Volker Dötsch elected to EMBO membership
20th October 2011 - The FMLS Vice Director and Professor at the Institute of Biophysical Chemistry of the Goethe University Frankfurt has been elected by EMBO as one of 46 new members worldwide. By awarding life-long membership, EMBO acknowledges the outstanding scientific contribution of Volker Dötsch and his commitment to research excellence. 1500 scientists are members of EMBO, all of them leaders in their fields.
Volker Dötsch is an expert in structural biology, combining modern methods of structure determination with a range of biochemical techniques and cell biology experiments to decipher the regulation of cellular processes and signal transduction. His group focuses on analysis of antibiotics synthesis in bacteria and fungi, the characterization of membrane proteins, including proteins involved in the plaque formation underlying Alzheimer's disease, and on mechanisms of quality control in the femal germline. For years, Volker Dötsch has been publishing his results in high-ranking journals like Science, Nature, or PNAS.
Completion of FMLS building
August 2011 - After only two years of construction time, the new FMLS building has now been finished. Seven groups from a wide range of disciplines have moved in already, creating a vibrant scientific atmosphere. The building offers excellent conditions for cutting edge research in Life Sciences, bridging the gaps between Physics, Biology, and Chemistry. It houses a first-class Electron Microscopy Facility, a dedicated Crystal Facility, and the Frankfurt Centre for Advanced Light Microscopy (FCAM). Link to webcam.
Guiding tail-anchored membrane proteins to their destination
30th June 2011 – A newly synthesized protein is as fragile as a newborn baby. It could never fold into its correct three dimensional structure if it would not be protected by chaperones. In case of membrane proteins chaperones do not only prevent their aggregation, but also escort them to their destination and aid in membrane insertion. For the so called family of “tail-anchored” (TA) proteins, which are secured in the membrane via a single helix, an interdisciplinary research team now managed to decipher the underlying molecular mechanism by combining X-Ray Crystallography and NMR-Spectroscopy with biochemical and cell-biological studies.
The group of FMLS deputy director Volker Dötsch contributed by showing that the central chaperon of the responsible protein complex, called Get3, regulates both binding to TA proteins within the cytosol and their release at the membrane. The two receptor proteins Get1 and Get2 aid in TA protein insertion. They use overlapping interfaces for the interaction with Get3. On the basis of different crystal structures the researchers suggest a model for the mechanism of how TA proteins are inserted into the membrane. Upon interaction with its membrane receptor the Get3 dimer gradually opens up to allow for the controlled TA protein insertion. “Those results are particularly important because they enabled us to establish the first model of the receptor-assisted membrane insertion of TA proteins that will now be the basis for further studies” comments Dötsch.
New defense mechanism against Salmonella elucidated
26th May 2011 – After infection, Salmonella usually accumulates in contained vacuoles inside cells. However, a small percentage of bacteria escape these compartments and start rapidly replicating in the cytosol, a mechanism which is viewed as important for dissemination of the disease to new hosts. This uncontrolled proliferation in the cytosol can be prevented by an evolutionary conserved process called autophagy. Cytosolic Salmonella are recognized, surrounded by a membrane vesicle and marked for degradation via the lysosome.
An international group of scientists around FMLS director Ivan Dikic has now discovered a new molecular link for this recognition of Salmonella by the autophagy membrane. They showed that the protein Optineurin functions as inducible autophagy receptor which is activated by phosphorylation. It binds to ubiquitinylated Salmonella as well as to the autophagosomal membranes, thereby selectively delivering the Salmonella to the autophagy clearance pathway. It is proposed that the phosphorylation of autophagy receptors represents a general mechanism for the regulation of autophagy processes which are operational e.g. in neurodegenerative disease to remove protein aggregates or in cancer development.
The world’s smallest wedding rings
6th April 2011 - Creating artificial structures from DNA is the objective of DNA nanotechnology. This new discipline makes use of the ability of natural DNA strains to self-assemble. As reported by FMLS scientist Alexander Heckel and his PhD student Thorsten Schmidt in today’s online issue of Nano Letters, they now succeeded in creating two rings of DNA only 18 nanometers in size and to interlock them like two links in a chain. Such a structure is called catenan, a term derived from the Latin word catena (chain). Schmidt, who got married during the time he was working on the nano-rings, believes that they are probably the world’s smallest wedding rings.
