Medizinerkolleg Münster - am 21. und 22. Januar 2021
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Medizinerkolleg Münster am 21. und 22. Januar 2021
Liebe Teilnehmer*innen,
wir begrüßen Sie herzlich zum Zwischenkolloquium des Medizinerkollegs 2020_1.
Da wir das Kolloquium leider nicht als Präsenzveranstaltung, sondern als Zoom-Konferenz abhalten
müssen, möchten wir Ihnen vorab ein paar Informationen zu diesem Format zukommen lassen:
Bei den Vorträgen ist eine Redezeit von 15min und Diskussionszeit von 5min vorgesehen.
Sie sind alle herzlich eingeladen, sich aktiv an den Diskussionen zu beteiligen und gerne viele Fragen
zu stellen. Wenn Sie gerade keinen Redebeitrag leisten möchten, bitten wir Sie das Mikrofon
auszustellen.
Im Rahmen eines wertschätzenden Miteinanders während Zoom-Konferenzen möchten wir Sie
bitten ihre Kamera einzuschalten, sofern dies für Sie technisch möglich ist.
Neben den Vorträgen wird es ein weiteres Präsentationsformat geben, welches die in den
vergangenen Jahren durchgeführten Postersessions ersetzt. Diese alternativen Postersessions
werden wie folgt ablaufen:
- Die Präsentierenden bekommen jeweils einen Breakoutraum zugeteilt und präsentieren Ihr
Thema in einer 5minütigen Kurzpräsentation. Anschließend kann 10min diskutiert werden.
Abstracts zu den Kurzpräsentationen finden Sie ab Seite 5 des Programmheftes
- Alle anderen Teilnehmer*innen können sich aussuchen, welchen Raum Sie besuchen und
werden gebeten sich möglichst gut auf die 5 angebotenen Räume zu verteilen.
- Nach 15min werden die Breakouträume geschlossen und für eine weitere Runde erneut
geöffnet. Sie haben die Möglichkeit 4 der 5 angebotenen Räume zu besuchen.
Wir wünschen allen Teilnehmer*innen ein spannendes und erfolgreiches Kolloquium,
Das Organisations-Team
Maurice Dellin (Kohortensprecher 2020_1)
Aliska Brugmans (Kohortenprecherin 2020_1)
Prof. Dr. Rupert Hallmann (Sprecher des MedK)
Dr. Jana Zimmermann (Studienkoordinatorin MedK)
1Programm 21.01.2020:
8:30 Begrüßung Prof. Dr. Rupert Hallmann
Vorträge
8:40 „Towards a novel small animal quantitative perfusion MRI reference Florian Gierse
standard“, Univ.-Prof. Dr. Schäfers, Klinik für Nuklearmedizin
9:00 „The impact of neutrophile priming on ROS production and Stina Becker
chemotaxis“, Univ.-Prof. Dr. Schwab, Institut für Physiologie II -
Vegetative Physiologie
9:20 „Functional and structural analysys of new KCNQ1 and KCNQ5 Maurice Dellin
disease associated mutations“, Univ.-Prof. Dr. Seebohm, Institut für
Genetik von Herzerkrankungen
9:40 „The role of junctional adhesion molecules in entosis“, Prof. Dr. Anne Kaschler
Ebnet, Institut für Medizinische Biochemie
10:00 Pause 15 min
Postersession I
10:15 PSI-BR01: „The Regulatory Role of Smarcb1 in the Proliferation of Aliska Brugmans
Neuronal Stem Cells“, PD Dr. Kerl, Klinik für Kinder- und
Jugendmedizin - Pädiatrische Hämatologie und Onkologie
PSI-BR02: „Studies on the influence of Fcy receptor stimulation on Annika Schwacha
the polarization of macrophages“, Univ.-Prof. Dr. Kiefer, European
Institute of Molecular Imaging (EIMI)
PSI-BR03: „In vitro studies on the function of cell surface heparan Stefan Krautschneider
sulfate in therapy resistance/radiation resistance of triple negative
breast carcinoma“, Prof. Dr. Greve, Klinik für Strahlentherapie -
Radioonkologie
PSI-BR04: „Sonic hedgehog activity regulation by its N-terminal Sophia Friederike Ehlers
peptide“, Prof. Dr. Grobe, Institut für Physiologische Chemie und
Pathobiochemie
PSI-BR05: „Impact of Standardized Endurance Exercise on Daniel Schiffmann
Experimental Autoimmune Encephalomyelitis in NOD Mice“, Univ.-
Prof. Dr. Klotz, Klinik für Neurologie mit Institut für Translationale
Neurologie
11:15 Pause 20 min
2Vorträge
