Aktuelle Masterarbeitsthemen der Forschungsgruppe Pharmazeutische Biologie
Current Master's Theses-Projects of the Research Group in Pharmaceutical Biology
| Forschungsgebiet Research Field | Kontakt Betreuer/in Contact Supervisor | MSc Pharmazie | MSc Drug Sciences | Bemerkungen Comments |
|---|---|---|---|---|
Natural product discovery pipeline to identify antidotes against amatoxin toxicity: Targeting OATP1B3-mediated uptake The poisonous mushroom Amanita phalloides, commonly known as the death cap mushroom, contains amatoxins (e.g. a-amanitin), potent hepatotoxins leading to severe liver damage and potential fatal liver failure. The natural product silibinin, from milk thistle (Silybummarianum), is one of the antidotes (Legalon SIL®) available to treat amatoxin intoxications. Nevertheless, the mechanism of action and efficacy of silibinin has yet to be fully determined. Limited studies suggest that one hepatic uptake transporter, the organic anion-transporting polypeptide 1B3 (OATP1B3), may play a crucial role. Further investigations are therefore needed to first confirm these data and clarify the mechanism of this antidote. Finally, it would be highly relevant to delve deeper into the inhibition of OATP1B3 as a treatment of Amanita phalloides by identifying other natural inhibitors. The master's thesis project is a collaboration between the Pharmaceutical Biology and Biopharmacy research groups. Within the project we intend to screen our in-house library of crude extracts from plants and fungi readily available. A previously established cell-based assay using MDCKII cells stably expressing OATP1B3 transporter will be utilized to screen the extracts library. Selected extract hits will be further applied to an HPLC-based activity profiling approach to localize active compounds in these extracts. In brief, extracts will be fractionated by analytical HPLC, micro-fractions will be collected, and tested in the in vitro assay to generate the so-called activity profile. Scale-up extraction of selected plant extracts will enable to isolate the active natural products and to determine the affinity profile of these compounds on OATP1B3. Finding new OATP1B3 inhibitors is an important endeavor as it may pave the road for new therapeutic treatments for Amanita phalloides poisoning. Methods: assay screening, cell culture, molecular biology methods to confirm protein expression, HPLC-MS, micro-fractionation, various chromatographic techniques to isolate pure compounds from crude extracts. | Dr. Eliane Garo and Dr. Anima Schäfer | nein | ja | This is a multidisciplinary project and the student will be supervised by both Anima Schäfer (Biopharmacy) and Eliane Garo (Pharmaceutical Biology). This project is therefore advertised in both groups. |
Target identification for novel natural product inhibitors of oncogenic MAPK/ERK and PI3K/AKT pathways in melanoma The incidence of malignant melanoma has dramatically increased over the last years. It has been shown that melanoma has the highest mutation frequency of all common cancers. These mutations are often found in the MAPK/ERK and PI3K/AKT signaling pathways, which are key drivers for the development of the disease. Specific inhibitors such as vemurafenib (Zelboraf®) and cobimetinib (Cotellic®) show spectacular initial results in the clinic, but most patients relapse within just a few months due to drug resistances. Combination therapy can improve overall survival rates, however, the currently available options are still limited. Novel inhibitors targeting oncogenic ERK and AKT signaling in melanoma are therefore urgently needed. To tackle this issue, a generic approach was used: An innovative high-content screening assay was developed that quantifies downstream inhibitory activity at ERK and AKT level. To this end, we screened our in-house library of 2,576 crude plant extracts as well as additional 25,696 pure natural and synthetic compounds in collaboration with a high-throughput facility (EU-OPENSCREEN). A total of 46 active compounds were confirmed as downstream inhibitors of ERK and/or AKT with IC50 values in the low micromolar range. Current efforts are aiming towards target identification of the most promising hits, which can then be developed into lead compounds for future drug development. With this master’s thesis project, you will have access to state-of-the-art drug discovery methods. You will learn proper aseptic techniques to maintain a sterile environment in prokaryotic (E. coli) and mammalian (HEK293) cell culture. Your work will include gene cloning and you will utilize a previously established protein production setting to express and purify protein mutants that are clinically relevant in malignant melanoma. Finally, you will assess the biophysical and biochemical properties of our newly discovered inhibitors on your produced protein mutants. Methods: Eukaryotic and prokaryotic cell culture, molecular biology methods including cloning techniques, protein production, testing of pure compounds in biophysical/-chemical experiments | Dr. Eliane Garo | nein | ja | This work will be conducted in the laboratories of the Pharmaceutical Biology research group at the University of Basel under the direct supervision of PhD student Maria Karpouchtsi. |
