Biomedical Science
Research – Selected Highlights in 2012–2013
Research at the ZMB is organized into three programmes, which are introduced in the following chapter with some exemplary projects.
Oncology
Oncological research is one of the top priority areas of the University Hospital Essen. The West German Cancer Centre (WTZ), since 2009 supported by Deutsche Krebshilfe (German Cancer Aid) as one of its Oncology Centers of Excellence, represents the central structure for clinical, translational, and basic cancer research at the Medical Faculty. The WTZ has evolved to become one of the leading Comprehensive Cancer Centers in Europe and is one of seven partner sites of the German Cancer Consortium (DKTK), which together with the German Cancer Research Center (DKFZ), Heidelberg, forms the national network for translational cancer research funded by the BMBF and federal and state governments.
The Department of Medical Oncology, headed by Prof. Martin Schuler, is the largest academic institution fully dedicated to medical oncology in Germany. It comprises four independent research groups and was recently further strengthened by the appointment of Prof. Jens Siveke, who took up the W3 professorship for Translational Oncology with a focus on thoracic and visceral oncology. Before joining the Medical Faculty in Essen, Prof. Siveke conducted many years of basic and translational research on solid tumours at the Technical University of Munich (TUM). Together with a team from the DKTK and international partners, he was able to identify a new epigenetic approach to the treatment of pancreas carcinoma. The findings were published in Nature Medicine in 2015 and commented on in three editorials: Nature Reviews Cancer; Cancer Discovery; Nature Reviews Gastroenterology and Hepatology.
The phase I unit runs one of the strongest programmes in early clinical development, biomarker-stratified precision oncology, and immuno-oncology in Europe. Recent examples of successful precision oncology studies at the WTZ include the LUX-Lung 3 study, which led to the approval of the irreversible pan-ERBB inhibitor Afatinib for the treatment of patients with EGFR-mutated lung cancer. The analysis of the treatment effect of Afatinib on survival on the basis of two phase III studies was published early in 2015 in Lancet Oncology.
The results of another recent biomarker-stratified study with the participation of the WTZ were published in 2015 in the highly renowned New England Journal of Medicine and concerned the targeted treatment of patients with tumours originating from different organs carrying a so-called BRAF V600 mutation. The drug Vemurafenib (Zelboraf®), so far approved in Germany only for the treatment of melanoma patients carrying a BRAF V600 mutation, proved to be effective in different non-melanoma tumours carrying the corresponding mutation (Hyman DM et al. 2015).
The Department of Medical Oncology also contributed to pioneering clinical studies with the immunostimulatory antibody Nivolumab, paving the way to a new therapeutic option for patients with metastasized lung and renal cell carcinoma. Nivolumab is a monoclonal antibody against the PD-1-receptor (programmed cell death 1) on activated T-cells. Blockade of the receptor induces an enhanced T-cell response against the tumour cells. The group of patients treated with immunotherapy had a significantly longer mean survival time compared to patients receiving standard therapy. The results of the study were similarly published in the New England Journal of Medicine in 2015.
The Clinic for Dermatology at the UK Essen is known beyond the region for its highly regarded expertise in the area of skin cancer research. It has been led since 2008 by Prof. Dirk Schadendorf, who has also been acting director of the WTZ since May 2013. The strong international reputation of research in this area is documented by the results of a study of the renowned journal Lab Times in October 2014 evaluating the most often cited scientists in dermatology in Europe. The analysis shows that Prof. Schadendorf is among the most often cited scientists in the field, occupying third place in the ranking. Also in honour of his achievements, Prof. Schadendorf was awarded the valuable Wilhelm-Warner Prize in 2015: “…for his pioneering contributions to experimental research and the therapy of melanoma, which contributed to a considerably improved prognosis for melanoma patients.” Meanwhile, the Fritz-Acker-Foundation’s “Förderpreis 2013” was awarded to Prof. Alexander Roesch, Dermato-Oncology, in 2014, in recognition of his scientific contributions to research of malignant melanoma.
