Program
Abstracts
1 Cellular and viral determinants of the life cycle of positive strand RNA viruses of the family Flaviviridae & Cellular and viral determinants for Norovirus Entry
Institute of Virology and Cellbiology
(12 + 8 persons, de/eng, B.Sc./M.Sc.)
Part I: Cellular and viral determinants of the life cycle of positive strand RNA viruses of the family Flaviviridae (Dr. Isken)
The focus of this workshop will be an introduction of our work with positive strand RNA viruses of the family Flaviviridae. The main focus of research is the elucidation of determinants of viral RNA replication, virion morphogenesis and virus-host interactions. This workshop will consist of a seminar that outlines current research on Hepatitis C Virus (HCV) and related viruses such as bovine viral diarrhea virus (BVDV). The second part will focus on the practical techniques used in our group. Here, we will demonstrate the different applications of reverse genetic approaches to dissect determinants important for different aspect of the viral life cycle. Demonstrations will include methods such as cell culture techniques to determine viral biotypes and virus titers of BVDV or Vaccinia Virus, immunofluorescence assays to control for viral protein expression during replication (HCV and BVDV) and luciferase reporter assays for the quantitative measurements of viral RNA replication.
Part II: Cellular and viral determinants for Norovirus Entry (Prof. Dr. Taube)
The focus of this workshop will be an introduction of our work with positive strand RNA viruses of the family Caliciviridae.The main focus of research is the elucidation of determinants for virus attachment and entry. This workshop will consist of a seminar that outlines current research on Human Norovirus (HuNoV), Murine Norovirus (MNV) and related Caliciviruses, receptor specificity and host restriction factors. The second part will focus on the practical techniques used in our group. Here, we will demonstrate the different applications of protein expression and purification of virus like particles (VLPc). Reverse genetic approaches will be used to dissect determinants important for different aspect of the viral life cycle. Demonstrations will include methods such as cell culture techniques to determine amplify Murine and Human Norovirus in tissue culture, generation of complete and subviral particles using the baculovirus expression system.
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2 Looking for the needle in a haystack - how to develop novel drugs using NMR experiments
Institute of Chemistry (Prof. Dr. Peters)
(15 persons, de/eng, end B.Sc./M.Sc.)
NMR spectroscopy provides powerful tools at different stages in the process of drug design. In particular, so called fragment based approaches benefit significantly from NMR techniques that have been developed over the past fifteen years.
The workshop will give an introduction into the basic experiments used in NMR based drug design. In general, ligand based and proteinbased approaches can be applied. The pros and cons of either approach will be illustrated using case studies ranging from enzymes as drug targets to membrane proteins to native viruses to whole cells. The emphasis of this workshop is on practical aspects of this novel methodology and no prior knowledge in the theory of NMR spectroscopy is expected.
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3 Structure-based design of an antiviral compound
Institute of Biochemistry (Prof. Dr. Hilgenfeld)
(8 persons, de/eng, B.Sc.)
This workshop will consist of an introduction to structure-based drug design (SBDD) and a tour of the Institute of Biochemistry where various techniques required for SBDD (recombinant target protein production, crystallization, and diffraction data collection) will be briefly explained. This will be followed by hands-on inhibitor docking experiments in the computer pool.
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4 Kristallographie und Röntgenbeugung
Institut für Biochemie (Dr. Mesters)
(8 Personen, de/eng, B.Sc.)