11:35 „Characterization of radial spoke and central pair defects in patients Alina Biegemeier
with primary ciliary dyskinesia“, Univ.-Prof. Dr. Omran, Klinik für
Kinder- und Jugendmedizin - Allgemeine Pädiatrie
11:55 „Identification and characterisation of ciliary defects of the sperm Greta Zweigart
flagellum“, Univ.-Prof. Dr. Omran, Klinik für Kinder- und
Jugendmedizin - Allgemeine Pädiatrie
12:15 „The impact of Has3 mutations on congenital hydrocephalus“, PD Claus Seelmann-Eggebert
Dr. Schlingmann, Klinik für Kinder- und Jugendmedizin - Allgemeine
Pädiatrie
12:35 Mittagspause 45 min
Vorträge
13:20 „Influence of the metabolic state on neuronal signal processing“, Hannes Schmidt
Univ.-Prof. Dannlowski, Institut für Translationale Psychiatrie
13:40 „Effect of fluid shear stress on the membrane integrity of endothelial Ann Marleen Starke
cells“, Univ.-Prof. Dr. Gerke, Institut für Medizinische Biochemie
14:00 „Role of post-translational modifications of the Histone Demethylase Franca Carlotta Seifert
PHF8 in sensitization of Acute Myeloide Leukemia cells to ATRA“,
PD Dr. Mikesch, Medizinische Klinik A
14:20 Pause 15 min
Postersession II
14:35 PSII-BR01: „Alterations of spermatogonia in testicular tissues from Lena Charlotte Schülke
men with normal and impaired spermatogenesis“, PD Dr. Neuhaus,
Centrum für Reproduktionsmedizin und Andrologie
PSII-BR02: „Epigenetic pathways of resistance to BRD4-inhibitor Lisa Hüchtker
therapy in ETP-ALL“, Univ.-Prof. Dr. Rössig, Klinik für Kinder- und
Jugendmedizin - Pädiatrische Hämatologie und Onkologie
PSII-BR03: „Impact of Intermittent Fasting on Autoimmune Victoria Maria
Encephalomyelitis in NOD Mice“, Univ.-Prof. Dr. Klotz, Klinik für Lampkemeyer
Neurologie mit Institut für Translationale Neurologie
PSII-BR04: „Is the mutational status of TP53 relevant for the risk of Leon Gabriel Feldmeyer
relapse in pediatric Burkitt lymphoma?“, Univ.-Prof. Dr. Burkhardt,
Klinik für Kinder- und Jugendmedizin - Pädiatrische Hämatologie
und Onkologie
3PSII-BR05: „Determinants for the spread of Panton-Valentine Viktoria Rudolf
leukocidin positive Staphylococcus aureus in Africa“, Prof. Dr.
Schaumburg, Institut für Medizinische Mikrobiologie
15:35 Wrapup Tag 1 (10 min) Prof. Dr. Rupert Hallmann
Programm 22.01.2020:
Vorträge
8:30 „The role of PATJ in cell cycle and ciliogenisis“, Univ.-Prof. Dr. Dr. Thomas Mönnig
Krahn, Medizinische Klinik D
8:50 „Characterisation of the SARS-CoV-2 receptor ACE2 and the new Beate Claudine Gisela
subtype of type 2 pneumocytes in human lung tissue according to Conrad
clinical characteristica“, Univ.-Prof. Dr. Wiewrodt, Medizinische
Klinik A
9:10 „Molecular and cellular mechanisms controlling cell fate in Solveig Alexa Reinecke
primordial germ cells“, Univ.-Prof. Dr. Raz, Institut für Zellbiologie
9:30 "The role of NRG1-dependend circRNA in the functional regulation Helen Haupt
of the neuronal network in mouse brain", Univ.-Prof. Dr. Zhang,
Klinik für Psychische Gesundheit
9:50 Pause 15 min
Postersession III
10:05 PSIII-BR01: „Validation of remyelination promoting compounds Aurelia Valentina Seitz
identified in a drug screen“, Univ.-Prof. Dr. Kuhlmann, Institut für
Neuropathologie
PSIII-BR02: „Biofilm formation and phenotypic characterization of Carolin Laura Amelie Gawin
Staphylococcus aureus isolates from urine cultures“, Prof. Dr. Kahl,
Institut für Medizinische Mikrobiologie
PSIII-BR03: "Molecular Modulation of Host Cell Signaling Pathways Franziska Laing
by the Cell-Penetrating Effector Protein IpaH9.8 of Shigella Flexneri
in Tissue Culture Models", PD Dr. Rüter, Institut für Infektiologie
PSIII-BR04: "IGF/PI3K/AKT signaling pathway regulates β-Catenin Hanna Wattendorf
in Synovialsarcoma“,Univ. Prof. Dr. Hartmann, Gerhard-Domagk-
Institut – Sektion für Translationale Pathologie