Biosynthesis of bacterial natural products Information: The work will comprise the investigation of enzymatic tailoring steps for the formation of bioactive tropone or polyketide natural products from terrestrial and marine bacteria, which often serve as antibiotics or toxins. The work will include gene cloning and heterologous production of proteins in Escherichia coli as well as the biochemical investigation of enzyme functionalities, e.g., by photometric and/or HPLC-based assays. Enzymatic products and intermediates will be identified by LCMS and NMR spectroscopy. The goal is to elucidate the underlying enzymology and gain a better understanding of how these compounds are formed in bacteria. This work will be conducted in the laboratory of the Pharmaceutical Biology at the Pharmacenter, University of Basel. Methods: Molecular biology & protein purification, enzyme assays, HPLC-MS, various chromatographic techniques, NMR for structural characterization of enzyme products | Prof. Robin Teufel | ja | ja | |
Zwischen Futter und Arznei - das Potential wirkstoffreicher Grünlandpflanzen der Alpenregion zur Steigerung der Resilienz von Wiederkäuern Auf Naturwiesen, aber auch in Saatgutmischungen für Grünland finden sich zahlreiche sekundärstoffreiche Pflanzen. Von Wildwiederkäuern, aber auch von Rindern, Schafen und Ziegen ist bekannt, dass diese Pflanzen gezielt gefressen werden. Auch werden zahlreiche Pflanzen der natürlichen Wiesenflora des Alpenraums traditionell seit Generationen von Landwirtinnen und Landwirten zur Gesunderhaltung oder zur Therapie ihrer Nutztiere verfüttert. Über viele Pflanzen liegen auch Erkenntnisse aus der Tierernährungsforschung vor. In einer mehrstufigen Literaturarbeit soll mit der Methodik des «systematic review» das Potential ausgewählter Pflanzen zur Steigerung der Resilienz der Hauswiederkäuer erarbeitet werden. In einem ersten Schritt werden durch einen Abgleich von früheren Arbeiten zur Tierernährung und Ethnoveterinärmedizin mit Verbreitungsgebiet und Häufigkeit sekundärstoffreicher Grünlandpflanzen in der Alpenregion sowie als Bestandteil in Saatmischungen für Dauergrünland in der Schweiz besonders interessante Pflanzenarten zusammengestellt und eine Auswahl für eine gewisse Anzahl Pflanzenarten getroffen. Diese können auch aus einer Pflanzenfamilie stammen (zum Beispiel aus der Familie der Brassicaceae). Anschliessend wird eine systematische Literatursuche in den üblichen online-Portalen durchgeführt. Anhand von Ein- und Ausschlusskriterien werden gezielt die Publikationen herausgefiltert, in denen für die Resilienz von Wiederkäuern relevante Untersuchungen beschrieben sind. Dies können phytochemische, in vitro, ex vivo und in vivo Studien sein. Die Ergebnisse dieser Untersuchungen werden zunächst systematisch tabellarisch erfasst und anschliessen in der Übersicht ausgewertet und diskutiert. Keywords | Florian Leiber und Michael Walkenhorst | ja |
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How to improve treatment of preterm contractions: effects of tocolytic medications on specific key players in transformed myometrial cells Pregnancy is a critical period for medical care, well-being of both the woman and the foetus are to be considered. In particular, the choice of – synthetic and herbal – medications to treat various disorders requires a careful risk/benefit evaluation. This is also the case for the treatment of preterm birth, defined as birth before 37 weeks of pregnancy, which is the number one cause of neonatal deaths, and the second leading cause of childhood death under 5 years of age. Standard treatment includes pharmacological inhibition of myometrial contractions. Several types of tocolytics are currently in use, including atosiban, a competitive oxytocin-vasopressin antagonist, nifedipine, a calcium channel-blocking agent, in some cases hexoprenaline, an agonist of beta-adrenergic receptors and, in Switzerland, the herbal medicine Bryophyllum pinnatum often as add-on therapy. However, not all patients respond equally to the same tocolytic treatment and often time is lost in optimising strategies. Screening procedures to predict which patients are responders to each of the available tocolytics would be extremely helpful. However, despite some promising associations between polymorphisms of key players and clinical or in vitro data, little is known about which genes and factors could influence the response to the main tocolytic medications. We plan an in vitro candidate-based CRISPR screening on myometrial cell lines to identify relevant factors and ultimately build a screening strategy to allow for personalised tocolytic treatment. During this master thesis, the student would investigate how various medications affect contractions-relevant signalling pathways using various transformed human myometrial cells and an assay based on a FlexStation II Multi-Mode Microplate Reader. | Sara Caviglia, PhD / Prof Dr. phil II Ana Paula Simões-Wüst | ja | Arbeitsort: University Hospital Zurich, Department of Obstetrics Tel.: +41 44 255 51 31 | |