Kurz nach der Entdeckung des Röntgenlichts durch Wilhelm Röntgen in 1895 (Nobelpreis 1901) zeigte Max von Laue in 1912 (Nobelpreis 1914) die Beugung von Röntgenlicht an Kristallen. Dies ebnete letztendlich den Weg für die Bestimmung der ersten Proteinstruktur, Myoglobin, durch John Kendrew in 1958 (Nobelpreis 1962). Die PDB (Protein Data Bank; www.rcsb.org/pdb/) umfasst gegenwärtig mehr als 90.000 Strukturen wie zum Beispiel die Struktur des Ribosoms oder die der GPCRs (G-Protein gekoppelte Rezeptoren; Membranproteine). Der Großteil dieser Strukturen (±90%) verdanken wir der Kristallographie und Röntgenbeugung. Kenntnis der dreidimensionalen Struktur ist zwingend erforderlich für die Aufklärung der Beziehungen zwischen Struktur und Funktion. Außerdem sind die Strukturen für die gezielte Optimierung wichtiger Enzymen und erfolgversprechenden Leitverbindungen in der Forschung (Protein Engineering und Drug Design) unerlässlich.
Im Workshop wird nebst einer kurzen Einführung in die Kristallographie und Röntgenbeugung ein kleines Protein kristallisiert. Wie damals Max von Laue, wird im Labor die Beugung von Röntgenlicht an diese Proteinkristalle gezeigt und besprochen. Ziel des Workshops ist es u.a. Barrieren abzubauen und die Methodik zugänglicher für junge Forscher(innen) zu machen.
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5 Quantitative analysis of protein nucleic acid interactions using the example of HIV-1 reverse transcriptase
Institute of Molecular Medicine (Prof. Dr. Restle)
(5 persons, de/eng, end B.Sc.)
Decoding the role of protein nucleic acid interactions in the regulation of transcription, translation, DNA replication, repair and recombination as well as RNA processing, translocation and RNAi has revolutionized our understanding of many cell biological processes and mechanisms in pathogenesis. This workshop gives an insight to some key technologies for quantitative and structural analysis of protein nucleic acid interactions using the example of retroviral replication. Practical examples of techniques based on fluorescence (e.g. equilibrium and pre-equilibrium measurement) and single-molecule FRET will be elucidated. Depending on the number of participants working out a concrete experiment is possible.
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6 SE: Gezielte Modifikation der Blut-Hirn-Schranke mittels rekombinanter Adeno-assoziierter Viren
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie (Dr. Helge Müller-Fielitz) (15 Personen, de, B.Sc.)
Die Erforschung von neurodegenerativen Erkrankungen (z. B. Alzheimer und Multipler Sklerose) ist ein wichtiger Teil der aktuellen Neurowissenschaften. Allerdings ist die Untersuchung und Entwicklung möglicher Therapieansätze schwierig, da das Gehirn ein immunprivilegiertes Organ und im Vergleich zu anderen Organen nur schwer zugänglich ist. Ein Hauptfaktor dafür ist die Blut-Hirn-Schranke. Sie stellt eine Barriere dar, über die die Migration von Zellen (z. B. Immunzellen) und Pathogenen sowie der Stofftransport von Metaboliten und Signalmolekülen reguliert werden. Durch ihre Funktionen bildet die Blut-Hirn-Schranke ein attraktives Ziel für Grundlagen- aber auch Therapie-orientierte Forschung. Aufgrund des komplexen Aufbaus und der Interaktion von mehreren Zelltypen sind in vitro Experimente nur bedingt möglich.
Das Seminar soll die Möglichkeiten der gezielten Modifikation der Blut-Hirn-Schranke und insbesondere des Gehirnendothels in vivo behandeln. Dabei liegt der Fokus auf der Verwendung rekombinanter Adeno-assoziierter Viren, die mittels Cre-loxP Systems oder Kapsid-spezifischem Targeting für Knockout/in-Studien verwendet werden können.
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7 SE: Magnetic Particle Imaging
Institute of Medical Engineering (Prof. Dr. Buzug)
(12 persons, de/eng, B.Sc.)
