Surprising discovery of a chimeric protein that combines both ion pump and ion channel
FRANKFURT. For decades it was assumed that protein channels and protein pumps fulfilled completely different functions and worked independently of each other. Researchers at Goethe University Frankfurt and University Groningen have now elucidated the transport path of a protein complex that combines both mechanisms: it first receives potassium from the channel and then transfers it to the pump, from where it is transported to the cell.
A balanced potassium household is critical for the survival of both people and bacteria. As bacteria are exposed to much greater fluctuations in environmental conditions, the controlled intake of potassium often poses a particular challenge. Since the cell membrane is impenetrable for potassium ions, it has to be translocated through specific membrane transport proteins.
On the one hand, potassium channels enable the rapid, but passive influx of potassium ions. This stops as soon as an electrochemical equilibrium between the cell and its environment has been reached. To attain intracellular concentrations beyond this, potassium is transported into the cell actively through potassium pumps, with energy being consumed in the form of ATP.
Since both protein families – channels and pumps – carry out very different functions, they have always been described as separate from each other. This, however, is contradicted by the observation that KdpFABC, a highly affine, active potassium uptake system of bacteria, does not represent a simple pump, but is constructed of a total of four different proteins. One of these is derived from a typical pump, while another one resembles a potassium channel.
Inga Hänelt, Assistant Professor for biochemistry at Goethe University, and her colleague Cristina Paulino from University of Groningen, the Netherlands, therefore decided to take a closer look at the membrane protein KdpFABC through the microscope – or, more specifically, the cryo-electron microscope. They were surprised by the result: “All earlier hypotheses were wrong,” states Inga Hänelt. “Although we had all the data in front of us, it took us a while to understand the pathway potassium takes through the complex into the cell.”
First, a channel-like protein binds the potassium and transports it through the first tunnel to the pump. Once it has arrived, the first, outward-facing tunnel closes, while a second, inward-facing tunnel opens. This tunnel also extends between both proteins and ultimately ends in the interior of the cell. “The complex essentially combines the best qualities of both protein families,” explains Charlott Stock, doctoral candidate in Inge Hänelt’s research group. “The channel-like protein binds potassium, at first very specifically and with high affinity, while the pump enables an active transport that can enrich potassium in the cell by 10,000-fold.”
The data, recently published in Nature Communications, impressed the scientists with how diverse transport through membranes can be. “We have learned that when investigating various membrane transport proteins, we shouldn’t rely on seemingly incontrovertible mechanisms, but have to be ready for surprises,” summarises Inga Hänelt.
Publication:Charlott Stock, Lisa Hielkema, Igor Tascon, Dorith Wunnicke, Gert T. Oostergetel, Mikel Azkargorta, Cristina Paulino, Inga Hänelt, Cryo-EM structures of KdpFABC suggest a K+ transport mechanism via two inter-subunit half-channels, in: Nature Communications, 10.1038/s41467-018-07319-2
An image may be downloaded at: www.uni-frankfurt.de/75137139
Caption: Outward and inward opening structures of KdpFABC in the cell membrane. Credit: Inga Hänelt research group.
Further information: Dr. Inga Hänelt, Institute for Biochemistry, Faculty 14, Riedberg Campus, Telephone: +49 69 798-29262, firstname.lastname@example.org
Friedrich Merz Visiting Professor Donald Ingber cultivates miniature organs on microchips
FRANKFURT. How predictive are animal models for the human body? Which human organs can be recreated in vitro? How can personalized medicine benefit from patient-specific organ systems in the future? These questions are the focus of this year’s Friedrich Merz Visiting Fellowship Endowment with Donald Ingber, who will visit Goethe University from Harvard University for one week at the beginning of December. Ingber develops miniature, living organ systems of human cells for investigating diseases and testing new therapies.
The bioengineering expert developed methods for engineering living human cells on microchips as miniature, three-dimensional organs. These models often deliver more precise results than animal tests, whose predictability for the human body is limited. In addition, they represent a trendsetting option for testing novel drug substances in the laboratory. In cancer therapy, patient-specific tumor cells are cultivated in vitro in order to find a personalized and effective treatment of the individual cancerous disease.