From a scientific perspective, the structure is a milestone in the field of DNA nanotechnology, since the two rings of the catenan are not fixed, but can rotate freely under certain conditions. They are therefore suitable as components of molecular machines or of a molecular motor. “We still have a long way to go before DNA structures such as the catenan can be used in everyday items”, says Alexander Heckel, “but in the near future structures of DNA can be used to arrange and study proteins or other molecules that are too small for a direct manipulation.” This way, DNA nano-architectures could become a versatile tool for the nanometer world, to which access is difficult. Link to full article, to German or English press release.
Understanding the development of chronic dermatitis
31st March 2011 - Mice deficient in the protein SHARPIN suffer from chronic proliferative dermatitis, with the underlying pathogenesis being only partly understood. The team around FMLS director Ivan Dikic now discovered a novel role of SHARPIN, which might explain the severe phenotypes observed in mice. The scientists showed that SHARPIN is part of the LUBAC complex and stimulates the formation of linear chains of the ubiquitin protein. These linear ubiquitin chains are attached to the NEMO protein, subsequently triggering activation of NF-κB, a transcription factor with a central role in the regulation of immune responses, cell proliferation and development. Absence of SHARPIN leads to dysregulation of this signalling pathway. In addition, the scientists also showed that SHARPIN works as an inhibitor of apoptosis via a separate signalling pathway. If SHARPIN is not functional, cell death is increased. This is a potential mechanism by which inflammatory skin lesions are formed in SHARPIN deficient mice. Link to full article and German/English press release.
Japan Tsunami Appeal
21st March 2011 - The FMLS & CEF Offices are collecting donations for the Japanese Red Cross Society until the end of March. If you wish to participate in this effort, please visit the office or use the following links to find information of how to donate directly to the Japanese Red Cross or to the German Red Cross.
Fatal quality control in oocytes
18th February 2011 - Maintaining DNA integrity in oocytes is of paramount importance to avoid dissemination of mutations to the next generation. A tight quality control mechanism exists, which leads to sacrificing oocytes rather than risking any damage. This is especially painful for female cancer patients treated with chemotherapy, as chemotherapeutic agents damage the DNA of oocytes, resulting in cell death and, consequently, in infertility. Little has been known about the exact mechanisms triggering cell death; therefore therapeutic approaches to prevent infertility have remained ineffective.
In cooperation with international partners, the group of FMLS scientist Volker Dötsch has now started to unveil the mechanism behind the treatment related infertility. Essential for this process is the protein p63, a member of the p53 protein family which has gained a reputation as “guardian of the genome”. The Dötsch group has now shown how p63 is regulated. In normal oocytes, the level of p63 is high, but the protein is kept in a closed dimeric and inactive state. If DNA is damaged, p63 becomes phosphorylated and the structure of the dimer changes to an open state allowing the attachment of a second phosphorylated dimer. The result is an active p63 tetramer which is capable of initiating cell death of damaged oocytes. Link to full article and German press release.
Directing worms with light
16th January 2011 - FMLS scientist Alexander Gottschalk has shown for the first time how the movement of an animal can be reliably and precisely directed through light impulses. The new technology was published online today in Nature Methods.
The team headed by FMLS scientist Alexander Gottschalk has employed optogenetics to control nervous cell function of the worm C. elegans by light. Optogenetics has recently been chosen as “Method of the Year 2010” by the journal Nature Methods and is an extremely powerful tool to carry out detailed studies on mechanisms of the nervous system. In the few years since its development the technology has revolutionized experimental approaches in neuroscience. The method has great potential for the study of numerous signaling pathways in cell biology. Frankfurt scientists Ernst Bamberg and Alexander Gottschalk are amongst the pioneers in using and further developing this new research tool.
Earlier optogenetic experiments in small organisms have mostly been performed using whole-field illumination and genetic targeting, strategies that do not always provide adequate cellular specificity. Targeted illumination can be a valuable alternative but it has only been shown in motionless animals without the ability to observe behavior output. In collaboration with Hang Lu from the Georgia Institute of Technology, Atlanta, USA, the team around Alexander Gottschalk has now developed a real-time, multimodal illumination technology that allows both tracking and recording the behavior of freely moving C. elegans worms while stimulating specific cells that express channelrhodopsin-2 or inhibiting other cells that express the light-activated proton pump MAC. This new technology enhances the ability to control, alter, observe and investigate how neurons, muscles and circuits ultimately produce behavior in animals using optogenetics. Link to full article or watch video.