MPI is a new tomographic imaging modality capable of imaging the distribution of superparamagnetic nanoparticles (SPIOs) and was recently invented at Philips research, Hamburg (2005). The institute of medical engineering started to investigate in MPI in 2007 and was the first to demonstrate the feasibility of the new single-sided MPI scanner geometry. Our further research activities are magnetic particle spectroscopy (MPS), efficient reconstruction, simulation studies and design of optimal nanoparticles for MPI. The principle of MPI is based on the nonlinearity of the particles' magnetization curve. When exposed to an oscillating magnetic field (drive field), the spectrum of the responding magnetization contains not only the base frequency f but also higher harmonics that are exploited for imaging. Spatial encoding is achieved by superposition of a static non-uniform selection field providing a single field-free point (FFP) and high field strength in its vicinity. The FFP is steered through the object of interest by means of the aforementioned drive field. In this way, data for reconstructing the particle distribution can be acquired with a recording coil. Here, it is exploited that only particles in the direct neighborhood of the FFP contribute to the signal, whereas afar particles stay in saturation.
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8 The molecular ruler poly proline with single molecule FRET
Institute of Physics (Prof. Dr. Hübner)
(4 persons, de/eng, end B.Sc./ M.Sc.)
In the workshop, the students will get a brief introduction into fluorescence resonance transfer with single molecules. There will be a hands-on in the lab were the students make smFRET experiment where the energy transfer in the classical molecular ruler poly proline will be measured. In the Institute of Physics smFRET is applied to study viral or bacterial proteins. The main focus lies on the investigation of protein folding and the formation of a protein-protein-complexes, for example the RNA-polymerase, assembled from non-structuralprotein 7 (nsp7) and non-structural protein 8 (nsp8), from the Feline Coronavirus or the complex formation of ESAT-6/CFP-10 complex from Mycobacterium tuberculosis. With the advent of single-molecule methods the process of complex formation is becoming accessible to direct observation.
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9 SE: Current therapy strategies in HIV infections
Institute of Medical Microbiology and Hygiene (Prof. Dr. Rupp)
(15 persons, de/eng, B.Sc.)
The incidence of newly detected HIV- patients in Germany did ot change inthe last decade. Almost 3000 people get diagnosed with acute or chronicHIV- infection per year, sometimes already progressed to AIDS. However, theperspective for those patients increased tremendously in recent years, dueto the availability of highly active antiretroviral therapy. In thisseminar we will discuss current treatment options in patients with HIVinfection. Patient cases will be presented to make the attendants familiarwith daily routine in HIV clinics. A special focus will be given thedifferent molecular ways to attack HIV in a human cell. Additional targetsin the HIV-host interaction will be highlighted to reconsider currenttreatments and speculate about novel drugs that might improve treatmentefficacy. Drug-drug interactions and side-effects of the most commonsubstances in treating HIV will be addressed in the context of the life-long necessity to treat the infection. Students with interest in virology,antiviral treatments and infectious diseases are highly welcome to join theseminar.
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10 Key position of stem‐like cells in malignant human glioma
Clinic for Neurology (PD Dr. Zechel)
(15 persons, de/eng, B.Sc.)
Malignant glioma, such as glioblastoma multiforme (GBM) and gliosarcoma (GSarc), harbor a subpopulation of cells, referred to as BTSC (brain tumor stem cells). BTSCs exhibit similarities to neural stem cells (NSC) and neural progenitors (NPC), self‐ renew and produce orthotopic tumors in mouse models.Recent data proposed that BTSCs constitute a lineage of self‐ renewing cell types expressing a range of markers of forebrain lineages. Moreover, experimental data provided evidence that BTSCs survive standard radio‐ and chemotherapy and become responsible for tumor regrowth. In 2012, a genetically engineered mouse model proved this and showed that a restricted cell population of slowly dividing GBM cells propagated tumor growth after standard chemotherapy. Notably, BTSCs also contribute to the rich network of vessels and capillaries developing during gliomagenesis by secretion of growth factors, vascular mimicry and transdifferentiation. Together these findings suggest that elimination of BTSCs by specific targeting or differentiation will be the crucial step on the way to improved glioma therapy.