Professor Ingber and Professor Maike Windbergs, who investigates alternatives to animal testing at Goethe University, will present these fascinating new approaches in a clear and understandable way using film material and examples from research and clinical practice in a podium discussion for the general public.
Podium discussion: Human organs and diseases in vitro – fiction or realistic alternative to animal testing?
When: 6th December (Thursday) at 6:00 pm
Where: the Arkadensaal at Goethe House, Großer Hirschgraben 23-25, 60311 Frankfurt.
Additional podium guests include State Animal Welfare Officer for Hessen Dr. Madeleine Martin and Merz Chief Scientific Officer Dr. Stefan Albrecht. Merz is among the pioneers in the development of in vitro tests for Botolinum toxin.
In a symposium on Wednesday 5th December, international experts will discuss “Modelling health and diseases; form in vitro design to future therapies” (Location: Biozentrum, Riedberg Campus, Hörsaal B1, 9 am – 5 pm). The experts include Professor Andries von der Meer from the Twente University in Enschede, Netherlands. He designs artificial blood vessels on chips and uses them to replicate the process of thrombosis. Professor Ernst Reichmann from the Children’s Clinic in Zurich will present clinical studies on the development of artificial skins for burn victims. The presentation by Professor Stefan Hippenstiel from the Charité in Berlin will discuss the use of human lung tissue to simulate infections in the lung.
Goethe University will be represented by the following experts: Professor Florian Greten, Speaker of the Frankfurt Cancer Institute, who will talk about the use of test systems with human cancer cells for preclinical substance tests and in personalized medicine. Dr. Manuel Kaulich from the Institute for Biochemistry II will report on how he uses the gene scissors CRISPR/Cas for the large-scale screening of substances in order to counter resistances in cancer treatment. Professor Ernst Stelzer from the Buchmann Institute for Molecular Life Sciences at Goethe University and his research group investigates spheroids based on pancreatic cells to test new therapies for type I diabetes. For the first time, three young postdoctoral students in pharmacy and medicine will introduce their work in brief presentations.
Donald Ingber will also give a lecture for students on 6th December at 10:00 am on the same topics (location: Otter-Stern-Centre, Riedberg Campus, HS 3). It will be followed by a one-hour discussion with questions prepared by pharmacy students in their 8th semester.
Professor Donald Ingber is founding director of the Wyss Institute for Biologically Inspired Engineering at Harvard University. Tissue engineering is just one of his many areas of research, which also encompass mechanobiology, tumor angiogenesis, systems biology and nanobiotechnology and translational medicine. He has received numerous awards for his creative ideas. In 2015, the journal “Foreign Policy” elected him as “Leading Global Thinker” and his “Organ-on-the-Chip” technology was awarded “Design of the Year” by the London Design Museum. Ingber holds 150 patents and has founded five companies.
Members of the press will have the opportunity to interview Donald Ingber and other experts on the day of the symposium (5th December). Please contact Professor Maike Windbergs for scheduling: +49 (0) 69 798-42715, email@example.com .
Further information: Professor Maike Windbergs, Institut für Pharmazeutische Technologie, Faculty 14, Riedberg Campus, Tel.: +49 (0) 69 798-42715, firstname.lastname@example.org.
Successful cooperation between De Gruyter, the FID Jewish Studies (Specialized Information Services Program) and Knowledge Unlatched Frankfurt/Berlin
FRANKFURT/BERLIN. The Fachinformationsdienst (FID) Jewish Studies and De Gruyter present 20 titles from the field of Jewish Studies Open Access. The e-books have been made openly accessible through Knowledge Unlatched and its "KU Reverse" model. The title list contains important works from the fields of history, Jewish studies and literature, including fundamental works such as the "Handbuch der deutsch-jüdischen Literatur" (Handbook of German-Jewish Literature) edited by Hans Otto Horch and "Die Sprache der Judenfeindschaft im 21. Jahrhundert" (The Language of Antisemitism in the 21st Century) by Monika Schwarz-Friesel and Jehuda Reinharz. The titles can be accessed on Open Access portals such as OAPEN and library catalogues. Together with other freely accessible ebooks, the 20 titles can be found on the publisher's website.