4PSIII-BR05: Exploration of the Interaction between the Cell Niklas Beckmann
Adhesion Molecule JAM-A and RhoGDI1, a Regulator of the Rho
Family of GTPases“, Prof. Dr. Ebnet, Institut für Medizinische
Biochemie
11:05 Pause 15 min
Vorträge
11:20 „Optogenetic interference with epilepsy brain networks“, Univ.-Prof. Leo Hebbelmann
Dr. Faber, Klinik für Radiologie
11:40 „Studies on colibactin polyketide expression in E. coli“, Univ.-Prof. Ann-Kathrin Alraun
Dr. Dobrindt, Institut für Hygiene
12:00 „Ligand-induced Inhibition of the Slo3 Potassium-Channel“, Univ.- Johannes Lorenz
Prof. Dr. Strünker, Centrum für Reproduktionsmedizin und
Andrologie
12:20 „Characterization of TREK1 ion channel activators“, Univ.-Prof. Dr. Lucas Spohler
Dr. Dr. h. c. Meuth, Klinik für Neurologie mit Institut für
Translationale Neurologie
12:40 Rèsumè und Verabschiedung (15 min) Prof. Dr. Rupert Hallmann
5Poster-Abstracts:
Postersession I:
PSI-BR01: „The Regulatory Role of Smarcb1 in the Proliferation of Neuronal Stem Cells“
Aliska Brugmans
PD Dr. Kerl, Klinik für Kinder- und Jugendmedizin – Päd. Hämatologie und Onkologie
The tumour suppressor gene SMARCB1 encodes for a core subunit of the BAF (BRG1-associated
factor) chromatin remodelling complex. SMARCB1 is involved in the recruitment of the BAF complex
to target genes and therefore plays an essential role in the epigenetic modification of the DNA.
Mutations of SMARCB1 result in various pathologies: Biallelic loss-of-function mutations predispose
to the development of aggressive rhabdoid tumours, while smaller deletions or in-frame-mutations
are found in neurodevelopmental disorders, e.g. the Coffin-Siris syndrome (CSS).
Our group has established a genetically engineered mouse model with a 1148CDel Smarcb1
mutation, which develops a CSS-like phenotype including a hydrocephalus and cerebellar
abnormalities. We suppose that this mutation triggers the synthesis of longer Smarcb1 protein that
alters the composition and function of the BAF complex and consequently the expression of genes
and signalling pathways. We hypothesize that proliferation defects in radial glial cells lead to a
depletion of neural progenitor-derived cell populations.
This project aims to identify the molecular and biological mechanisms that lead to the observed
murine CSS-like phenotype. Using single-cell RNA-sequencing technology, we will investigate which
particular cell type(s) and signalling pathways are affected by the Smarcb1 1148C deletion. To
complement this analysis, we will perform a detailed histological examination of brain tissue from
mutant and control mice at adult and embryonic stages. Additionally, we will analyse the intracellular
localization of mutant Smarcb1 as well as BAF complex interaction partners.
PSI-BR02: „Studies on the influence of Fcy receptor stimulation on the polarization of
macrophages“
Annika Schwacha
Univ.-Prof. Dr. Kiefer, European Institute of Molecular Imaging (EIMI)
Atherosclerosis is a chronic inflammatory disease of the vessel wall characterized by lipid
accumulation and macrophage infiltration.
The differentiation and polarization of macrophages into pro-inflammatory ‘M1’ and anti-inflammatory
‘M2’ states represent the two extreme maturation programs of macrophages during tissue injury. The
consequences of macrophage polarization on the pathogenesis of atherosclerosis and how it can be
controlled to modulate and possibly ameliorate disease progression, are not fully understood.
A previous project of our group, studying the dynamics of macrophages during atheroma formation,
showed that the uptake of nanospheres coated with FcyR-specific ligands into macrophages led
6unexpected to a strong reduction in atherosclerotic plaque volume forming in the aortas of ApoE-/-
mice.
