From The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH): “When dangerous toxins teach fundamental biology”
10.13.22
Nik Papageorgiou
Exploring the mechanics of anthrax infection, scientists at EPFL have discovered two proteins that are involved in controlling the levels of cholesterol in the membrane of our cells.
“What our work shows is how a complex in the center of the cell, the ER-Golgi interaction region, controls plasma membrane cholesterol, which is essential for many cellular functions, if not essential for multicellular life,” says Professor Gisou van der Goot at EPFL’s School of Life Sciences. Her group, working with the group of Giovanni D’Angelo at EPFL, have published a study uncovering how pathogens exploit a key cellular process to intoxicate cells.
Since pathogens have evolved to hijack many of their hosts’ cellular processes, studying host-pathogen interactions help us better understand fundamental biological processes. Here, the scientists found that the interaction between two key organelles in the cell, the endoplasmic reticulum and the Golgi apparatus, is essential to control which lipids are at the cell membrane. Both organelles play essential roles in synthesizing new proteins and their transport within the cell.
The researchers set out to find which proteins are important for the toxin from the anthrax bacterium Bacillus anthracis to enter the cell. To do this, they screened a library of 1500 genes that are normally involved in organizing the cell’s organelles as well as its membrane.
Anthrax infection and ER-Golgi contact sites
The anthrax toxin is made up of three subunits, a Protective Antigen that allows it to bind receptors on the target cell, and two enzymatic subunits, the lethal factor and the edema factor, which are what actually cause damage to the cell.
When secreted, the Protective Antigen binds two receptors on the cell’s membrane. It is then cut up by Furin, an enzyme, and finally associates with other Protective Antigens to form a pore. This pore allows the lethal and edema factors to enter the cell, where they wreak havoc. Although this process is fairly well mapped out, we don’t know which molecules within the cell facilitate all its steps.
From anthrax to biological discovery
The data from the screened genes landed on two genes and their proteins, called TMED2 and TMED10, both of which are located at the ER-Golgi contact sites, a very unexpected location when studying a toxin that comes from the outside of the cell.
When the scientists downregulated the genes of TMED2 and TMED10, the anthrax toxin lost its ability to form pores. Further, in-depth analysis uncovered something new in terms of basic cell biology: that the two proteins organize large protein supercomplexes at ER-Golgi membrane contact sites, which are responsible for the transfer of cholesterol between the two organelles. If this transfer does not occur, cholesterol never gets to the membrane of the cell, and is instead stored in fat droplets.
“Overall, this study of anthrax intoxication led to the discovery that lipid compositional remodeling at ER-Golgi interfaces fully controls the formation of functional membrane nanodomains at the cell surface,” conclude the study’s authors.
Science paper:
Developmental Cell
See the science paper for detailed material with images. A .pdf version is available.
See the full article here .
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The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne] (CH) is a research institute and university in Lausanne, Switzerland, that specializes in natural sciences and engineering. It is one of the two Swiss Federal Institutes of Technology, and it has three main missions: education, research and technology transfer.
The QS World University Rankings ranks EPFL(CH) 14th in the world across all fields in their 2020/2021 ranking, whereas Times Higher Education World University Rankings ranks EPFL(CH) as the world’s 19th best school for Engineering and Technology in 2020.
EPFL(CH) is located in the French-speaking part of Switzerland; the sister institution in the German-speaking part of Switzerland is The Swiss Federal Institute of Technology ETH Zürich [Eidgenössische Technische Hochschule Zürich] (CH). Associated with several specialized research institutes, the two universities form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles Polytechniques Fédérales] (CH) which is directly dependent on the Federal Department of Economic Affairs, Education and Research. In connection with research and teaching activities, EPFL(CH) operates a nuclear reactor CROCUS; a Tokamak Fusion reactor; a Blue Gene/Q Supercomputer; and P3 bio-hazard facilities.
