Chemistry

Research

A particular highlight in the field of biomedical chemical research is the successful acquisition of the Collaborative Research Centre “Supra­molecular Chemistry on Proteins” (SFB 1093, Speaker Prof. Thomas Schrader, Vice Speaker Prof. Carsten Schmuck), which is receiving around seven million euros in funding from the DFG over a four-year period. Since April 2014, 14 research groups from Chemistry, Biology and Medicine at our University have been working together in this centre on developing chemical molecules that can modulate the biological ­properties of proteins. They are supported in their work by two research groups from the Max Planck Institute for Physiological Chemistry in Dortmund. Proteins are the tools of the cell. There are numerous biological or medical processes in which proteins are involved. As enzymes they ­selectively accelerate chemical reactions, e. g. in metabolic processes, and as receptors they mediate signals sent to a cell from outside. In this way they control when a gene is activated or a cell divides or is sent to controlled cell death. The often highly complex interaction between the proteins and their partners, which may be other proteins, nucleic acids or hormones, has previously not been understood fully at molecular level. This marks the starting point for the Collaborative Research Centre (SFB). The scientists collaborating in this group are developing molecules that are tailored to specifically interact with individual proteins and in doing so selectively modify the biological function of that protein. This essential work makes it possible not only to learn more about these fundamentally important processes; it could also lead to the development of new active substances, since a malfunctioning protein is often (co-)responsible for triggering diseases. The chemists employ a large array of very different methods in this work. Beginning with known ­biologically effective natural substances, they make specific modifications that enable the ­molecules to also bind to proteins with which they have not previously interacted. In another approach, polymers are fabricated with specific adhesive groups that can bind to complementary binding sites on a protein surface. These polymers can bind on entire edges and side faces of a protein like a molecular net, thus preventing another protein from docking onto the same site. In other work, the scientists are generating specific ­mixtures of several hundreds of very similar molecules (known as combinatorial libraries), from which the molecules having the required properties (e.g. binding to a specific protein) can be identified by a special selection process. Once chemical molecules with interesting properties have been thus found, the participating biologists investigate them for their biological properties. This is done using methods ranging from testing the reactions of the isolated proteins in the test tube and cell-based studies to animal experiments in cooperation with Medicine. The latest structural examination techniques (e. g. NMR, x-ray crystallography and Raman spectroscopy) are used in combination with theoretical calculations to analyse the observed effects at molecular level. With these findings as a basis, it is then possible to move on to developing the molecules further and tailoring them more specifically to the given protein.

The SFB may only just have got underway, but the participating research groups have already produced their first very promising results. For example, it has been possible to intensify interaction between two proteins using a small triarmed molecule, which acts as a kind of chemical adhesive to bind the two proteins together. Specifically ­influencing such protein-protein interactions under physiological conditions with a tiny molecule has only succeeded in a very small number of cases worldwide. In another area of their work, the researchers showed how molecular tweezers, which can bind to positively charged residues on the surface or in a groove of a protein, can switch off various enzymes that are involved in intestinal damage. Interestingly, similar molecular clips can also be used to prevent the formation of protein deposits, known as plaques. These ­deposits occur in the brain, for example, in neurodegenerative diseases such as Alzheimer and ­adversely affect nerve cell function. The chemical clips developed by the chemists in Essen prevent formation of such plaques by binding on the ­proteins at special sites that are important for binding between the proteins. The first tests on Alzheimer rats proved very promising, showing an actual improvement in the rats’ cognitive abilities. Nevertheless, there is still undoubtedly a long way to go between such fundamental research and possible drug development.