This project now aims to identify the molecular mechanisms underlying this atheroprotective effect.
It will be characterized if mIgG2a-beads, that bind with high affinity to Fcy receptors, on HoxB8-
derived macrophages in culture elict effects on polarization and activation of macrophages. Analysis
will include morphology, basal differentiation, signaling pathways and metabolic processes.
Stimulated cells will be compared to control cells.
Results will be verified in ApoE-/- mice.
In summary we expect to identify receptors and mechanisms, which upon stimulation with the FcgR-
Ligand mIgG2a modulate macrophage polarization and consequently immune function and therefore
might serve as potential targets for future pharmacologic manipulation of chronic inflammatory
diseases.
PSI-BR03: „In vitro studies on the function of cell surface heparan sulfate in therapy
resistance/radiation resistance of triple negative breast carcinoma“
Stefan Krautschneider
Prof. Dr. Greve, Klinik für Strahlentherapie - Radioonkologie
Radiation therapy is a key therapeutic component in the treatment of breast cancer. Although
treatment outcomes are improving, there are often recurrences due to development of resistances.
The molecular mechanisms behind that are not completely understood, but they may serve as
approaches to the development of new therapies.
Syndecans are the major source of cell surface heparan sulfate on all cell types, and of that family
Syndecan-1 is the most highly expressed proteoglycan.
In preliminary work, our group demonstrated that siRNA-mediated knockdown of Syndecan-1
increases the radioresistance significantly, possibly caused by the activation of integrins and focal
adhesion kinase (FAK). Moreover, stem cell characteristics were downregulated.
The enzymatic degradation of heparan sulfate led to similar activation of FAK as Syndecan-1
knockdown in the Caco2 cell line, suggesting that this functional domain may be involved in the
radiation resistance mechanism.
In this work, we will quantify cell survival after treatment with heparitinase and irradiation with 0Gy,
2Gy, 4Gy and 6Gy using colony formation assay on two triple negative breast cancer cells (MDA-
MB-231 and HCC1806). In addition, changes in invasiveness and motility will be determined using
Matrigel filter assay and time-lapse video microscopy, both without irradiation and with 2Gy.
Furthermore, we will determine changes in the expression of relevant stem cell markers (CD24,
CD44, CD133 and ALDH) after heparitinase treatment.
First experiments showed that the radioresistance of the cells was indeed increased after treatment
with heparitinase. We will conduct further experiments to verify this effect.
7PSI-BR04: „Sonic hedgehog activity regulation by its N-terminal peptide“
Sophia Friederike Ehlers
Prof. Dr. Grobe, Institut für Physiologische Chemie und Pathobiochemie
Hedgehog (Hh) morphogens are essential for embryonic tissue patterning as well as postnatal tissue
regeneration by forming spatial and temporal gradients while overactivation of Hh signaling is
implicated in human cancers. Hh is secreted to the cell surface dually lipidated, tethering it firmly to
the membranes outer leaflet. A proposed mode of Shh transportation involves solubilization by
proteolytic processing of the palmitoylated N-terminus and the cholesteroylated C-terminus. The
extended N-terminal peptide includes a Cardin-Weintraub (CW) motif with positively charged
residues, making it a target for certain proteases during shedding and facilitating its interaction with
negatively charged heparin sulfate glycosaminoglycan chains for transportation.
Morphogen receiving cells exhibit the receptor Patched 1 (PTCH1) which is inhibited by Hh ligand
and acts as a cholesterol pump removing cholesterol from the membrane to indirectly inactivate G-
protein coupled protein Smoothened (SMO). Hh biological activity is dependent on both the ability to
bind to PTCH1 as well as the extent of provoking inhibition. Introducing mutations to the extended
N-terminal peptide causes varying proteolytic processing, altered transportation and different
biological activity. Contrary to previous assumptions the N-palmitate is not crucial for PTCH1
inhibition which we show using eye development in Drosophila melanogaster as a model along with
in vitro differentiation assays. Beyond physiological cleavage shortened HH versions exhibit no
biological activity suggesting that certain amino acid residues are critical for PTCH1 interaction. The
project aims to further investigate the role of the extended N-terminal peptide regarding receptor
binding and the possible activation of a non-canonical pathway.