In vitro safety assessment of glucagon-like peptide-1 receptor agonists during pregnancy One in seven children is born with a prominent but preventable disadvantage and will have to bear - often for life - the consequences of maternal hyperglycaemia. Some of these children already suffer from metabolic disorders at birth, many will develop diabetes and obesity in the future. The number of pregnant women with hyperglycaemia is increasing, however most available medications for attaining constant blood glucose level cannot be used during pregnancy due to a lack of evidence on safety. One of such antidiabetic groups are the glucagon-like peptide-1 receptor agonists (GLP-1ra). Enteroendocrine cells of the gut control postprandial blood glucose levels by secreting GLP-1 that leads to an increase of insulin levels and a reduction of glucagon secretion. Moreover, GLP-1 inhibits gastric emptying and food absorption, maximising nutrient absorption and limiting weight gain. Several GLP-1ra have been introduced in the treatment of T2DM and more recently for weight loss. These medications do not cause hypoglycaemia and have been shown to reduce the risk of individual major adverse cardiovascular events, all-cause mortality, and worsening kidney function; safety issues comprise gastrointestinal symptoms. To date, there are no solid data on their transplacental transfer nor on their effect on placental function, making pregnancy a contraindication for the use of GLP-1ra. To assess the safety of GLP-1ra during pregnancy, we want to evaluate their influence on placental cell viability and on functionality in in vitro experiments by measuring their effect on pregnancy hormone secretion, glucose consumption, lactate production and cell differentiation. | Prof Dr. phil II Ana Paula Simões-Wüst | ja | Arbeitsort: University Hospital Zurich, Department of Obstetrics Tel.: +41 44 255 51 31 | |
No longer available Über den Tellerrand geschaut – Gurken zur Behandlung von Trockenem Auge | Zusammenarbeit von Pharmazeutischer Biologie (Prof. Olivier Potterat) und Translationaler Komplementärmedizin (Prof. Carsten Gründemann) | |||
No longer available Characterization of a tropical fruit extract as a potential new prebiotic | Prof. Olivier Potterat | ja | nein | |
No longer available Bryophyllum pinnatum in the treatment of inflammatory effects involved in preterm labour | PD Dr. phil II Ana Paula Simões-Wüst | ja | Arbeitsort: PD Dr. phil II Ana Paula Simões-Wüst UniversitätsSpital Zürich Tel.: +41 44 255 51 31 | |
No longer available Effects of standardized Ginkgo biloba extract on mitochondrial dysfunction induced by hyperphosphorylated tau | Prof. Anne Eckert | ja | Principal Investigator and working place: Professor Anne Eckert, PhD Psychiatric University Clinics (UPK Basel) Phone: 0041 61 325 5487 E-mail: anne.eckert@clutterupk.ch; anne.eckert@clutterunibas.ch Master thesis can be written in English or German | |
No longer available Analytical investigations on Bryophyllum pinnatum extracts in the context of GABAA receptor modulation | Prof. Olivier Potterat | ja | nein | |
No longer available Search for new Cas9 modulators in plant extracts | Prof. Olivier Potterat | ja | ||
No longer available Natural Products active on Musashi (MSI) | Dr. Eliane Garo | |||
No longer available Biosynthesis of bacterial tropone natural products | Prof. Robin Teufel | ja | ja | |
No longer available Search for new Cas9 modulators in plant extracts | Prof. O. Potterat | ja | ||
No longer available Natural Product active on Musashi (MSI1) | Dr. E. Garo | ja | ||
No longer available Target Identification for MAPK and ERK pathway | Dr. E. Garo | ja | ja | |
No longer available Phytochemical profile and bioactive constituents of the stinking hellebore (Helleborus foetidus) | Prof. O. Potterat | ja | ||
No longer available Metabolite profiling of Hibiscol®, a food supplement containing chokeberry and hibiscus extracts | Prof. O. Potterat | Ja | Nein | |
No longer available Isolation of bufadienolides from Bryophyllum pinnatum and B. daigremontianum | Prof. O. Potterat | ja | nein | |
No longer available Identifying Natural products inhibiting the mTOR Complex1 (mTORC1) | Dr. E. Garo | ja | nein | |
No longer available Protective effects of polyamines and/or wheat germ extract on mitochondrial activity and viability in an Alzheimer’s disease cell culture model | Prof. Anne Eckert | ja | ja |
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