22.3. 2018, Mitochondriální fyziologie

PhD Project:

Role of mitochondria in etiology of breast cancer

 

Metabolic pathways of cancer cells are often adjusted to produce energy and building material for cancer growth in order to provide clonal advantage over the normal cells. The pathways which ale very well characterized include mitochondrial pathways of glutamine, BCAA, serine, glycine and folate cycle, nucleotide synthesis, and many more (mitochondrial and extramitochondrial), including glycolysis. We study mitochondrial pathways related to glutamine catabolism in breast cancer cells by methods of cell biology, bioenergetics and metabolomics. We focus on the function of mitochondrial isocitrate dehydrogenase 2 (IDH2) and study mechanisms which regulate IDH2 towards oncometabolite 2-hydroxyglutarate (2HG) production. In principle, search for specificities in cancer metabolism provides the opportunity to find a weakness of the cancer cells with prospective translation into the clinical use.

 

Candidate’s profile (requirements): M.Sc. or equivalent in molecular biology, microbiology, (bio)chemistry or medicine; fascination by cell biology. Training in bioinformatics is an advantage.

 

Relevant publications:

 

Background levels of neomorphic 2-hydroxyglutarate facilitate proliferation of primary fibroblasts. Dvořák A, Zelenka J, Smolková K, Vítek L, Ježek P. Physiol Res. 2016

Reductive carboxylation and 2-hydroxyglutarate formation by wild-type IDH2 in breast carcinoma cells. Smolková K, Dvořák A, Zelenka J, Vítek L, Ježek P. Int J Biochem Cell Biol. 2015;65:125-33.

The Role of Mitochondrial NADPH-Dependent Isocitrate Dehydrogenase in Cancer Cells. Smolková K, Ježek P. Int J Cell Biol. 2012;2012:273947.

Sample drift correction in 3D fluorescence photoactivation localization microscopy. Mlodzianoski MJ, Schreiner JM, Callahan SP, Smolková K, Dlasková A, Santorová J, Ježek P, Bewersdorf J. Opt Express. 2011 Aug 1;19(16):15009-19.

Waves of gene regulation suppress and then restore oxidative phosphorylation in cancer cells. Smolková K, Plecitá-Hlavatá L, Bellance N, Benard G, Rossignol R, Ježek P. Int J Biochem Cell Biol. 2011 Jul;43(7):950-68.

Mitochondrial bioenergetic adaptations of breast cancer cells to aglycemia and hypoxia. Smolková K, Bellance N, Scandurra F, Génot E, Gnaiger E, Plecitá-Hlavatá L, Jezek P, Rossignol R. J Bioenerg Biomembr. 2010 Feb;42(1):55-67.

Distinctions and similarities of cell bioenergetics and the role of mitochondria in hypoxia, cancer, and embryonic development. Ježek P, Plecitá-Hlavatá L, Smolková K, Rossignol R. Int J Biochem Cell Biol. 2010 May;42(5):604-22.

 

Supervisor: Katarína Smolková, PhD.