主题:Advanced imaging of cellular processes across scales

报告人:Prof. Jan Ellenberg




The recent resolution revolution in microscopy technologies allows unprecedented insights into the molecular machinery inside living systems. For the first time, imaging technologies have molecular resolving power and sensitivity and can be correlated to cover the whole range from structural detail of single molecules to imaging a whole living organism. This presentation will give examples at different scales where we have used advanced microscopy to study individual protein complexes, cellular signaling networks inside cells and aneuploidy causing cell division errors inside developing embryos.  The nuclear pore complex (NPC) is the largest macromolecular protein complex and mediates all nucleocytoplasmic transport through the nuclear envelope, each consisting of several hundred proteins. Due to this enormous size and complexity many details of its structure still remain elusive. We developed an approach that enables the reconstruction of a 3D molecular map by visualizing both scaffold and flexible nucleoporins, allowing us to address dynamic conformations and parts of the NPC that have been inaccessible for atomic resolution methods and opens the exciting possibility to observe NPC structure in different functional or assembly states. At the scale of protein networks, we established an integrated experimental and computational pipeline to build a 4D protein atlas of the dividing human cell, combining a collection of genome-edited fluorescent knock-in cell lines, absolutely quantitative live imaging and the integration and mining of this large data set by advanced bioimage analysis and machine learning. Our method is generic and makes many dynamic cellular processes now amenable to dynamic protein network analysis. At the scale of an embryo, we developed light-sheet microscopy to achieve the first in toto imaging of preimplantation mouse development from zygote to blastocyst, which was not previously possible due to their exquisite light sensitivity. We revealed when fate specification happens and that chromosome segregation is highly error prone in mouse embryos. With light-sheet microscopy, we are now able to study chromosome segregation, spindle formation and mitotic checkpoint control governing the first divisions of embryo mammalian life in real-time.


Research  Interests:

1. 4D Nucleome program 

Together with Ewan Birney's (EMBL-EBI Hinxton, UK) and Jonas Ries' (EMBL Heidelberg, GER) groups the Ellenberg lab will explore the physical 3D path of all DNA molecules (chromosomes) of the genome within the nucleus of a cell and will try to understand how this path changes during cell division. We aim at developing 3D and 4D super-resolution microscopy (SRM) technologies to enable us to determine the 3D structure of stable chromatin domains, resolve how such domains are interconnected and organized in 3D to form a chromosome, and monitor the structurally dynamic DNA sequences in real time during cell division.


Jan Ellenberg was awarded with an Advanced Grant by the European Research Council (ERC). The ERC promotes frontier research by outstanding scientists and selects projects based solely on scientific excellence. In COREMA we study cell division and the origin of embryonic aneuploidy in preimplantation mouse development. Cell division is fundamental for development. In the early mammalian embryo it drives the rapid proliferation of totipotent cells, the basis for forming the fetus. Given its crucial importance, it is surprising that cell division is particularly error-prone at the beginning of mammalian life, resulting in spontaneous abortion or severe developmental retardation, the incidence of which is increasing with age of the mother. Why aneuploidy is so prevalent and how early embryonic development nevertheless achieves robustness is largely unknown. The goal of this project is a comprehensive analysis of cell divisions in the mouse preimplantation embryo to determine the molecular mechanisms underlying aneuploidy and its effects on normal development. Recent technological breakthroughs, including light sheet microscopy and rapid loss-of-function approaches in the mouse embryo will allow us for the first time to tackle the molecular mechanisms of aneuploidy generation and establish the preimplantation mouse embryo as a standard cell biological model system. For that purpose we will develop next generation light sheet microscopy to enable automated chromosome tracking in the whole embryo. Mapping of cell division errors will reveal when, where, and how aneuploidy occurs, what the fate of aneuploid cells is in the embryo, and how this changes with maternal age.


