Deadline: 18th April 2021
Bajzikova, M., Kovarova, J., Coelho, A. R., Boukalova, S., Oh, S., Rohlenova, K., Svec, D., Hubackova, S., Endaya, B., Judasova, K., Bezawork-Geleta, A., Kluckova, K., Chatre, L., Zobalova, R., Novakova, A., Vanova, K., Ezrova, Z., Maghzal, G. J., Magalhaes Novais, S., Olsinova, M., Krobova, L., An, Y. J., Davidova, E., Nahacka, Z., Sobol, M., Cunha-Oliveira, T., Sandoval-Acuna, C., Strnad, H., Zhang, T., Huynh, T., Serafim, T. L., Hozak, P., Sardao, V. A., Koopman, W. J. H., Ricchetti, M., Oliveira, P. J., Kolar, F., Kubista, M., Truksa, J., Dvorakova-Hortova, K., Pacak, K., Gurlich, R., Stocker, R., Zhou, Y., Berridge, M. V., Park, S., Dong, L., Rohlena, J. & Neuzil, J. (2018) Reactivation of Dihydroorotate Dehydrogenase-Driven Pyrimidine Biosynthesis Restores Tumor Growth of Respiration-Deficient Cancer Cells. Cell Metab. IF 20,6
Cancer cells without mitochondrial DNA (mtDNA) do not form tumors unless they reconstitute oxidative phosphorylation (OXPHOS) by mitochondria acquired from host stroma. To understand why functional respiration is crucial for tumorigenesis, we used time-resolved analysis of tumor formation by mtDNA-depleted cells and genetic manipulations of OXPHOS. We show that pyrimidine biosynthesis dependent on respiration-linked dihydroorotate dehydrogenase (DHODH) is required to overcome cell-cycle arrest, while mitochondrial ATP generation is dispensable for tumorigenesis.
Bezawork-Geleta, A., Wen, H., Dong, L., Yan, B., Vider, J., Boukalova, S., Krobova, L., Vanova, K., Zobalova, R., Sobol, M., Hozak, P., Novais, S. M., Caisova, V., Abaffy, P., Naraine, R., Pang, Y., Zaw, T., Zhang, P., Sindelka, R., Kubista, M., Zuryn, S., Molloy, M. P., Berridge, M. V., Pacak, K., Rohlena, J., Park, S. & Neuzil, J. (2018) Alternative assembly of respiratory complex II connects energy stress to metabolic checkpoints. Nat Commun, 9, 2221. IF 12,4
Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CIIlow, serves as a checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their energy utilization by modulating DNA synthesis and cell cycle progression.
Petrlova, J., Hansen, F. C., Van Der Plas, M. J. A., Huber, R. G., Morgelin, M., Malmsten, M., Bond, P. J. & Schmidtchen, A. (2017) Aggregation of thrombin-derived C-terminal fragments as a previously undisclosed host defense mechanism. Proceedings of the National Academy of Sciences of the United States of America, 114, E4213-E4222. IF 9,5
Effective control of endotoxins and bacteria is crucial for normal wound healing. Here, we show that human neutrophil elastase cleaves thrombin, generating 11-kDa thrombin-derived C-terminal peptides (TCPs), which bind to and form amorphous amyloid-like aggregates with both bacterial lipopolysaccharide (LPS) and gram-negative bacteria. Upon bacterial aggregation, recombinantly produced TCPs induce permeabilization of Escherichia coli and phagocytic uptake. We indicates the presence of TCP-LPS aggregates also under physiological conditions.
