Macromolecular Complexes Cluster of Excellence
| State: | Hesse |
| Website: | [1] |
The Cluster of Excellence Frankfurt Macromolecular Complexes (CEF) was an interdisciplinary research center of the Johann Wolfgang Goethe University Frankfurt am Main in cooperation with the Max Planck Institute for Biophysics and the Max Planck Institute for Brain Research . The cluster of excellence was founded in November 2006 as part of the federal and state excellence initiative and funded by the DFG until October 2019.
aims
Macromolecular complexes play a prominent role in fundamental life processes. Due to their fragility, size and low availability, the molecular structure and mechanisms of action of only a few of these complexes are known so far . The cluster contributed to a better understanding of macromolecular complexes. The focus was on structure elucidation , the molecular mechanisms and functions that underlie the interactions between the biological macromolecules in the cell and in the cell membrane . The cluster was committed to scientific excellence and early independence of young researchers and was an internationally known research center in the field of life sciences .
Research areas
The cluster was dedicated to studying all aspects of large macromolecular complexes with the aim of understanding their function. Research at the CEF focused on the following five research areas:
Membrane protein complexes
Biological membranes are central to life. They surround the cells and organelles and separate the internal milieu of the cell or organelle from the external milieu. The basic building blocks of the biological membrane are, on the one hand, lipids , which are arranged in a double layer, and, on the other hand, membrane proteins , which are embedded in the double lipid layer. Sometimes sugar molecules are added, which in turn are bound to the lipids and membrane proteins. Essential basic functions of the cell, such as energy production, food intake, waste disposal and processing of external signals, take place on the biological membrane. In order to be able to perform these diverse functions, most membrane proteins are assembled there to form large and often dynamic protein complexes . The detailed study of membrane protein complexes assumes that these complexes are first removed from their lipid environment. This makes them accessible for structural and functional investigations. Knowledge of the exact structural three-dimensional structure enables the molecular mechanisms to be clarified and the function to be understood in detail.
Quality control and signal transmission
The life of a cell is based on a large number of complex chemical reactions which , taken together, ensure the cell's energy supply, its integrity and stability, as well as its communication with other cells and cell-specific functions. The necessary high precision in the processes of a cell is achieved through the formation of large complexes consisting of many different proteins and / or other biological macromolecules . On the one hand, these complexes ensure that the various reaction centers are close enough to one another so that the product of one enzyme can be processed further by the next enzyme as quickly and efficiently as possible. On the other hand, there are regulatory factors in the complexes that either suppress certain activities or enable them in the first place. The investigation of the regulatory functions in complexes that exist within the cell is one of the central research areas of the CEF. A major difficulty in the investigation of these complexes is that many important regulatory interactions between different components take place via complexes that cannot be isolated in a stable form, i.e. are of a transient nature. However, other interactions are so strong that the components cannot be examined individually. A multitude of biochemical, cell biological and biophysical methods are necessary for the investigation of such a wide spectrum of interactions, many of which are established in the various working groups involved in the CEF. A particular research focus in the characterization of protein-protein interactions was on the investigation of so-called post - translational modifications . Research at the CEF was devoted to the functional and structural biological elucidation of the mechanisms of such post-translational modifications. The researchers at the CEF focused in particular on the most important components of quality control, intracellular signal transmission and transcription .
Dynamics of RNA-Protein Complexes
In addition to translating the genetic code into the amino acid sequence of the proteins, ribonucleic acids (RNA) fulfill many other vital functions in the cell. The discovery of various types of non-coding and regulating RNA elements showed that RNA is not only a passive carrier of information, but that it intervenes very strongly in cellular processes. In order to decipher these interactions and dynamics, the structure and function of these RNA elements must be understood. Members of the CEF succeeded in determining the structural dynamics of several such RNA elements. Using LILBID mass spectrometry and nuclear magnetic resonance spectroscopy , for example, the composition and structure of the HIV TAR RNA ligand complex was analyzed and the complexity of the peptide binding sites of the RNAs was described. Another example is the analysis of the flexibility of RNAs with the help of the electron spin resonance spectroscopy method PELDOR after base-specific spin labeling . As a rule, RNAs do not occur in isolation, but rather as complexes with various proteins. These ribonucleic acid-protein complexes , called RNPs for short, fulfill a wide range of essential functions in the cell. CEF researchers are investigating the highly complex and fascinating interactions between RNA and proteins, the resulting modifications and how quality control works. Many functions of RNPs and the distribution of RNA within the cell are controlled by RNA elements about which little is known.
Protein design
The key positions that macromolecular complexes occupy in the metabolism of every organism include energy generation, the development of cell structures and the regulation or coordination of cellular processes. Selected protein complexes have been specifically modified by CEF members to ensure new functions. Based on the findings from previous research projects, tailor-made macromolecular complexes are intended to perform new tasks and work in a controllable manner. A specific focus of work is the control of cellular processes through light - e.g. B. to drive ion currents through membranes by light. Light-driven ion channels , which primarily conduct sodium and calcium , could be functionally linked with other potassium-conducting ion channels in order to enable new applications in optogenetics . Another focus of the work was to modify protein complexes in the course of a protein design that are naturally responsible for the production of pharmaceutically relevant substances. In this way, nature's synthetic processes can be used to manufacture new drugs, for example to actively counteract the increase in resistance to antibiotics.
Analysis of macromolecular complexes
The challenges presented in the first four research areas required a combined use of established and newly developed physical techniques. CEF aimed to integrate and further develop methods with different energetic, temporal and spatial resolutions. Close cooperation between many different disciplines in the natural and life sciences was necessary. The range of methods used and further developed at the CEF to investigate macromolecular complexes included electron microscopy, X-ray crystallography , electron spin resonance (EPR), proton spin resonance (NMR), fluorescence microscopy and mass spectrometry.
organization
The cluster was chaired by the CEF Assembly, which was composed of Principal Investigators , Adjunct Investigators , Senior Investigators and Associated Members . The CEF Assembly coordinated the research and elected the speaker and board of directors. The spokesman coordinated the cluster and was responsible for budgeting, personnel and investments.
Speaker of the CEF since its inception:
| Volker Dötsch | March 2013 - October 2019 |
| Harald Schwalbe | February 2009 - February 2013 |
| Werner Müller-Esterl | November 2006 - January 2009 |
The CEF administration consisted of the spokesman, the board of directors and the office. An international scientific advisory board composed of six highly respected scientists from relevant research areas monitored the progress of the research and advised the cluster.
Buchmann Institute for Molecular Life Sciences
CEF founded an interdisciplinary research institute on the Riedberg campus of the Goethe University in Frankfurt am Main. The "Buchmann Institute for Molecular Life Sciences" (BMLS) is located in the immediate vicinity of the natural science departments of the university and the Max Planck Institutes for Biophysics and Brain Research. Half of the construction was carried out by the state of Hesse and half by the federal government. It houses research groups from the disciplines of biology, biochemistry, chemistry, physics and medicine.