The central interest at the Clinic for Dermatology is experimental and clinical research into the diagnosis, therapy, and resistance to therapy of malignant skin cancer (melanoma). On the basis of molecular pathological data, new tyrosine kinase inhibitors which interfere with the RAS-/RAF-signal transduction pathway were identified and have been developed for the targeted therapy of melanoma. The drugs build on the finding that malignant melanomas carry certain mutations in the tumour, so called BRAF mutations. Clinical phase II studies with the participation of Dermatology in Essen proved a survival benefit for patients treated with Vemurafenib and Dabrafenib, two kinase inhibitors specifically inhibiting kinase activity of mutated BRAF. However, the tumours also develop resistance to the new drugs. Against that background, work has been done on new drugs that interfere with the RAS-/RAF-signal transduction pathway at different positions.
With the tumour inhibitory activity and a survival benefit for Trametinib, an inhibitor of the so-called MEK, having been documented in clinical studies, a combination of the two drugs was now studied clinically on the assumption that it might reduce or delay the occurrence of therapy resistance to the BRAF inhibitor. New multi-centre phase III studies provided evidence in support of this expectation. The combination of Dabrafenib and Trametinib caused a significant prolongation of overall and progression-free time of survival, as well as an improvement in health-related quality of life (HRQoL). The results were published at the end of 2014 and in 2015 in renowned scientific journals such as the New England Journal of Medicine, Lancet and Lancet Oncology.
In addition to research into small molecule inhibitors, Prof. Schadendorf’s group has been contributing successfully for a number of years to the development of new immune therapy approaches. As a first step the group succeeded in demonstrating the efficacy of Ipilimumab, which contains an immune modulatory antibody against CTLA-4 (cytotoxic T-lymphocyte-associated Protein 4). CTLA acts as a brake (immunological checkpoint) on the activation of cytotoxic T-cells, which is released by the antibody. This causes an increased activation of cytotoxic T-lymphocytes and an increased immune response directed against the tumour, but also against healthy cells. The Clinic for Dermatology in Essen participated in the clinical study of new immune modulatory antibodies, Nivolumab und Pembrolizumab, which interfere with the immune system at a different position. They target the PD-1-receptor (programmed cell death 1) on active T-cells. Blockade of the receptor causes increased T-cell activity against the tumour cells. Nivolumab, approved in Germany since mid-2015, was shown in phase III studies in both untreated and pretreated patients with an advanced stage of melanoma to be more effective than chemotherapy. The new drug proved superior also in comparison to Ipilimumab. A further improvement in the therapeutic effect was also indicated for the combination of the two “checkpoint inhibitors”, Ipilimumab and Nivolumab. The enormous progress in the therapy of malignant melanoma to which the group of Prof. Schadendorf has contributed substantially is documented by several publications within the last two years in journals including the New England Journal of Medicine.
A further research highlight of the Clinic for Dermatology (PD Dr. J. Klode, Dr. I. Stoffels and others) and the IMCES (Prof. M. Gunzer and others) is the development and application of a new imaging method jointly developed by the scientists. They were able to demonstrate that metastases in malignant melanoma can be detected reliably in the sentinal lymph nodes without surgery thanks to this new procedure. The results were published at the end of 2015 in the scientific journal Science Translational Medicine.
Genetic studies into possible mechanisms of tumour development in neuroblastoma have been performed by the group of Prof. A. Schramm (Pediatric Clinic III at the UK Essen), who was appointed adjunct professor at the end of 2015 in honour of his achievements in the field of Experimental Oncology. Neuroblastoma accounts for seven to eight percent of all childhood cancers and is the third most frequent form of cancer among children. The genetic studies revealed a new and so far unknown mechanism of tumour cell development. In collaboration with colleagues at the University Hospitals of Cologne, Heidelberg and Berlin, UDE researchers found that the gene for the protein Telomerase is activated in the tumour genome in high-risk neuroblastoma patients. Rearrangements within the tumour genome cause expression of this protein, which in normal cells is not expressed, to be switched on permanently. The self-destruction mechanisms of the affected cells are switched off as a result, causing unlimited cell division and tumour development. These results were published in Nature in October 2015.
Aiming to improve the therapeutic options of relapsed neuroblastoma patients, a multidisciplinary team of researchers headed by the ZMB members Prof. A. Schramm and Prof. J.H. Schulte from the UK Essen initiated an integrated analysis of whole-exome sequencing, mRNA expressions, array-CGH and DNA methylation data, focusing on differences between primary (at diagnosis) and recurrent neuroblastoma cancer patients. The analysis revealed characteristics of evolutionary dynamics in neuroblastoma and new mutational changes in relapse patients. This type of analysis is a promising approach for detecting genetic and epigenetic changes in cancer evolution and opens up new avenues in the treatment of relapse patients. The scientific results were published in Nature Genetics in 2015.
