DiSC(3) jako nástroj pro studium MDR pump v rezistentních rakovinových buňkách
| Thesis title in Czech: | DiSC(3) jako nástroj pro studium MDR pump v rezistentních rakovinových buňkách |
|---|---|
| Thesis title in English: | DiSC(3) as the tools for the study the MDR pumps activity in cancer drug resistant cells |
| Key words: | P-glycoprotein,MDR pumps, cancer cells, fluorescence |
| English key words: | P-glykoproteín, MDR pumpy, rakovinové buňky, fluorescence |
| Academic year of topic announcement: | 2015/2016 |
| Thesis type: | Bachelor's thesis |
| Thesis language: | |
| Department: | Institute of Physics of Charles University (32-FUUK) |
| Supervisor: | RNDr. Ĺuboslava Buriánková, Ph.D. |
| Author: |
| Guidelines |
| Hlavním cílem navrhované práce je najít, či vybrané fluorescenční sonda DiSC3(3) je substrátem pro P-glykoprotein, co je MDR pumpa zodpovědná za mnohočetní lékovou rezistenci rakovinových buněk vůči lékům. Dále bude monitorovaný P-glykoprotein pro aplikaci různých chemických stresorů. Částkové úkoly bakalářské práce budou:
1. Zpracovat literární přehled o problematice rezistentních rakovinových buňek 2.Zpracovat literární přehled o problematice fluorescenčních sond využívaných ke studiu aktivity MDR pump 3. Osvojit si fundamentální laboratorní zručnosti v laboratoři buňkových kultur 4. Osvojit si experimentální techniku fluorescenční spektroskopie a průtokové cytometrie při měření aktivity MDR pump pomocí fluorescenčních sond. 5.Určit zda je DiSC3(3) substrátem pro P-glykoprotein. |
| References |
| •Szakacs G. et al.: Targeting multidrug resistance in cancer, Nature reviews Drug discovery (2006) 5:219-234
•Sarkadi B. et al.: Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system, Physiol Rev. (2006) 86: 1179–123 •Plášek J, Sigler K: Slow fluorescent indicators of membrane potential: A survey of different approaches to probe response analysis, J. Photochem. Photobiol. B-Biology, (1996) 33: 101-124 •Gottesman M. et al.: P-glycoprotein and multidrug resitance, Cur. Opinion in Gen.&Dev. (1996) 6: 610-617 |
| Preliminary scope of work in English |
| Although the term multidrug resistance has been known for more than two decades and even P-glycoprotein coding genes were identified ten years ago, the action of efflux pumps and their biological function is still not clearly understood. Methods for real-time monitoring of MDR pump activity are rarely available.
The particular aims of the proposed project deal with very current topic, as the fluorescence assay allows to establish kinetic characterization of medically attractive MDR-pump action in cells treated and non-treated with chemical stressors and/or pumps´ inhibitors as well as finding new MDR inhibitors. The developed fluorescence assay can help solve the cells´ response on anticancer drugs, antibiotics, fungicides, herbicides, etc... Results obtained from proposed project could be applied for determination of MDR pump activity of mammalian cells, especially cancer cell lines displaying high resistance to treatment and the selective accumulation of drug. Even the higher effectiveness of treatment can be achieved by finding new delivery system for anticancer cell drugs. |