In addition to his research activities, Jan Ellenberg is currently leading the implementation of Euro-BioImaging (EuBI) for EMBL, and in this regard he has scientifically coordinated this pan-European ESFRI research infrastructure project for biological imaging technologies during its submission to the ESFRI roadmap and the Preparatory Phase-I (2007-2014). Currently, he coordinates Euro-BioImaging Preparatory Phase II (2016-2017) and is the Scientific Coordinator for Global BioImaging (2015-2018). He represents EMBL in the Euro-BioImaging Interim Board together with Iain Mattaj (EMBL Director General) and Rainer Pepperkok (EMBL Head of Core Facilities). Jan is also the local coordinator of the EC funded “Combined Collaborative Project & Coordination & Support Action” for construction of new infrastructures “BioMedBridges” (2011-2015) and “CORBEL” (2015-2019), in which he coordinates the participation of Euro-BioImaging partners for biological imaging.

EuBI will act as the European research infrastructure in the field of biomedical imaging. The innovation-driven nature of EuBI facilities will strengthen Europe’s leading role in developing and implementing cutting-edge imaging technologies.Through EuBI, the provision of high quality services by one legal entity and the establishment of standardised access models to biomedical imaging technologies will foster national and European collaboration among research institutes, exchange of methods and expertise, and greatly accelerated access to emerging innovative imaging methods.

The imaging landscape not only in Europe changed significantly in the last 10 years, since imaging experts from 25 European countries joined their forces and draw the vision of a pan-European imaging infrastructure. As EuBI is coming closer to its full operation, European researchers are now taking the next step and, under the umbrella of the EC H2020 funded project Global BioImaging (GBI), reach out to their colleagues around the world. In the coming three years, they will work together with imaging infrastructure experts from Australia, Argentina, South Africa, India, Japan and the United States of America, to further open and improve provision of imaging services to biological and medical researchers worldwide. GBI is built on three existing collaboration agreements for successful operation of imaging infrastructures, which EuBI has signed with the Australian Microscopy and Microanalysis Research Facility (AMMRF), the National Imaging Facility (Australia) and India-BioImaging already during Preparatory Phase-I.

4. CORBEL – Setting the framework for common services by the ESFRI research infrastructures in biological and medical sciences

The CORBEL consortium comprises all ESFRI research infrastructures in the life sciences – including EuBI -, and it is coordinated by ELIXIR, the distributed research infrastructure for life-science data. CORBEL is a € 14.5 million project funded by EC H2020 for over four years, and provides the means to establish and support a new model for biological and medical research in Europe by harmonizing user access to resources, unifying data management and creating common ethical and legal services. The project builds on existing efforts within the BioMedBridges project and others to develop the tools, services and data management required by cutting-edge European research projects. Within the CORBEL Use Cases, EuBI, INSTRUCT, ISBE and ELIXIR for example provide their services to advanced researches to investigate cellular complexes and macromolecular machines using methods from the nano- to the micrometer scale, including 3D information, super-resolution microscopy and functional imaging – with data integration as a common activity thread. This will make it possible for Europe’s research infrastructures to open up their services to researchers throughout the scientific community. “CORBEL provides us with the unique and timely opportunity to continue our work on data integration, and extend our efforts to harmonize physical user access across these essential research infrastructures,” says EMBL Senior Scientist Jan Ellenberg. “This will open a new dimension of opportunities for cutting-edge research in Europe.”


Brief biography:

Jan Ellenberg is Senior Scientist and Head of the Cell Biology & Biophysics Unit at the European Molecular Biology Laboratory (EMBL) in Heidelberg. For over 20 years, he has been interested in cell division and nuclear organization, including systematic analysis of mitosis, nuclear pore complex structure and assembly, as well as chromatin organization and formation and segregation of mitotic and meioticchromosomes.
His goal has been to obtain structural and functional measures of the required molecular machinery inside cells using quantitative 4D imaging, single molecule spectroscopy, as well as super-resolution microscopy. His research group played a key role in large EU-wide efforts on systems biology of mitosis, microscopy automation as well as unbiased computational image analysis. He has coordinated European efforts to make imaging technologies more accessible to researchers. For his scientific merits within cell biology plus his engagement in the integration of bio sciences he was conferred to honorary doctor of philosophy at the Åbo Akademi University, Turku, Finland in 2016 and was elected as member of the Academia Europaea and the Leopoldina in 2017 and 2018, respectively.


邀请人:陈良怡 教授