The FID Jewish Studies at the JCS University Library Frankfurt/Main is directed by Dr. Rachel Heuberger and has replaced the former special collections "Science of the Jews" and "Israel". The aim is to provide the specialist community with research-relevant literature, but also to develop innovative research tools. "The free provision of these titles was particularly important to us, as they are used by our scientists in cooperation with other institutions all over the world. The acquisition barrier has previously made academic work more difficult," says Dr. Rachel Heuberger, head of FID Jewish Studies at Frankfurt University Library.
"The cooperation with FID Jewish Studies is a promising start for us to further expand Open Access in this programme segment. We look forward to continuing to work constructively on new models in future in dialogue with our partners in order to promote the idea of free accessibility and easy retrieval of scientific results," says Martin Rethmeier, Editorial Director History at De Gruyter.
FID Jewish Studies: Dr. Rachel Heuberger Head of FID Jewish Studies Phone: +49 69 798 39665 email@example.com www.jewishstudies.de
De Gruyter Eric Merkel-Sobotta Communications Phone: +49 30 260 05 304 mailto:firstname.lastname@example.org www.degruyter.com
Knowledge Unlatched: Philipp Hess Phone: +49 176 239 230 94 email@example.com; www.knowledgeunlatched.org
FID Jewish Studies: The Fachinformationsdienst Jüdische Studien der Frankfurter Universitätsbibliothek (Jewish Studies Special Information Service of the Frankfurt University Library) provides subject-specific information as well as electronic and printed resources for science and research. The search portal (www.jewishstudies.de) offers central access to the entire spectrum of Jewish Studies / Israel Studies and thus enables optimal research.
De Gruyter: De Gruyter has been publishing first-class scientific works for over 260 years. The international publishing house is headquartered in Berlin and has further offices in Boston, Beijing, Basel, Warsaw, Vienna and Munich. De Gruyter publishes over 1,300 new book titles and more than 900 journals annually in the humanities, social sciences, medicine, mathematics, technology, computer sciences, natural sciences and law, and also offers a wide range of digital media. The publishing group includes the imprints De Gruyter Akademie Forschung, Birkhäuser, De Gruyter Mouton, De Gruyter Oldenbourg, De Gruyter Saur, De|G Press, Deutscher Kunstverlag (DKV), Düsseldorf University Press and the publishing service provider Sciendo. For further information, please visit: www.degruyter.com.
Knowledge Unlatched: Knowledge Unlatched (KU) is committed to free access to academic content for readers around the world. The KU online platform serves as a central point of contact for libraries worldwide to support Open Access models, publication collections of leading publishing houses, and new Open Access initiatives. For more information, please visit: http://www.knowledgeunlatched.
The cosmochemist Professor Alexander Krot (University of Hawaii) is coming to Goethe University as recipient of the Humboldt Research Award
FRANKFURT. The observatory on Mauna Kea in Hawaii is world-famous. Less well-known is the fact that the Hawaiian Islands are home to one of the leading institutes for cosmochemistry, the Institute for Geophysics and Planetology (HIGP). One of its scientists is the renowned cosmochemist Professor Alexander Krot, and he is now coming to Goethe University for half a year as Humboldt researcher.
Professor Frank Brenker, geophysicist at Goethe University has been working successfully with Professor Alexandor Kort for years. This gave Krot the impetus to temporarily take leave from his Institute for Geophyscis and Planetology (HIGP) on Hawaii, where a large number of powerful measuring instruments are at his disposal for the examination of extraterrestrial material. As recipient of the Humboldt Research Award he will be working in Frankfurt am Main for six months.
At the Institute for Geosciences at Goethe University, Krot will be working both in teaching and research. He is especially interested in nanoscale analytical methods using transmission electron microscopy and synchrotron radiation, an area in which Frank Brenker specializes.
