Genome Research Ltd.

Observing proteins precisely within cells is extremely important for many branches of research but has been a significant technical challenge -- especially in living cells, as the required fluorescent labeling had to be individually attached to each protein. The research group has now overcome this hurdle: With a method called 'vpCells,' it is possible to label many proteins simultaneously, using five different fluorescent colors. Observing proteins precisely within cells is extremely important for many branches of research but has been a significant technical challenge -- especially in living cells, as the required fluorescent labelling had to be individually attached to each protein. The research group led by Stefan Kubicek at CeMM has now overcome this hurdle: With a method called "vpCells," it is possible to label many proteins simultaneously, using five different fluorescent colours. This automated high-throughput approach, aided by AI-assisted image recognition, opens up entirely new applications in various disciplines, from fundamental cell biology to drug discovery. Without proteins, life as we know it would be inconceivable. They provide the structural framework for cells, act as enzymes to control metabolism, and enable cells to communicate with their environment as membrane receptors, transporters, or signalling molecules. All of these functions can only be fulfilled if the proteins are located in the right place within the cell. Often, even the properties of a protein change when it changes its location -- control over its localization in the cell therefore also means control over its function. To understand and explore the function of proteins, it is essential to precisely determine and track their location within the cell. Proteins often shuttle dynamically between different organelles and compartments of the cell. To visualize them under the microscope, they are often linked to a fluorescent, brightly shining protein component. However, this method has faced technical difficulties: Typically, the fluorescent component could only be attached to one protein at a time, and to label multiple proteins, cells usually had to be killed and fixed. The new method presented by Stefan Kubicek's group, called "visual proteomics Cells" (abbreviated vpCells), allows proteins to be fluorescently labelled in a way that preserves their endogenous regulatory mechanisms. Instead of labelling one protein at a time, vpCells can fuse many proteins simultaneously with a fluorescent tag in a so-called multiplex approach. A precursor of this method was already described by Kubicek's team in 2020 for studying metabolic enzymes (Reicher et al. Genome Res. 2020, DOI: 10.1101/gr.261503.120). Now it has been expanded and improved in three ways: Firstly, vpCells can label all theoretically possible proteins using the CRISPR/Cas9 gene-editing tool to genetically attach fluorescent proteins to the proteins under investigation. Kubicek's group has created a genome-wide "library" for this purpose, enabling the fluorescent marking and systematic functional exploration of all possible human proteins. Secondly, vpCells use not only one fluorescent colour but a total of five complementary colours. In each cell, two different proteins to be tracked are marked. Additionally, another colour marking is used to better distinguish individual clones. And two further colours mark the cell nucleus and membrane to delineate individual cells better. Thirdly, this colour scheme enables not only to generate visually appealing images, but also to optically recognize and discriminate the different proteins . Normally, this requires complex DNA sequencing after imaging to determine which protein is labelled. The vpCells approach, on the other hand, enables training an AI-assisted image recognition system to recognize which protein is marked in which cell based solely on fluorescence microscopy images. The method has already demonstrated its utility in two applications: On the one hand, more than 4,500 cell lines were generated as reporters for more than 1,100 proteins. These cell lines were used to train the AI models and to describe localization of the proteins in their basal state. All images of the individual labelled proteins are available on the publicly accessible web database vpcells.cemm.at. On the other hand, the living reporter cells were used for a specific research question: Kubicek's team examined the effect of more than 1000 small-molecule substances on 61 proteins relevant to cancer cells. The researchers found that 44 of the tested substances altered the amount or localization of individual proteins within 6 hours. One of the substances turned out to be an inhibitor of protein transport from the cell nucleus, which has a similar effect to a clinically approved drug for multiple myeloma, a cancer of the blood-forming system. "These results provide a first glimpse into the versatility of the vpCells method," says Kubicek. "We expect many more future applications , from fundamental cell biology to applied drug discovery."