The results of whole-exome sequencing and epigenetic analyses of 200 lymphomas represent a highlight in the work of Prof. Ralf Küpper’s group at the Institute for Cell Biology (Cancer Research). Within the framework of the International Cancer Genome Consortium (ICGC) on B-cell lymphomas, it was proven that Burkitt lymphomas exhibit certain epigenetic changes that complement known genetic lesions and contribute to pathogenesis. The results were published in Nature Genetics.
For the Clinic for Hematology (director Prof. U. Dührsen), the final results of three multicentric clinical studies coordinated in Essen mark the research highlights of 2014/2015. Because of their high clinical and scientific relevance, the results of the three studies (PETAL, EIS, and DECADE) were selected for oral presentation at the annual conference of the American Society of Hematology.
Immunology, Infectious Diseases and Transplantation
The immune system responds to various pathogens including viruses and bacteria in different ways to prevent severe disease and persistence in the host. Many pathogens, however, have developed mechanisms to evade immune defence. The molecular and cellular interactions of pathogens with the immune system are studied by several groups at the ZMB within this programme. The objective is to gain an understanding of the fundamental mechanisms behind these interactions in order to develop strategies for immunotherapy and vaccination. In the field of transplantation, immuno-genetic research and diagnostics are performed in order to prevent rejection.
Key themes in this area are reflected by the objectives of the collaborative research projects mentioned above: CRC/TRR60, the research training group RTG 1949, and the EU-funded international science network Mye-EUNITER. The group of Prof. Gulbins (Institute for Molecular Biology at the UK Essen) is complementing the spectrum of approaches through the framework of FOR 2123 with scientists from the University of Würzburg to investigate the role of sphingolipids during infection of host cells by pathogens, especially bacteria.
The study of molecular and cellular mechanisms of the immune reaction is the focus of work in the group of Prof. K.S. Lang, head of the Institute for Immunology at the UDE. Prof. Lang’s group in cooperation with PD Dr. Bernhard B. Singer (Institute for Anatomy, UK Essen) produced pioneering new findings on the importance of the transmembrane glycoprotein CEACAM1 for the body’s anti-viral defence response. CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) is a cell adhesion protein mediating cell adhesion through homophilic or heterophilic binding to related proteins of the same subgroup. In addition to numerous other functions, CEACAM1 is of crucial importance for the survival of B-lymphocytes, white blood cells. It influences their homeostasis and is essential for the antiviral immune response. If the protein is absent, B-lymphocytes fail to receive the essential signal and the production of antibodies is not triggered. This important finding was published in 2015 in the renowned journal Nature Communications.
New insight into the formation and function of B-lymphocytes as a component of the adaptive immune system was gained in the reporting period by a team of researchers at the UK Essen under Prof. R. Küppers and published in two articles in the Proceedings of the American National Academy of Sciences USA (PNAS). As a pillar of humoral immunity (formation of antibodies) the antibody-producing B-lymphocytes differentiate upon activation to antibody-producing plasma cells or to memory cells. So far the existence and the joint or separate generation of sub-populations of human memory B-cells has been controversial. The new findings indicate that huge memory B-cell clones are formed as part of the immune response and that IgM+ and IgG+ memory B-cells are often formed from mutual progenitor cells, which also confirms that IgM+ B-cells with mutated immunoglobulin genes are in fact memory B-cells.
Important progress with regard to the analysis of neutrophilic granulocytes, key cells of the innate immune response against naturally occurring diverse pathogens, was achieved by a team of scientists at the UDE and UK Essen led by Prof. M. Gunzer, director of the Institute for Experimental Immunology and Imaging, together with scientists from institutes in Magdeburg, Mainz, Erlangen and Bonn. They succeeded in breeding a mouse strain in which neutrophils can be labelled by the expression of a fluorescent protein and an enzyme. The method permits identification and analysis of neutrophils. It is therefore possible for the first time to study functions of neutrophils in living organisms using molecular imaging. The results were published in 2015 in the respected journal Nature Methods.