PSI-BR05: „Impact of Standardized Endurance Exercise on Experimental Autoimmune
Encephalomyelitis in NOD Mice“
Daniel Schiffmann
Univ.-Prof. Dr. Klotz, Klinik für Neurologie mit Institut für Translationale Neurologie
Multiple Sclerosis is a chronic neuroinflammatory disease of the brain and the spinal cord. Immune
cells infiltrate the brain by overcoming the blood-brain barrier and forward inflammation, axonal
degeneration, and demyelination [1]. Up to this day, there is insufficient treatment options for MS.
This study investigates the effect of forced endurance exercise in NOD mice with experimental
autoimmune encephalomyelitis (EAE), an animal model of MS. While it has already been shown that
endurance exercise has a positive impact in monophasic mouse EAE models, the NOD-EAE model,
which mimics a chronic secondary progressive MS disease course, has not been studied in this
regard [2,3].
Five days a week, the mice complete 75-minute-long interval exercise sessions in motorized running
wheels. They are weighed and clinically scored every day. Their immune cells in the CNS and
selected peripheral organs are analyzed using flow cytometry. CNS inflammation and cell infiltration
are histologically assessed.
8Though not statistically significant, preliminary analysis of the clinical score shows a trend towards
an attenuated disease course in the exercising mice. Furthermore, downregulation of
proinflammatory cytokines such as TNF-α, GM-CSF, and IFN-γ in the CNS could be observed.
Preliminary analysis also showed an upregulation of CTLA-4 and CD25 positive cells in inguinal and
mesenterial lymph nodes. The histological assessment has not yet commenced. Experiments with a
second group of mice will finish at the end of March.
References
[1] Dendrou CA, Fugger L, Friese MA (2015) Immunopathology of multiple sclerosis. Nat Rev
Immunol 15:545-558. doi:10.1038/nri3871.
[2] Rossi S, Furlan R, De Chiara V, Musella A, Lo Giudice T, Mataluni G, Cavasinni F, Cantarella
C, Bernardi G, Muzio L, Martorana A, Martino G, Centonze D (2009) Exercise attenuates the
clinical, synaptic and dendritic abnormalities of experimental autoimmune encephalomyelitis.
Neurobiol Dis 36:51-59. doi:10.1016/j.nbd.2009.06.013.
[3] Souza PS, Gonçalves ED, Pedroso GS, Farias HR, Junqueira SC, Marcon R, Tuon T, Cola M,
Silveira PCL, Santos AR, Calixto JB, Souza CT, de Pinho RA, Dutra RC (2017) Physical Exercise
Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Peripheral Immune
Response and Blood-Brain Barrier Disruption. Mol Neurobiol 54:4723-4737. doi:10.1007/s12035-
016-0014-0.
9Postersession II: PSII-BR01: „Alterations of spermatogonia in testicular tissues from men with normal and impaired spermatogenesis“ Lena Charlotte Schülke PD Dr. Neuhaus, Centrum für Reproduktionsmedizin und Andrologie Introduction: Over the last 30 years, about 30% of the patients treated at the Centre of Reproductive Medicine and Andrology (CeRA) were diagnosed with severely impaired sperm parameters, cryptozoospermia (crypto;
types. Thus, further research needs to be conducted before clinical implementation of JQ1 can be
templated.
My work in this context focusses on BRD4-inhibitor-resistant ETP-ALL cells, which have already
been established in our lab. The key question of my thesis is to find out which epigenetic pathways
these cells use to overcome BRD4 inhibition.
To this end, we already performed RNA-seq with ETP-ALL cells sensitive and resistant to BRD4-
inhibition and evaluated gene expression upon JQ1-treatment. I will further perform a CRISPR-Cas9
screen of epigenetic players relevant in BRD4-inhibitor-resistance to unravel potential targets to
overcome therapy resistance. Therefore, I have already transduced resistant ETP-ALL cells with
Cas9 and am currently evaluating the efficacy of the system.
References:
[1] Jain et al. (2016) Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL)
in adolescents and adults: a high-risk subtype, Blood.
[2] Donati, B., Lorenzini, E. & Ciarrocchi, A. BRD4 and Cancer: going beyond transcriptional
regulation. Mol Cancer.
