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Bachelor/Master Thesis: Effect of benzimidazoles on Giardia duodenalis tubulin dynamics

Giardia duodenalis represents a group of medically important protozoan parasites that are a major cause of gastroenteritis worldwide. Treatment is well established by using for instance nitroimidazole or benzimidazole compounds. However, approximately 20% of giardiasis cases are refractory to treatment possibly due to the development of resistant parasites.

Resistance mechanisms of G. duodenalis against benzimidazoles (e.g. albendazole) are largely unknown. In other organisms such as helminths the importance of target mutations in the beta-tubulin gene for the resistance has been well documented.

In this project the function of G. duodenalis beta-tubulin will be assessed by an in vitro fluorescence microcopy based tubulin proliferation assay using tubulin flash fusion proteins. Therefore wild type and mutagenized beta-tubulin genes will be cloned and tagged with flash proteins to produce transgenic parasites expressing tubulin-flash protein variants. Recombinant tubulin will be purified and assessed in an in vitro assay using confocal (TIRF) microscopy. The candidate will learn classical molecular biological methods including cloning of genes in appropriate vector systems in E. coli and G. duodenalis as well as high-end fluorescence microscopy techniques. The work will be performed at Robert Koch-Institute in Berlin, FG16 Mycotic and parasitic agents and mycobacteria in close collaboration with the Reber Lab of IRI for the Life Sciences at Humboldt-University Berlin.

Contact: Dr. Christian Klotz

Date: 18.12.2017