A new approach to combating bacterial infections is being pursued by a research team led by Prof. E. Gulbins and Dr. K. Becker-Flegler from the Institute for Molecular Biology together with an international group of scientists. What is particular about the approach is that the researchers make use of a common infection mechanism of bacteria. Certain bacteria secrete toxins that integrate into the host cell membrane. In the process they destroy the membrane, which can cause death of the cell. Inspired by this principle, the UDE group in collaboration with scientists from Bern, Liverpool, and Cincinnati (USA) have produced artificial membrane vesicles (liposomes) to absorb the toxins. The scientists found that liposomes are very effective and neutralize bacterial toxins efficiently. The results give reason to hope that liposomes can be used alone or in combination with established antibiotics as an effective therapy with minimal side effects for treating severe infections. These results were published in 2014 in Nature Biotechnology.
Important new findings concerning the evolution of two prokaryotic evolutionary lineages, bacteria and archaea, have been generated by an international study with the participation of Prof. B. Siebers, UDE Faculty of Biology, Department of Molecular Enzyme Technology. The results published early in 2015 in Nature may be highly relevant to a better understanding of the development of antibiotic resistance in hospitals. Cells without a cell nucleus (prokaryotes) are capable of transferring genes across species barriers by horizontal gene transfer during reproduction. The international research consortium studied the evolutionary history of archaea, an ancient group of organisms, using sequence comparison of a high number of their genes with bacterial sequences. The sequence comparison revealed that 39 percent of the archaea genes studied originate from bacteria in the course of evolution. Genetic information provided the archaea with new metabolic capabilities and presumably allowed them to occupy new environmental niches.
Hematopoietic stem cells, transplantation and tumour immunological questions, as well as the translational development of new hematological cell therapies, are at the centre of interest at the UK Essen’s Institute for Transfusion Medicine headed by Prof. Peter Horn. An extraordinary success for the institute was its successful participation in 2014 in the Translational Stem Cell Research competition of the State of North Rhine-Westphalia with total funding of four for million euros. Transfusion Medicine in Essen is involved in two of the seven winning projects.
Molecular and Chemical Cell Biology
The Molecular and Chemical Cell Biology research programme was established in 2014 with the aim of combining up interdisciplinary research expertise and fostering the scientific focus on mechanistic and chemical cell biology to achieve a deep understanding of pathological processes by studying molecular mechanisms at high resolution.
The goals of the research programme reflect those of the Collaborative Research Centres CRC 1093 and CRC/TRR 60, the Research Training Groups RTG 1431, 1739, 1949 and 2098, as well as the DFG priority programmes (see above).
Scientific questions within the programme require a high degree of interdisciplinary collaboration, for which the ZMB offers an optimal structure by joining Biology, Chemistry and Medicine under one roof. In this way, chemistry develops new concepts for the detailed analysis of molecular mechanisms, signal transduction pathways and the functionality of molecular switches by generating specific molecules suitable for acute and selective interference with molecular processes and structures.
Within the reporting period, evidence of a promising new approach to HIV/AIDS therapy has been provided by building on certain supramolecular structures. Scientists from a team led by Prof. Thomas Schrader, Institute for Organic Chemistry, have developed so-called supramolecular tweezers during the past few years which bind specifically to lysine residues at the surface of proteins. In a recent study the scientists were able to show that one of the molecular tweezers binds to the protein SEVI (Semen-derived Enhancer of Virus Infection) in seminal fluid. This protein forms amyloidal structures to which HIV binds. Docking to amyloid is essential for the viral infection process. In addition, the tweezer destroys the viral envelope and causes efflux of the liquid content. The antiviral action based on the dual activity of the tweezer was demonstrated in work with researchers from the USA and University Hospital Ulm and was published in eLife in 2015.
The potential of small bioactive molecules for the analysis of signal transduction pathways has been demonstrated in a joint project between Prof. Markus Kaiser, UDE Chemical Biology, and Dr. Erich Kombrink, Max Planck Institute for Plant Breeding Research in Cologne. The scientists developed a small molecule as a tool to decipher signal transduction networks of the plant hormone Jasmonic acid, which controls multiple pathways in plants. It was possible to find a specific inhibitor of Jasmonic acid. With its help the scientists not only succeeded in dissecting the diverse functions of Jasmonic acid but also in identifying its target. The results were published in Nature Chemical Biology in 2014.