PSII-BR03: „Impact of Intermittent Fasting on Autoimmune Encephalomyelitis in NOD Mice“
Victoria Maria Lampkemeyer
Univ.-Prof. Dr. Klotz, Klinik für Neurologie mit Institut für Translationale Neurologie
Multiple sclerosis (MS) is a chronical inflammatory disease of the central nervous system. The most
commonly used and best studied animal model for MS is the murine experimental encephalomyelitis
(EAE). It has already been shown that intermittent fasting (IF) ameliorates clinical course and
pathology in an acute, monophasic severe EAE-model of MS. In this study, we try to investigate
whether IF as a lifestyle factor shows an effect on the secondary progressive NOD-EAE model. This
animal model mimics the chronic secondary progressive multiple sclerosis disease course, which
hitherto lacks sufficient and effective therapeutic options. Our present findings show that IF might
have a slight tendency of improving the long term clinical course in female NOD-EAE mice. We did
not observe a difference in the clinical course of male mice. IF showed slight tendencies to reduce
IL17A, GM-CSF and IFNγ in the draining lymph nodes and might reduce the total amount of activated
T cells in the mesenteric lymph nodes. We will pursue to investigate a possible immunomodulatory
effect of IF in our NOD-EAE model and proceed by exploring effects on the demyelination in the
central nervous system. An ongoing second trial of mice with expected results in the end of March
increases our sample number and will help determine the effect of IF on the secondary progressive
NOD-EAE model.
11PSII-BR04: „Is the mutational status of TP53 relevant for the risk of relapse in pediatric
Burkitt lymphoma?“
Leon Gabriel Feldmeyer
Univ.-Prof. Dr. Burkhardt, Klinik für Kinder- und Jugendmedizin – Päd. Hämatologie und Onkologie
Burkitt lymphoma (BL) is the most common type of Non-Hodgkin Lymphoma (NHL) in childhood and
adolescence, accounting for 40-50% of all cases. With the current therapy according to the NHL-
BFM study group protocols the event free and overall survivals for pediatric Burkitt lymphoma
patients amounts to 80-90%. However, patients with refractory or relapsed disease have a dismal
prognosis, with survival rates of 20-30%. Treatment options for those patients remain limited. In our
latest study 25 out of 30 patients with refractory or relapse disease were found with a TP53 mutation.
We aim to understand more about functional aspects of this alteration as well as potential pathways
that are activated. As an in-vitro model an inducible shRNA-mediated knockdown of TP53 was
established in Burkitt-lymphoma cell lines. The knockdown was confirmed on transcriptional and
translational level. Through RNA sequencing of bulk RNA extracted of those cell lines we aim to
identify potential target genes for risk-based treatment and potential therapeutic targets to improve
outcome of the pediatric patients in the future.
PSII-BR05: „Determinants for the spread of Panton-Valentine leukocidin positive
Staphylococcus aureus in Africa“
Viktoria Rudolf
Prof. Dr. Schaumburg, Institut für Medizinische Mikrobiologie
The Panton-Valentin leukocidin (PVL) is a bicomponent pore-forming toxin which can be produced
by Staphylococcus aureus. The binding of PVL to granulocytes, monocytes and macrophages leads
to cell death and causes particularly necrotizing pneumonia and severe skin and soft tissue
infections. Previous studies have shown different prevalences of PVL-positive S. aureus in Africa
and Europe. While approximately 50% of S. aureus isolates are PVL-positive in Africa, the
prevalence of PVL-positive S. aureus in Europe is quite low (~ 2%). This raises the question why the
virulence factor is widespread in Africa compared to Europe.
Based on preliminary studies, we hypothesize that the reason is related to the host. Hence, a
German-African network was founded consisting of two German partner sites (Münster, Jena) and
three African partner sites (Gabon, Nigeria, Republic of the Congo). At each partner site we will draw
blood samples of 164 participants. The aim of our study is to compare the humoral immune response
and the cellular response between the African and Caucasian participants using methods such as
fluorescence-activated cell scanning (FACS), Western Blot and ELISA.
With this study we attempt to investigate the reasons for the spread of PVL-positive S. aureus in
Africa and we hope to foster the development of strategies to reduce PVL-associated diseases.
12Postersession III:
PSIII-BR01: „Validation of remyelination promoting compounds identified in a drug screen“
Aurelia Valentina Seitz
Univ.-Prof. Dr. Kuhlmann, Institut für Neuropathologie
Multiple Sclerosis (MS) is an autoimmune-mediated disease which damages oligodendrocytes, the
myelin forming and maintaining cells of the central nervous system. Demyelination and axonal
damage result clinically in neurological dysfunction. Remyelination, the formation of new myelin
sheaths by oligodendroglial lineage cells, can compensate for the loss of axon ensheathment, but
frequently fails in MS. Remyelination promoting compounds could complement existing treatments
to restore axonal integrity and neurologic function.