Dong, L. F., Kovarova, J., Bajzikova, M., Bezawork-Geleta, A., Svec, D., Endaya, B., Sachaphibulkij, K., Coelho, A. R., Sebkova, N., Ruzickova, A., Tan, A. S., Kluckova, K., Judasova, K., Zamecnikova, K., Rychtarcikova, Z., Gopalan, V., Andera, L., Sobol, M., Yan, B., Pattnaik, B., Bhatraju, N., Truksa, J., Stopka, P., Hozak, P., Lam, A. K., Sedlacek, R., Oliveira, P. J., Kubista, M., Agrawal, A., Dvorakova-Hortova, K., Rohlena, J., Berridge, M. V. & Neuzil, J. (2017) Horizontal transfer of whole mitochondria restores tumorigenic potential in mitochondrial DNA-deficient cancer cells. Elife, 6. IF 7,6
Generation of tumours in syngeneic mice by cells devoid of mitochondrial (mt) DNA (ρ0 cells) is linked to the acquisition of the host mtDNA. To determine whether the transfer of mtDNA involves whole mitochondria, we injected B16ρ0 mouse melanoma cells into syngeneic C57BL/6Nsu9-DsRed2 mice that express red fluorescent protein in their mitochondria. We document that mtDNA is acquired by transfer of whole mitochondria from the host animal, leading to normalisation of mitochondrial respiration.
Sobol, M., Krausova, A., Yildirim, S., Kalasova, I., Faberova, V., Vrkoslav, V., Philimonenko, V., Marasek, P., Pastorek, L., Capek, M., Lubovska, Z., Ulicna, L., Tsuji, T., Lisa, M., Cvacka, J., Fujimoto, T. & Hozak, P. (2018) Nuclear phosphatidylinositol 4,5-bisphosphate islets contribute to efficient RNA polymerase II-dependent transcription. J Cell Sci, 131. IF 4,4
This paper describes a novel type of nuclear structure - nuclear lipid islets (NLIs). They are of 40-100 nm with a lipidic interior, and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] molecules comprise a significant part of their surface. The NLI periphery is associated with Pol II transcription machinery, including the largest Pol II subunit, transcription factors and NM1 (also known as NMI), and Pol II transcription is dependent on NLI integrity.
Pastorek, L., Sobol, M. & Hozak, P. (2016) Colocalization coefficients evaluating the distribution of molecular targets in microscopy methods based on pointed patterns. Histochemistry and Cell Biology, 146, 391-406. IF 2,6
In this paper, we introduce a novel computational technique for quantifying the level of colocalization in pointed patterns. Our approach follows the idea included in the widely used Manders’ colocalization coefficients in fluorescence microscopy and represents its counterpart for electron microscopy.
Philimonenko, V. V., Philimonenko, A. A., Sloufova, I., Hruby, M., Novotny, F., Halbhuber, Z., Krivjanska, M., Nebesarova, J., Slouf, M. & Hozak, P. (2014) Simultaneous detection of multiple targets for ultrastructural immunocytochemistry. Histochem Cell Biol, 141, 229-39. IF 3,1
In this paper, we describe a novel system to detect simultaneously up to five antigens in transmission electron microscope using metal nanoparticles of different shapes conjugated to secondary antibodies.
- Up to 5 core publications recommended in MEDLINE format (including IF) produced by facility users
Malinová A, Cvačková Z, Matějů D, et al. Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones. J Cell Biol. 2017;216(6):1579-1596.
Roithová A, Klimešová K, Pánek J, et al. The Sm-core mediates the retention of partially-assembled spliceosomal snRNPs in Cajal bodies until their full maturation. Nucleic Acids Res. 2018;46(7):3774-3790.
Sobol M, Krausová A, Yildirim S, et al. Nuclear phosphatidylinositol 4,5-bisphosphate islets contribute to efficient RNA polymerase II-dependent transcription. J Cell Sci. 2018; 131, jcs211094.
Fišerová J, Efenberková M, Sieger T, et al. Chromatin organization at the nuclear periphery as revealed by image analysis of structured illumination microscopy data. J Cell Sci 2017 130: 2066-2077.
von Morgen P,Burdova K, Flower T G,et al. MRE11 stability is regulated by CK2-dependent interaction with R2TP complex. Oncogene. 2017 Aug 24; 36(34): 4943–4950.
Deadline: 18th April 2021
Planned courses in 2021.
August 22-26, 2021 - virtual meeting
11th March 2021
Series of online seminars