As a result of the collaboration of Prof. Carsten Schmuck, UDE Supramolecular Chemistry, and Prof. Shirley Knauer, UDE Molecular Biology II, a new vector system for artificial gene transfer has been developed. The system is based on the smallest peptidic vector known so far, a tetrapeptide, with a specifically designed analogue of the amino acid arginine in the sidechain. The chemical structure and the characteristics of the arginine analogue lend special transfection properties to the compound. The development work was documented in several publications in the high-ranking scientific journal Angewandte Chemie.
DNA nanotechnology is an emerging and future-oriented discipline and the focus of the Bionanotechnology group headed by Dr. Barbara Sacca, Chemical Biology at the ZMB. Here, different approaches are pursued to build two and three-dimensional DNA objects with precisely defined nanometer-sized features. Because the spatial coordinates of each atom within the DNA nano-objects can easily be predicted on the basis of the double helical structure, the method offers an extraordinary possibility: to organize matter into a desired spatial arrangement, with a precision of just a few nanometers. Indeed, any functionality that can be conjugated with DNA can be placed at a predetermined position of the DNA nanostructure and used as a probe for molecular recognition. Recent research results have been published in the highly regarded scientific journal Angewandte Chemie.
A further area of research in the Sacca group aims at the development of functional DNA-based nano-containers for controlled protein loading. Chemical modification of the inner cavity of such nano-containers with region-selective ligands will allow targeting of selected sites over the protein surface. This in turn may be used to better understand distinct biochemical events and possibly modulate protein properties through their spatial confinement into an engineered microenvironment.
A central task of the Molecular and Chemical Cell Biology programme is the molecular analysis of signal transduction pathways and of protein complexes acting as molecular switches at decision points of signal transduction processes. One main focus concerns signalling in cell proliferation and regulation of cell cycle control.
The group of ZMB member and UDE honorary professor Andrea Musacchio at the MPI for Molecular Physiology in Dortmund studies the molecular mechanisms of chromosome segregation. The focus is on large macromolecular assemblies called kinetochores, which are composed of at least 30 core subunits. Their primary function is to create physical linkages between chromosomes and the mitotic spindle to allow the correct distribution of chromosomes from a mother cell to its two daughter cells during cell division. Kinetochores also control a cell cycle checkpoint known as the spindle assembly checkpoint (SAC), whose primary purpose is to halt cell cycle progression when the attachment of chromosomes to the spindle is delayed or derailed by external agents (e.g. small molecules that poison the mitotic spindle). The primary goal of Musacchio’s laboratory is to be able to reconstitute kinetochore and SAC function in vitro with purified components. In the last two years the group has made significant strides towards achieving this goal. Several papers, published in Molecular Cell, eLife, Current Biology, and Journal of Cell Biology, among others, describe this work. A former graduate student of Prof. Musacchio’s laboratory, Dr. Veronica Krenn, was awarded the prestigious Otto-Hahn Medal of the Max Planck Society in 2015. Prof. Musacchio was also awarded an Advanced Investigator grant of the European Research Council (ERC).
Mechanisms controlling the precise chromosomal segregation and the analysis of structure and function of the kinetochore are also at the core of Prof. Stefan Westermann’s research, who was appointed W3 Professor of Molecular Genetics at the UDE in spring 2015. He moved to Essen from the Institute for Molecular Pathology (IMP) in Vienna. His research interest centres on the question of how dynamic elements of the cytoskeleton, microtubules, cause tightly controlled movements of the chromosomes. The Westermann group is therefore studying the structure, function, and regulation of the kinetochore and analyses the binding mechanisms to the mitotic spindle e. g. by the so-called motor proteins. The group succeeded in reconstituting dynamic microtubules in vitro and making individual kinetochore complexes visible using total internal reflection fluorescence (TIRF) microscopy. This technique enabled the group to observe individual kinetochore complexes and microtubule-binding proteins with single-molecule sensitivity, and to reveal their mode of interaction.