Climate change and habitat destruction may have already caused the loss of more than one-tenth of the world's terrestrial genetic diversity, according to new research. This means that it may already be too late to meet the United Nations' proposed target, announced last year, of protecting 90 percent of genetic diversity for every species by 2030, and that we have to act fast to prevent further losses. Climate change and habitat destruction may have already caused the loss of more than one-tenth of the world's terrestrial genetic diversity, according to new research led by Carnegie's Moises Exposito-Alonso and published in Science. This means that it may already be too late to meet the United Nations' proposed target, announced last year, of protecting 90 percent of genetic diversity for every species by 2030, and that we have to act fast to prevent further losses. Several hundred species of animals and plants have gone extinct in the industrialized age and human activity has impacted or shrunk half of Earth's ecosystems, affecting millions of species. The partial loss of geographic range diminishes population size and can geographically prevent populations of the same species from interacting with each other. This has serious implications for an animal or plant's genetic richness and their ability to meet the coming challenges of climate change. "When you take away or fundamentally alter swaths of a species' habitat, you restrict the genetic richness available to help those plants and animals adapt to shifting conditions," explained Exposito-Alonso, who holds one of Carnegie's Staff Associate positions -- which recognizes early career excellence -- and is also an Assistant Professor, by courtesy, at Stanford University. Until recently, this important component has been overlooked when setting goals for preserving biodiversity, but without a diverse pool of natural genetic mutations on which to draw, species will be limited in their ability to survive alterations to their geographic range. In popular culture, mutations convey super powers that defy the laws of physics. But in reality, mutations represent small, random natural variations in the genetic code that could positively or negatively affect an individual organism's ability to survive and reproduce, passing down the positive traits down to future generations. "As a result, the greater the pool of mutations upon which a species is able to draw, the greater the chances of stumbling upon that lucky blend that will help a species thrive despite the pressures created by habitat loss, as well as shifting temperature and precipitation patterns," Exposito-Alonso added. He and his collaborators set out to develop a population genetics-based framework for evaluating the richness of mutations available to a species within a given area. They analyzed genomic data for more than 10,000 individual organisms across 20 different species to demonstrate that Earth's terrestrial plant and animal life could already be at much greater risk from genetic diversity loss than previously thought. Because the rate at which genetic diversity is recovered is much slower than that at which it is lost, the researchers consider it effectively irreversible. "The mathematical tool that we tested in 20 species could be expanded to make approximate conservation genetics projections for additional species, even if we don't know their genomes," Exposito-Alonso concluded. "I think our findings could be used to evaluate and track the new global sustainability targets, but there is still much uncertainty. We need to do a better job in monitoring populations of species and developing more genetic tools." "Moi took a bold, creative approach to probing a scientific question that's crucial for policymakers and conservationists to understand if they want to implement strategies that will meet the coming challenges our world faces," said Margaret McFall-Ngai, Director of Carnegie's newly launched Divison of Biosphere Sciences & Engineering. The research team included members of Exposito-Alonso's lab -- Lucas Czech, Lauren Gillespie, Shannon Hateley, Laura Leventhal, Megan Ruffley, Sebastian Toro Arana, and Erin Zeiss -- as well as collaborators Tom Booker of the University of British Columbia; Christopher Kyriazis of UCLA; Patricia Lang, Veronica Pagowski, Jeffrey Spence, and Clemens Weiß of Stanford University; and David Nogues-Bravo of the University of Copenhagen. This work was supported by a U.S. National Institutes of Health Early Investigator Award, the U.S. Department of Energy Office of Biological and Environmental Research, the Carnegie Institution for Science, Stanford's Center for Computational Evolutionary and Human Genomics, a Human Frontier Science Program Long-Term Fellowship, and the U.S. National Science Foundation's Plant Genome Postdoctoral Research Fellowship in Biology.

