Research group for molecular biology and nanomedicine

The research activities of the Molecular Biology and Nanomedicine have multidisciplinary foundations, deriving their potency from the combination of synthetic chemistry, biochemistry, nanotechnology, medicine, molecular and cellular biology plus immunology. In the sense of specific focus the group is further divided into five labs.

Výzkumná skupina molekulární biologie a nanomedicíny

The essential working philosophy resides in the identification of molecular mechanisms that are responsible for the development of oncological diseases (in particular prostate tumour, breast tumour and neurobastoms), their seriousness or the origin of chemo-resistance, with the following design and testing of functional nanoscopic modalities in vitro and in vivo. In the same way also bacterial infections are studied, and namely with primary focus upon resistant/multi-resistant bacterial stems occurring both in human and in veterinary medicine. Special highlight is reserved to the understanding of the fate of nanomaterials, both on the cellular level and on that of tissues and organisms, with substantial overlap into the domain of nanotoxicology.


doc. Mgr. Zbyněk Heger, PhD.

Head – Research group for molecular biology and nanomedicine
Assistant Professor


Phone: +420 545 133 285
Address: ÚCB AF, Zemědělská 1, 61300 Brno – Building D
Office: BA02N2004
Email:
Researcher ID: D-1973-2013
ORCID: 0000-0002-3915-7270


Team members

Topics of Ph.D. theses

  • Optional topic
  • Free topic – if interested, contact the head of the research group
  • Study of microbiome in healthy and mastitis cows
  • Free topic – immobilization of enzymes
  • Mechanism of bacterial resistance to antimicrobial nanomaterials
  • Influence of metallic and semi-metallic nanomaterials on the development of bacterial resistance
  • Nanomaterials and new types of antimicrobials as an alternative to antibiotic preparations

Projects

  • 2021/2024 – AZV ČR: Ferritin as a tool for enzymes-directed prodrug activation
  • 2019/2021 – GAČR, Encapsulation of cholinesterase reactivators using apoferritin for enhanced bioavailability in central nervous system
  • 2018/2020 – GAČR, Comprehensive insight into mechanisms of action and metabolism of tyrosine kinase inhibitors and a study of ways increasing their antitumor efficiency

  • 2019/2021 – DFG-GAČR, Zinek-dependentní signalizace a exprese sub/isoforem metalothioneinu v karcinomu prsu: implikace pro prognostické a terapeutické účely

  • 2018/2022 – Towards the Understanding a Metal-Tumor Metabolism, ERC Starting Grant, ERC-2017-STG

  • 2014/2015 – Kombinovaná terapie nádorů plic založená na chytrých nanotechnologiích, Liga proti rakovině Praha

  • 2015/2016 – Epidemiologický screening sarkosinu v moči a jeho využití pro včasnou diagnostiku nádorů prostaty, Liga proti rakovině Praha

  • 2016/2017 – Enzymy metabolismu sarkosinu a jejich vliv na proliferaci a agresivitu maligních a benigních prostatických buněk, Liga proti rakovině Praha

  • 2017/2019 – GAČR, Construction of modified apoferritin nanocarriers bearing anticancer drugs and study of mechanisms enhancing their efficiency in anticancer therapy

  • 2016 / 2018 – GAČR, The study of sarcosine metabolism and its participation in prostate cancer development

  • 2015/2019 – AZV, Influence of metallothionein on binding of platinum cytostatics to DNA in cancer cells

  • 2015/2016 – H2020-JTI-IMI2-2014-02-single, Ultra-Fast Molecular Filovirus Diagnostics „FILODIAG“, IMI2-2014-02-05

  • 2014/2016 – GAČR, Vývoj nanočástic obsahujících cytostatika a enzymy pro zlepšení chemoterapie lidských neuroblastomů a studium mechanismu jejich působení

 

