Academy of Sciences • Romanian Center for Systems Immunology • Karolinska Institute • MRC Human Genetics Unit • University of Edinburgh • Wellcome Sanger Institute • The Babraham Institute • European Molecular Biology Laboratory – European Bioinformatics Institute