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11 Heart and Heredity - Functional Genomics of Atherosclerosis and Myocardial Infarction
Institute of Integrative und Experimental Genomic
(Jaafar Al-Hasani, M.Sc.) (12 persons, de/eng, B.Sc.)
Myocardial infarction (MI), commonly known as a heart attack, is a major cause of morbidity and mortality worldwide, thus also called killer number one. MI is not only influenced by many environmental factors or physical conditions, such as smoking, alcohol, stress, diabetes or high blood pressure, but the risk can also be inherited. The aim of our group, led by Prof. Erdmann, is to identify and to understand the genetic basis of cardiovascular diseases (CVD), such as Atherosclerosis, a major predisposition for MI, and MI. Very recently, and together with Prof. Schunkert, Prof. Erdmann contributed successfully in identifying risk genes for MI using genome wide association studies (GWAS). Until now, 46 risk genes have been identified. In the coming years, we aim to go beyond GWAS and elucidate the functional role of each of the already identified risk genes using in vitro and in vivo models. Especially, we combine different approaches, integrating systems biological aspects with genomic, transcriptomic and metabolomic data, to understand the underlying pathomechanism of each risk gene.
The workshop will include two parts: a theoretical and a practical part. The theoretical part will include an overview about Heart and Heredity as well as a short introduction into GWAS. The second, practical part will take the participants to learn about several methods of molecular and cell biology which are used in our lab, like cell culture techniques for differentiation of murine Embryonic Stem Cells (mESC) to cardiomyocytes or calcifying cells, and the transfection of mammalian cells using plasmids with reporter genes, to name a few. Also, the participants will learn about histological analysis of mouse heart sections and go throughout the different anatomical structures of the heart under microscopy.
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12 Viruses - blessing or a curse
Institute for History of Medicine and Science Research
(Dominik Mahr) (12 Personen, de, B.Sc./ M.Sc.)
In this workshop you will get the possibility to discuss a ethical topic from the area of conflict of virology and gene technology. The introduction may be a provoking question or a short text to make sure everybody is arguing on the same basis.
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13 Immunologic Research at the Institute for Systemic Inflammation Research
Institut für Systemische Entzündungsforschung (Prof. Dr. Manz)
(12 persons, de/eng, B.Sc./ M.Sc.)
The ISEF conducts leading basic and translational immunological research focusing on the crosstalk between the innate and the adaptive immune system (www.isef.uni-luebeck.de). ISEF researchers contribute to multiple research and teaching consortia at the University of Lübeck (UzL), such as the Excellence Cluster "Inflammation at Interfaces", the SFB/TR 22 “Allergic Immune Responses of the Lung”, the SFB 654 “Plasticity and Sleep” and the Research Training Group (GRK) 1727 "Modulation of Autoimmunity". Further, the ISEF initiated and organizes the recently funded International Research Training Group (IRTG) 1911 "Immunoregulation of Inflammation in Allergy and Infection" in close collaboration with the University of Cincinnati and Cincinnati Children’s Hospital, a leading research organization in the US.
This seminar will provide an overview of the ISEF activities, with a particular focus on research and training opportunities in the context of the IRTG1911 (www.irtg1911.uni-luebeck.de). In this consortium, state of the art immunological methods based on genetically modified mouse models, multicolor flow cytometry, cell sorting and confocal microscopy are applied to study the immune mechanisms controlling the development of allergic asthma and food allergy and diseases triggered by infection with intracellular pathogens including Toxoplasma gondii, Leishmania major, Mycobacterium tuberculosis and Lymphocytic choriomeningitis virus. The main goal of the IRTG projects is to broaden our understanding of pathogen sensing, activation and modulation of innate immune cells, their crosstalk with pathogen-specific adaptive immunity and the resolution of such immune response. The students working within the IRTG1911 projects closely collaborate with other ISEF students and UzL scientists involved in studies on autoimmune diseases and are integrated in local research and training networks.