Alexander Krot made a particular name for himself through his work on the formation of the first solid bodies of our solar system. Numerous fundamental insights into the childhood of the solar nebula are based on his research. With more than 160 publications, of which 14 are in “Nature” or “Science”, his scientific body of work is impressive.
Krot is not only one of the most influential and successful researchers in the area of cosmochemistry, the science of the formation and distribution of chemical elements and compounds in the solar system – he is also an excellent teacher. He can now pass on his knowledge directly in several bachelor and master projects at the same time. “It’s a unique opportunity for our students to be able to work with such an internationally successful researcher this early in their careers,” reports Brenker with pleasure. “Some of them are already familiar with Mr. Krot from his many groundbreaking publications, and it is naturally exciting for them to now be able to discuss things directly with him.”
Images to download can be found at: http://www.uni-frankfurt.de/74667310
Image1: Prof. Dr. Alexander Krot (Copyright: Krot)
Image 2: Off-colour image with magnesium in red, calcium in green, and aluminum in blue. This colour selection was introduced by Alexander Krot for an optimal depiction of the early formations in the solar system. Pictured here is a calcium-aluminum-rich inclusion in the meteorite Efremovka. CAIs are the oldest solid body formation in our solar system. They are 4.567 billion years old, the same age as our solar system. (Copyright: Krot)
Image 3: An artist’s depiction of the solar nebula. (Copyright: NASA/JPL)
Further information: Professor Frank Brenker, Institute for Geosciences, Mineralogy, Riedberg Campus, Tel.: +49(0)69 798-40134, firstname.lastname@example.org
Cancer researcher Dr. Sjoerd van Wijk receives € 222,500 from the German Research Foundation
FRANKFURT. Whether defective cells in the body will live or die is determined by a sophisticated control system. Death receptors play important roles in this system and translate information from outside the cell into critical cellular responses, which are often deregulated in diseases like cancer and inflammation. Cancer researcher Dr. Sjoerd van Wijk from Goethe University will investigate how these receptors function at the molecular level in a new research project which will receive €222,500 in funding over the next three years from the German Research Foundation (DFG).
An effective regulation of programmed cell death is crucial for the correct development of embryos, a working innate immune system, and the prevention of cancer. How cells control the switch between cell survival and death, and which signalling pathways are involved, remain unclear. Proteins that interact with death receptors in these signalling pathways are often marked with various forms of ubiquitin chains, such as linear (M1) and K63-linked polyubiquitin chains. Deubiquitinating enzymes, which specifically break down ubiquitin chains, play a central role in the regulation of these chains, death receptor signalling, and cell fate.
“In our project, we want to investigate the network of M1-deubiquitinating enzymes and interactions with death receptor signalling in mammalian cells in order to understand the fundamental role of the ubiquitin in cell death or survival,” explains Sjoerd van Wijk, group leader at the Institute of Experimental Cancer Research in Pediatrics. The ultimate goal is to understand human diseases, in particular how cancer develops and spreads, and how cells protect themselves against invasive bacteria.
In his research group, van Wijk pursues multidisciplinary approaches using state-of-the-art technology. Through collaborations with Dr. Manuel Kaulich (CRISPR/Cas9 Screening Centre at Goethe University), he has access to highly efficient screening methods to unravel the molecular events that control death receptor function. The analysis of these molecular complexes is also being supported by the ubiquitin mass spectrometry at the Institute for Biochemistry II at Goethe University (Prof. Dr. Ivan Dikic) and at the Institute of Molecular Biology in Mainz (Dr. Petra Beli), as well as by the high-resolution microscopy at the Institute of Physical and Theoretical Chemistry at Goethe University (Prof. Dr. Mike Heilemann).
An image may be downloaded at: http://www.uni-frankfurt.de/74652845
Credit: Dr. Sjoerd van Wijk
Further information: Dr. Sjoerd van Wijk, Institute for Experimental Cancer Research in Pediatrics, Faculty of Medicine, Niederrad Campus, Tel. +49 69 67866574, Email: email@example.com.