Aktuelle Masterarbeitsthemen der Forschungsgruppe Pharmazeutische Biologie
Current Master's Theses-Projects of the Research Group in Pharmaceutical Biology

 

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MSc PharmazieMSc Drug SciencesBemerkungen
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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 SchäferneinjaThis 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 GaroneinjaThis 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 Teufeljaja 

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
Ruminants, phytochemical composition, alpine natural grassland plants, animal nutrition, veterinary medicine

Florian Leiber und Michael Walkenhorstja 

 

No longer available

Bryophyllum pinnatum in the treatment of inflammatory effects involved in preterm labour

PD Dr. phil II Ana Paula Simões-Wüstja 

Arbeitsort:

PD Dr. phil II Ana Paula Simões-Wüst
Forschungsgruppenleiterin

UniversitätsSpital Zürich
Forschung Geburtshilfe
Schmelzbergstrasse 12 /PF 125 Path G 51a
8091 Zürich

Tel.: +41 44 255 51 31
E-Mail: anapaula.simoes-wuest(at)usz.ch

No longer available

Effects of standardized Ginkgo biloba extract on mitochondrial dysfunction induced by hyperphosphorylated tau

Prof. Anne Eckertja 

Principal Investigator and working place:

Professor Anne Eckert, PhD
Head, Neurobiology Laboratory for Brain Aging and Mental Health

Psychiatric University Clinics (UPK Basel)
Wilhelm Klein Strasse 27
CH-4002 Basel, Switzerland

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 Potteratjanein 

No longer available

Search for new Cas9 modulators in plant extracts

Prof. Olivier Potteratja  

No longer available

Natural Products active on Musashi (MSI)

Dr. Eliane Garo   

No longer available

Biosynthesis of bacterial tropone natural products

Prof. Robin Teufeljaja 

No longer available

Search for new Cas9 modulators in plant extracts

Prof. O. Potteratja  

No longer available

Natural Product active on Musashi (MSI1)

Dr. E. Garoja  

No longer available

Target Identification for MAPK and ERK  pathway

Dr. E. Garojaja 

No longer available

Phytochemical profile and bioactive constituents of the stinking hellebore (Helleborus foetidus)

Prof. O. Potteratja  

No longer available

Metabolite profiling of Hibiscol®, a food supplement containing chokeberry and hibiscus extracts

Prof. O. PotteratJaNein 

No longer available

Isolation of bufadienolides from Bryophyllum pinnatum and B. daigremontianum

Prof. O. Potteratjanein 

No longer available

Identifying Natural products inhibiting the mTOR Complex1 (mTORC1) 

Dr. E. Garojanein 

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 Eckertjaja