The consortium “BRAVEinMS” is dedicated to preventing MS disease progression by identifying
neuroprotective or remyelinating compounds. This project aims to establish dose-response curves
for eight compounds, previously identified in in silico and in vitro repurposing drug screens, using
induced pluripotent stem cell (iPSC) - derived oligodendrocytes. The iPSCs are obtained from
fibroblasts of healthy donors and patients with primary progressive MS. Following an established
protocol (Ehrlich, M. et al, 2017), iPSC - derived neural progenitor cells are differentiated into
oligodendrocytes using lentiviral transduction of the transcription factors SOX10, OLIG2 and NKX6.2.
After 21 days of differentiation, immature oligodendrocytes expressing the O4 cell-lineage marker
are sorted using fluorescence-activated-cell-sorting (FACS). The O4+ population is reseeded and
treated with the eight compounds at three different concentrations. After 32 days of differentiation
the number of oligodendrocytes expressing myelin basic protein (MBP), a marker of mature
oligodendrocytes, is quantified by immunocytochemistry staining (ICC) to determine the compounds
effects on oligodendroglial differentiation. The compounds impact on further crucial steps of
remyelination, namely oligodendroglial migration, proliferation and myelin sheath formation, is
investigated using live-cell-imaging, BrdU labelling and nanofiber assays.
PSIII-BR02: „Biofilm formation and phenotypic characterization of Staphylococcus aureus
isolates from urine cultures“
Carolin Laura Amelie Gawin
Prof. Dr. Kahl, Institut für Medizinische Mikrobiologie
Staphylococcus aureus is rarely found as the causing pathogen of urinary tract infections (UTI) [1].
In 2016, Schwartbeck et al. discovered unusual mucoid S. aureus isolates, recovered from the
airways of CF patients, who were chronically infected by S. aureus, which carried a 5 bp deletion in
the intergenic region of the ica operon, which is responsible for high-amount polysaccharide-
dependent biofilm formation [2]. We hypothesized that S. aureus isolates of UTI would be mucoid
and high biofilm formers.
The aim of our prospective study was to determine the prevalence of S. aureus cultured from urine
samples, to characterize these isolates in terms of mucoidy and biofilm formation.
13During our ongoing prospective study, we analyzed 57 S.aureus-positive urine cultures from 47
patients and randomly picked 10 colonies from every culture. The isolates were phenotypically
characterized in regard to size, hemolysis, mucoidy and pigmentation on Columbia blood (CB) and
Congo red (CR) agar. Biofilm assays were performed (n = 570).
The mucoid phenotype was visible for 37 isolates on CB and for 63 isolates on CR agar. Using the
static biofilm assay, 10 isolates were biofilm producers.
While we identified 63 isolates with mucoid phenotype on CR agar (11%), only 10 of these isolates
were high biofilm formers. Therefore, another unidentified mechanism for mucoidy is most likely
responsible for this mucoid phenotype. Next, we will repeat the biofilm assay with fibrinogen coated
wells to determine if the binding of the isolates, especially those of catheterized patients, to plastic
surfaces is impaired.
References:
[1] Walker J.N., Flores-Mireles A.L., Hultgren S.J. et al. (2017) Catheterization alters bladder
ecology to potentiate Staphylococcus aureus infection of the urinary tract, Proc Natl Acad Sci USA,
114(41):E8721-E8730
[2] Schwartbeck, B., Birtel,J., Treffon, J., Langhanki, L., Mellman, A., Kale, D., Kahl, J.,
Hirschhausen, N., Neumann, C., Lee, J. C., Götz, F., Rohde, H., Henke, H., Küster, P., Peters, G.
and Kahl, B. C. (2016) Dynamic in vivo mutations within the ica operon during persistence of
Staphylococcus aureus in the airways of cystic fibrosis patients, PLoS pathogens 12, e1006024
PSIII-BR03: "Molecular Modulation of Host Cell Signaling Pathways by the Cell-Penetrating
Effector Protein IpaH9.8 of Shigella flexneri in Tissue Culture Models"
Franziska Laing
PD Dr. Rüter, Institut für Infektiologie
Effector proteins are important virulence factors of pathogenic bacteria that target and subvert the
functions of essential host defense mechanisms. Typically, these proteins are injected into host cells
via a type III secretion system (T3SS). However, it was found that several effector proteins can also
enter host cells in a T3SS-independent manner.