The central role of the ubiquitin system in regulation of cell cycle control and other cellular processes is at the core of research in Prof. H. Meyer’s group (UDE, Molecular Biology I). The protein VCP/p97, a so-called AAA+ ATPase, has emerged as a key regulatory molecule in many ubiquitin-regulated reactions. Dysfunction of the system is relevant for various diseases like cancer, neurodegenerative and muscle diseases. Within the reporting period, one focus of the group was to elucidate mechanisms which ensure that cells pass on genetic information correctly to their progenitor cell during cell division. Errors within this process cause genetic instability, one attribute of cancer cells. The group was now able to show that in the case of genetic damage the molecular machine P97 contributes to degrading the dividing factor CDC25A and thereby prevents cell division and transfer of damaged DNA. In addition, the group studied the function of the spindle apparatus that ensures exact segregation of the chromosomes to the daughter cells. The group was able to demonstrate that an important factor, SDS22, contributes through regulation of protein modification to correcting errors in the attachment of chromosomes to the spindle to ensure equal distribution of chromosomes during cell division. The results were published in high-level scientific journals including EMBO Journal and Cell Cycle in 2014.
The cause of many diseases can be traced back to specific biochemical pathways, like for example protein homeostasis. It comprises control and repair mechanisms nature has evolved to ensure that all proteins are biologically active, localized to the proper cellular compartment, and present in an appropriate quantity. The failure of quality control can influence cell growth and cause severe diseases ranging from bacterial infections to neurodegenerative and arthritic diseases or cancer. The ZMB groups apply genetic, molecular biology and biochemical methods as well as methods from chemical biology to dissect key mechanisms of protein quality control.
Apart from the ubiquitin system which is at the centre of Prof. Meyer’s research, proteins characterized by a so-called PDZ domain as the protease hHtrA are also in the foreground of interest at the ZMB. Recent studies by a research team led by Prof. M. Ehrmann (UDE/ZMB Microbiology) provided evidence that this protease is able to degrade resistant debris of misfolded proteins occurring in Alzheimer’s and Parkinson’s disease. The researchers published the new finding in autumn 2015 in Nature Chemical Biology. The hHtrA protease recognizes if proteins have formed normal or unnatural structures, which tend to clump together. The protease specifically disintegrates the detrimental structures and degrades them, whereas the nonhazardous structures remain untouched. More studies are needed to clarify whether the new findings allow new strategies to be developed for the treatment of the corresponding neurodegenerative diseases.
Prof. Joachim Fandrey heads the Institute for Physiology at the UK Essen with a focus on the study of oxygen-dependent gene expression and the cellular oxygen sensor system. At the centre of interest is the transcription factor Hypoxia-Inducible Factor-1 (HIF-1) and its function and regulation under different physiological and pathophysiological conditions. An additional aspect concerns recently detected oxygen-binding proteins, which are the research focus of Junior Professor Dr. David Hoogewij, who joined the ZMB at the beginning of 2015.
In a recent study the group of Prof. Fandrey provided new evidence for the protective role of HIF-1α in dendritic cells during the pathogenesis of chronic inflammatory bowel disease.
Research at the Institute for Human Genetics, which is headed by Prof. Bernhard Horsthemke, addresses questions in the area of clinical and molecular genetics. The understanding of genetic and epigenetic factors in the development of human diseases is the central research interest. One focus is on the investigation of differences in gene expression caused by DNA sequence variations and DNA methylation, with a particular interest in genomic imprinting. The institute is currently engaged in nationwide networks to advance highly relevant topics in medicine. Prof. Horsthemke coordinates the BMBF “Network Imprinting Diseases”, which commenced its second funding period in 2015. Since 2012, the group has been contributing to the BMBF’s German Epigenome Programme (DEEP).
The interdisciplinary lineup of the ZMB as the embodiment of the UDE’s main research area of Biomedical Sciences is further consolidated by three members from the Center for Nanointegration (CENIDE). The group leaders Professors Stephan Barcikowski and Matthias Epple as well as Dr. Nils Hartmann work on the development of new materials for medicine and medical technology on the basis of nano-technology. To foster the network between the two research priority areas, scientists from CENIDE and the ZMB organized a “Nanobio Workshop” in March 2015 as a follow-up to the CENIDE Nanobiophotonics Symposium 2015.
One challenge which can only be addressed jointly arises from application of nanomaterials in biomedical practice. In biological media proteins tend to bind to nanoparticles, forming a “protein corona” and thereby affecting the biological identity and activity of nanomaterials optimized under idealized conditions. The analysis of the protein corona and the use of this information for optimization of the biomedical application of nanoparticles is a task that can only be solved if medical biologists and nanotechnology work together. Methods and results relating to this topic were summarized in a recent publication in Nature Protocols 2014 with a contribution by Prof. Shirley Knauer, ZMB.