Atos supercomputer to help unlock secrets of the Universe Paris (France), London, (UK) 1 June 2021 – Atos today announces it has been awarded a contract by the University of Edinburgh to deliver its most efficient supercomputer, the BullSequana XH2000, the most energy-efficient supercomputing system on the market. This is the largest system dedicated to GPU computing deployed at a customer site in the UK. The new system will constitute the Extreme Scaling Service of the UK’s DiRAC HPC Facility. The state-of-the-art platform will allow scientists across the STFC theory community to drive forward world-leading research in particle physics, among other areas, using NVIDIA Graphics Processing Units (GPUs) and AMD processors. It represents a major boost to DiRAC’s computing capacity, significantly increasing the power of the Extreme Scaling service. DiRAC is a distributed facility with high performance computing resources hosted by the Universities of Edinburgh, Cambridge, Durham and Leicester. These systems support fundamental research in particle physics, astrophysics, nuclear physics and cosmology. This agreement forms part of a £20 million investment by the UK Research and Innovation (UKRI) World Class Laboratories scheme, through the Science and Technology Facilities Council (STFC), to fund an upgrade of the DiRAC facility. The investment is delivering new systems which are up to four times more powerful than the existing DiRAC machines, providing computing capacity that can also be used to address immediate and emerging issues such as the COVID-19 pandemic. The upgraded DiRAC-3 facility will also be much more energy efficient than previous generations. The new BullSequana XH2000 will be able to handle converged workloads simultaneously (HPC simulation, Artificial Intelligence, Deep Learning) on one single system, and therefore enable DiRAC to overcome the limits of traditional computing simulation and explore new applications and innovation. With cutting-edge networking standards and the latest processing components, it provides extreme power, speed and accuracy. It consumes less energy than current systems as it is 100% water-cooled using Atos’ patented DLC (Direct Liquid Cooling) solution, which minimises global energy consumption by using warm water up to 40°C. Agnès Boudot, Senior Vice President, Head of HPC & Quantum at Atos, said, “We are pleased to be partnering with the University of Edinburgh and the DiRAC community to provide a high-performance computing platform to support their world-class science programme. Our BullSequana XH2000 supercomputer will use both CPUs and GPUs and has been configured to meet the Extreme Scaling requirements of their scientists. This agreement continues to demonstrate our strategic commitment to design and build powerful and innovative supercomputers as we fast approach the exascale era.” Professor Mark Wilkinson, Professor of Astrophysics at the University of Leicester and Director of the DiRAC Facility, said, “It is fantastic that Atos has been successful in the DiRAC-3 procurement at Edinburgh and will become a valued partner of the DiRAC community. As well as delivering a highly capable solution, we are talking to Atos about the additional value they will bring in terms of industry collaboration and opportunities to enhance the training of our students to prepare them for careers in both academia and industry.” Professor Luigi Del Debbio, Professor of Theoretical Physics at the University of Edinburgh and Project Lead for the DiRAC-3 procurement at Edinburgh, said, “We are delighted that the delivery of this state-of-the-art supercomputing system will allow our scientific community in the fields of particle physics, astronomy, cosmology and nuclear physics to pursue cutting-edge research on a broad range of topics. Atos’ equipment and expertise will bolster our HPC system offering at the upgraded DiRAC-3 facility, strengthening our research activity and supporting the education and training of our students.” As part of on-going partnership activities, Atos will also help sponsor one student’s PhD, support a Hackathon and deliver a series of best practice training workshops for scientists. Atos is committed to supporting closer collaboration between academia and industry through the power of supercomputing and deep learning. In the UK, the company works in partnership with centres of excellence including The Science and Technology Facilities Council (STFC) Hartree Centre, Wellcome Genome Campus, the University of Oxford’s JADE service, and The Pirbright Institute, among others. *** About Atos Atos is a global leader in digital transformation with 105,000 employees and annual revenue of over € 11 billion. European number one in cybersecurity, cloud and high performance computing, the group provides tailored end-to-end solutions for all industries in 71 countries. A pioneer in decarbonization services and products, Atos is committed to a secure and decarbonized digital for its clients. Atos operates under the brands Atos and Atos|Syntel. Atos is a SE (Societas Europaea), listed on the CAC40 Paris stock index. The purpose of Atos is to help design the future of the information space. Its expertise and services support the development of knowledge, education and research in a multicultural approach and contribute to the development of scientific and technological excellence. Across the world, the Group enables its customers and employees, and members of societies at large to live, work and develop sustainably, in a safe and secure information space. About DiRAC DiRAC stands for Distributed Research Utilising Advanced Computing. The DiRAC High Performance Computing facility provides cutting-edge supercomputing resources for UK researchers working on world-leading scientific calculations across a wide range of areas including particle physics, astrophysics, cosmology and nuclear physics. It comprises supercomputers at Cambridge, Durham, Leicester and Edinburgh, each designed to support specific types of calculations. DiRAC also provides access to a team of expert research software engineers to help researchers make the most efficient use of the available computing resources. For more details see: . Press contacts: UK&I : Helena Shadbolt helena.shadbolt@mhpc.com +44 (0)20 3128 8799, Nick Collins nick.collins@mhpc.com +44 (0)20 3128 8897 Global: Laura Fau | laura.fau@atos.net | +33 6 73 64 04 18 | @laurajanefau Attachment