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14 From Bench to Bedside – Ein Überblick über die translationale chirurgische Forschung in Lübeck
Sektion für Translationale Chirurgische Onkologie
& Biomaterialbanken (Prof. Dr. Dr. Habermann)
(5 -10 Ppersonen, de/eng, B.Sc./ M.Sc.)
Die Sektion für Translationale Chirurgische Onkologie & Biomaterialbanken der Universität zu Lübeck unter der Leitung von Prof. Dr. Dr. Habermann führt schwerpunktmäßig Untersuchungen auf dem Gebiet der kliniknahen onkologischen Forschung durch. Hierbei werden alle üblichen Labortechniken sowie die meisten molekularbiologischen Untersuchungsmethoden in fünf spezialisierten Laboreinheiten angewandt: Klinische Probenaufbereitung, Histologie, Zellkultur, Biomics (Genome-, Transkriptom- und Proteinanalysen), Mikroskopie mit DNS-Cytometrie.
Auf dem Gebiet der Tumorforschung gilt das besondere Interesse dem kolorektalen Karzinom, dem häufigsten Tumor des Verdauungstraktes. Untersuchungen zu Veränderungen auf DNA-, RNA- und Protein-Ebene sollen dabei helfen, grundlegende Mechanismen der Karzinomentstehung zu entschlüsseln und hierbei innovative Biomarker zu identifizieren, die für eine verbesserte Früherkennung, Individualdiagnostik, Therapie, Prognose und Nachsorge eingesetzt werden können. Die grundlegenden Untersuchungen hierfür werden insbesondere mittels Chip- bzw. Array-Technologien (arrayCGH, microarrays, protein-chips, SELDI, tissue-arrays) als auch mit Hilfe der 2-DE Technik durchgeführt. Identifizierte Biomarker insbesondere des Zellzyklus, der Tumorzellproliferation, der Metastasierung und der Apoptoseregulierung stehen im Vordergrund weiterführender Analysen, mittels derer die Wertigkeit einzelner Marker für innovative Therapien getestet wird.
Ein weiterer Schwerpunkt der Tumorforschung gilt dem Aufbau der überregionalen Tumorbank „Kolorektales Karzinom“, der dazu führen soll, eine qualitativ hochwertige Gewebe-, Blut- und klinische Datensammlung aufzubauen. Für die Betreibung der überregionalen Tumorbank wurden gemeinsame Standard Operation Procedures (SOP’s) entworfen, die sich an den aktuellen datenschutzrechtlichen und ethischen Vorgaben ausrichten. In der Kryobank werden sowohl Gewebe als auch Blutproben mit ihren klinischen Parametern gemäß der jeweiligen SOP’s erfasst.
Das Seminar wird einen Überblick über den aktuellen Alltag in der Sektion Translationale Chirurgische Onkologie & Biomaterialbanken bieten. Es wird exemplarisch ein kompletter Workflow in der klinischen Forschung von der Probensammlung im Operationssaal, über die molekulare Untersuchung bis hin zum klinischen Test dargestellt. Neben illustrativen Vorträgen wird eine Laborführung den Ablauf in der chirurgischen Forschung untermalen.
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15 Human neurons derived from induced pluripotent stem cells
Institute of Neurogenetics (Dr. Capetian and Dr. Seibler)
(8 persons, de/eng, end B.Sc./M.Sc.)
A new type of pluripotent cells known as induced pluripotent stem (iPS) cells has recently gained increasing importance to study disease mechanisms in a biologically relevant cell system. These cells share the pluripotent characteristics of embryonic stem cells but are instead generated via direct reprogramming of the patients’ own somatic cells.
The workshop will give an introduction to the generation of iPS cells and their subsequent differentiation into disease-relevant neuronal subtypes. Further, participants will get the opportunity to have a look on cells in the differentiation process and to perform a short live-cell imaging experiment in our lab.
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