ETH Zürich, EPFL (Swiss Federal Institute of Technology in Lausanne) [École Polytechnique Fédérale de Lausanne](CH), and four associated research institutes form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles polytechniques fédérales] (CH) with the aim of collaborating on scientific projects.
The roots of modern-day EPFL(CH) can be traced back to the foundation of a private school under the name École Spéciale de Lausanne in 1853 at the initiative of Lois Rivier, a graduate of the École Centrale Paris (FR) and John Gay the then professor and rector of the Académie de Lausanne. At its inception it had only 11 students and the offices were located at Rue du Valentin in Lausanne. In 1869, it became the technical department of the public Académie de Lausanne. When the Académie was reorganized and acquired the status of a university in 1890, the technical faculty changed its name to École d’Ingénieurs de l’Université de Lausanne. In 1946, it was renamed the École polytechnique de l’Université de Lausanne (EPUL). In 1969, the EPUL was separated from the rest of the University of Lausanne and became a federal institute under its current name. EPFL(CH), like ETH Zürich (CH), is thus directly controlled by the Swiss federal government. In contrast, all other universities in Switzerland are controlled by their respective cantonal governments. Following the nomination of Patrick Aebischer as president in 2000, EPFL(CH) has started to develop into the field of life sciences. It absorbed the Swiss Institute for Experimental Cancer Research (ISREC) in 2008.
In 1946, there were 360 students. In 1969, EPFL(CH) had 1,400 students and 55 professors. In the past two decades the university has grown rapidly and as of 2012 roughly 14,000 people study or work on campus, about 9,300 of these being Bachelor, Master or PhD students. The environment at modern day EPFL(CH) is highly international with the school attracting students and researchers from all over the world. More than 125 countries are represented on the campus and the university has two official languages, French and English.
Organization
EPFL is organized into eight schools, themselves formed of institutes that group research units (laboratories or chairs) around common themes:
School of Basic Sciences
Institute of Mathematics
Institute of Chemical Sciences and Engineering
Institute of Physics
European Centre of Atomic and Molecular Computations
Bernoulli Center
Biomedical Imaging Research Center
Interdisciplinary Center for Electron Microscopy
MPG-EPFL Centre for Molecular Nanosciences and Technology
Swiss Plasma Center
Laboratory of Astrophysics
School of Engineering
Institute of Electrical Engineering
Institute of Mechanical Engineering
Institute of Materials
Institute of Microengineering
Institute of Bioengineering
School of Architecture, Civil and Environmental Engineering
Institute of Architecture
Civil Engineering Institute
Institute of Urban and Regional Sciences
Environmental Engineering Institute
School of Computer and Communication Sciences
Algorithms & Theoretical Computer Science
Artificial Intelligence & Machine Learning
Computational Biology
Computer Architecture & Integrated Systems
Data Management & Information Retrieval
Graphics & Vision
Human-Computer Interaction
Information & Communication Theory
Networking
Programming Languages & Formal Methods
Security & Cryptography
Signal & Image Processing
Systems
School of Life Sciences
Bachelor-Master Teaching Section in Life Sciences and Technologies
Brain Mind Institute
Institute of Bioengineering
Swiss Institute for Experimental Cancer Research
Global Health Institute
Ten Technology Platforms & Core Facilities (PTECH)
Center for Phenogenomics
NCCR Synaptic Bases of Mental Diseases
College of Management of Technology
Swiss Finance Institute at EPFL
Section of Management of Technology and Entrepreneurship
Institute of Technology and Public Policy
Institute of Management of Technology and Entrepreneurship
Section of Financial Engineering
College of Humanities
Human and social sciences teaching program
EPFL Middle East
Section of Energy Management and Sustainability
In addition to the eight schools there are seven closely related institutions
Swiss Cancer Centre
Center for Biomedical Imaging (CIBM)
Centre for Advanced Modelling Science (CADMOS)
École Cantonale d’art de Lausanne (ECAL)
Campus Biotech
Wyss Center for Bio- and Neuro-engineering
Swiss National Supercomputing Centre
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