One such bacterial-derived cell-penetrating effector is IpaH9.8 from Shigella flexneri, which can
autonomously enter the host cell and functions as a ubiquitin ligase, polyubiquitinating target host
cell factors of the immune signaling cascade and tagging them for degradation by the host cell
proteasome. Apart from their anti-inflammatory role in infections, these Cell-Penetrating effector
proteins could be engineered as "self-delivering" novel therapeutic molecules to modulate and
dampen harmful host immune responses.
First, the uptake of the recombinant IpaH9.8 into HaCaT and HT29 cells was investigated by flow
cytometry and confocal microscopy in a 2D setting. After verifying efficient translocation and
reviewing the functionality of IpaH9.8 the goal is to analyze its intracellular interactions in more
complex tissue culture models. The focus will be on the molecular modulation of the NFκB-host cell
signaling pathway, as this is already known and described as a central target (ubiquitination of the
"NF-kappa-B essential modulator" NEMO by IpaH9.8).
14PSIII-BR04: "IGF/PI3K/AKT signaling pathway regulates β-Catenin in Synovialsarcoma“
Hanna Wattendorf
Univ. Prof. Dr. Hartmann, Gerhard-Domagk-Institut – Sektion für Translationale Pathologie
Synovial sarcoma is an aggressive soft tissue tumor which particularly occurs in young adults. Given
high rates of local recurrences and metastases, clinical outcome in patients with advanced disease
is poor. For the development of novel therapeutic strategies, a precise understanding of the
molecular mechanisms involved in synovial sarcoma tumorigenesis and progression is essential.
The molecular hallmark of synovial sarcoma is a specific chromosomal translocation
t(X;18)(p11;q11) resulting in the fusion protein SS18-SSX, which acts as a transcriptional
dysregulator. SS18-SSX-dependent upregulation of IGF-II in synovial sarcoma cells has been
described before, protecting the tumor cells against apoptosis and leading to proliferation through
oncogenic activation of the IGF-IR and its downstream targets. Furthermore, an aberrant activation
of the WNT/β-Catenin signaling pathway, including nuclear β-Catenin accumulation, associated with
elevated TCF transcription factor activity and high expression levels of β-Catenin targets, was
reported to be of particular importance for synovial sarcoma cell proliferation. As the mechanism of
β-Catenin activation in synovial sarcoma is still elusive, this work aims to examine if aberrant IGF-
IR/PI3K/AKT-signaling exerts regulatory effects on the WNT/β-Catenin pathway. Inhibition of the
IGF-IR/PI3K cascade by RNAi or pharmacological approaches showed decreasing β-Catenin protein
levels and reduced nuclear β-Catenin activity in human synovial sarcoma cell lines. Conversely,
stimulation of synovial sarcoma cells with recombinant IGF-II resulted in elevated expression of
active β-Catenin and its downstream targets. These data imply that the IGF-IR/PI3K pathway is
crucially involved in β-Catenin activation in synovial sarcoma and therefore represents an attractive
target for pharmacological intervention.
PSIII-BR05: „Exploration of the Interaction between the Cell Adhesion Molecule JAM-A and
RhoGDI1, a Regulator of the Rho Family of GTPases“
Niklas Beckmann
Prof. Dr. Ebnet, Institut für Medizinische Biochemie
RhoGTPases are of major importance in a wide range of cellular responses, including changes to
the cytoskeleton and cell adhesion. That is why their activity has to be strictly controlled in order to
determine which pathway has to be activated, depending on the context and stimulus.
RhoGTPases are commonly located on membranes attached to a kinase. They cycle between an
active GTP-bound and an inactive GDP-bound form. This process is, amongst others, regulated by
guanine nucleotide dissociation inhibitors (RhoGDIs).
RhoGDIs can bind RhoGTPases and thereby extract them from membranes in order to inactivate
as well as stabilize them in the cytoplasma. By this mechanism RhoGDIs indirectly control
processes like cytoskeletal organisation and cell adhesion.
Previous experiments like mass spectroscopical analyses, performed by our research group,
suggest that RhoGDIs also interact with JAM-A.
15JAM-A is expressed on the surface of endothelial and epithelial cells as a component of tight
junctions which maintain the integrity of barriers formed between polarized cells.
Our project aims to further investigate a probable interaction between RhoGDI and JAM-A to better
understand the process and different types of regulation of cell-cell-adhesion.
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