Research at the Faculty of Chemistry is not only on proteins, however, but also on genes. Here our chemists cooperate with partners from Biology and Medicine to develop chemical transport systems that introduce genes into cells. ­Nucleic acids, the carriers of genetic information, are not able to enter a cell from the outside on their own. However, this is precisely what is required in gene therapy, which attempts to replace malfunctioning genes inside a cell with a functioning gene from outside. To do this, transport systems – known as transfection vectors – are needed to bind the DNA and transport it through the cell membrane into the cell. The chemists from our Faculty have two successful but very different ways of doing this: in one approach, nanoparticles made of calcium phosphate or noble metals such as ­silver or gold are used as the transport vehicle. In the other, small organic molecules are produced which bind specifically to a nucleic acid. The resulting DNA/nanoparticle or DNA/molecule complexes are then delivered into cells. Once ­inside, the DNA is released and can trigger gene production in the cell. Researchers working in conjunction with a group from Biology have ­recently developed the smallest known peptide-based transfection vector. Peptides usually need at least ten or more positively charged amino ­acids for efficient gene transfection to take place. However, if the amino acids are given a tailored chemical adhesive group as developed by our chemists, which can bind specifically both to the DNA as well as to negatively charged groups on the cell surfaces, it takes only four of these artificial amino acids to achieve highly efficient gene transfection – a world record.

Specially functionalised calcium phosphate nanoparticles have been found to protect at least mice against viral infections such as influenza. Researchers in our Faculty have developed biodegradable nanoparticles containing an antigen specific to the influenza virus. The antigens released as the particles degrade have been shown to lead to immunisation in mice. Perhaps such particles will also be used for the flu vaccine in the not-too-distant future?

Research groups from Chemistry and Medicine have long been successfully investigating special nanocapsules which are filled with fluorinated hydrocarbons and can be used as blood substitutes. The fluorinated hydrocarbons inside the capsule, a kind of liquid Teflon, can store and release large amounts of oxygen but are completely immiscible with water. Packed inside the nanocapsules, the oxygen can be distributed normally in the blood and released wherever it is needed. Such artificial oxygen-carriers are especially interesting for treating acute shock in emergency medicine. The scientists are presently working on a special surface coating to extend the length of time the capsules can remain in the body.

Water is at the centre of many research projects in our Faculty. For example, our scientists are developing new methods of detecting minute traces of toxic contamination in water. Biofilms as a source of drinking water contamination and the effects of microorganisms on corrosion ­processes are further key themes. Other work looks at microorganisms that live under unusual conditions, such as Archaea, which thrive in ­sulphuric acid at temperatures of 80°C. One of our research groups has recently discovered that microorganisms can also live in tiny inclusions of just a few microlitres of water in crude oil. To what extent these microorganisms are capable of causing degradation of the oil in deep reserves is currently being investigated. The Faculty of Chemistry furthermore plays a significant role in the new “Fortschrittskolleg – Future Water” progress group (coordinated by Prof. Torsten Schmidt), which is comparable to a state research training group and is being funded from 1 October 2014 for an initial four-and-a-half years by the State of North Rhine-Westphalia. In the group, twelve doctoral researchers will address highly interdisciplinary issues of urban water research.

The main focus in the Didactics of Chemistry is on empirical educational research. The ­researchers there ask questions such as what makes learning successful, or what role experimentation plays in chemistry lessons or visualisation in learning chemistry. The researchers from our Faculty lead the field nationwide in empirical ­research of this kind and are among a handful of experts in their discipline nationally to also receive DFG funding for their work. This puts them at the top of the nationwide DFG Funding Atlas, well ahead of all the other universities. It was thus possible, following conclusion of the Research Unit and Research Training Group “Teaching and Learning of Science” in 2013, to secure a new DFG collaborative project in virtually seamless ­succession in 2014. In a total of five subprojects in the Didactics of Biology, Chemistry and Physics and in Psychology, the new DFG Research Unit is working with scientists from the various disciplines to investigate the factors affecting “Academic learning and successful study in the initial stages of scientific and technical degrees” (ALSTER). In light of the continuing high dropout rates in these areas, the Research Unit is addressing current educational issues relating to criteria for student success, a topic that has not been investigated systematically to date. The coordinator of the Research Unit is Prof. Elke Sumfleth from the Didactics of Chemistry.