Publications

  • HADDAD, H.; REMES, M.; ADAM, V.; HEGER, Z. Toward structure-based drug design against the epidermal growth factor receptor (EGFR). Drug Discov. Today, 2021, vol. 26. p. 289-295. ISSN 1359-6446. IF 7.851
  • RESSNEROVA, A.; NOVOTNY, F.; MICHALKOVA, H.; PUMERA, M.; ADAM, V.; HEGER, Z. Efficient protein transfection by swarms of chemically powered plasmonic virus-sized nanorobots. ACS Nano, 2021, vol. 15. p. 12899-12910. ISSN 1936-0851. IF 15.881
  • HAMEDUH, T.; MOKRY, M.; MILLER, A. D.; ADAM, V.; HEGER, Z.; HADDAD, Y. A rotamer relay information system in the epidermal growth factor receptor–drug complexes reveals clues to new paradigm in protein conformational change. Comp. Struct. Biotechnol. J., 2021, vol. 19. p. 5443-5454. ISSN 2001-0370. IF 7.271
  • HOFMANN, T.; ALBERT, L.; NEMETH, L.; VRSANSKA, M.; SCHLOSSEROVA, N.; VOBERKOVA, S.; VISI-RAJCZI, E. Antioxidant and antibacterial properties of Norway Spruce (Picea abies H. Karst.) and Eastern Hemlock (Tsuga canadensis (L.) Carrière) cone extracts. Forests, 2021, vol. 12. p. 1-23. ISSN 1999-4907. IF 2.633
  • ASSERGHINE, A.; ASHRAFI, A.; MUKHERJEE, A.; PETRLAK, F.; HEGER, Z.; SVEC, P.; RICHTERA, L.; NAGY, L.; SOUTO, R. M.; NAGY, G.; ADAM, V. In situ investigation of the cytotoxic and interfacial characteristics of titanium when galvanically coupled with magnesium using scanning electrochemical microscopy. ACS Appl. Mater. Interfaces, 2021, vol. 13. p. 43587-43596. ISSN 1944-8244. IF 9.229
  • HRAZDILOVA, K.; LESICZKA, P. M.; BARDON, J.; VYROUBALOVA, S.; SIMEK, B.; ZUREK, L.; MODRY, D. Wild boar as a potential reservoir of zoonotic tick-borne pathogens. Ticks Tick-Borne Dis., 2021, vol. 12. p. 1-6. ISSN 1877-9603. IF 3.744
  • JAKLOVA, K.; FEGLAROVA, T.; REX, S.; HEGER, Z.; ECKSCHLAGER, T.; HRABETA, J.; HODEK, P.; KOLARIK, M.; INDRA, R. Apoferritin/Vandetanib Association Is Long-Term Stable But Does Not Improve Pharmacological Properties of Vandetanib. Int. J. Mol. Sci., 2021, vol. 22. p. 1-12. ISSN 1422-0067. IF 5.923
  • MASARYK, L.; TESAROVA, B.; CHOQUESILLO-LAZARTE, D.; MILOSAVLJEVIC, V.; HEGER, Z.; KOPEL, P. Structural and biological characterization of anticancer nickel(II) bis(benzimidazole) complex J. Inorg. Biochem., 2021, vol. 217. p. 1-10. ISSN 0162-0134. IF 4.155
  • MERLOS, M. A. R.; MICHALKOVA, H.; STRMISKA, V.; CASAR, B.; CRESPO, P.; DE LOS RIOS, V.; CASAL, J. I.; HADDAD, H.; GURAN, R.; ECKSCHLAGER, T.; POKORNA, P.; HEGER, Z.; ADAM, V. Metallothionein-3 promotes cisplatin chemoresistance remodelling in neuroblastoma. Sci. Rep., 2021, vol. 11. p. 1-14. ISSN 2045-2322. IF 4.379
  • MERLOS, M. A. R.; CASAR, B.; MICHALKOVA, H.; JIMENEZ JIMENEZ, A. M.; HEGER, Z.; ADAM, V. Extending the applicability of In ovo and ex ovo chicken chorioallantoic membrane assays to study cytostatic activity in neuroblastoma cells. Front. Oncol., 2021, vol. 11. p. 1-10. ISSN 2234-943X. IF 6.244
  • PERIS-DIAZ, M. D.; GURAN, R.; ZITKA, O.; ADAM, V.; KREZEL, A. Mass spectrometry-based structural analysis of cysteine-rich metal-binding sites in proteins with MetaOdysseus R software. J. Proteome Res., 2021, vol. 20. p. 776-785. ISSN 1535-3893. IF 4.466
  • SKUBALOVA, Z.; REX, S.; SUKUPOVA, M.; ZAHALKA, M.; SKLADAL, P.; PRIBYL, J.; MICHALKOVA, H.; WEERASEKERA, A.; ADAM, V.; HEGER, Z. Passive diffusion vs. active pH-dependent encapsulation of tyrosine kinase inhibitors vandetanib and lenvatinib into folate-targeted ferritin delivery system. Int. J. Nanomed., 2021, vol. 16. p. 1-14. ISSN 1178-2013. IF 6.400
  • SMIDOVA, V.; MICHALEK, P.; GOLIASOVA, Z.; ECKSCHLAGER, T.; HODEK, P.; ADAM, V.; HEGER, Z. Nanomedicine of tyrosine kinase inhibitors. Theranostics, 2021, vol. 11. p. 1546-1567. ISSN 1838-7640. IF 11.556
  • STEPANKOVA, H.; SWIATKOWSKI, M.; KRUSZYNSKI, R., .; SVEC, P.; MICHALKOVA, H.; SMOLIKOVA, V.; RIDOSKOVA, A.; SPLICHAL, Z.; MICHALEK, P.; RICHTERA, L.; KOPEL, P.; ADAM, V.; HEGER, Z.; REX, S. The anti-proliferative activity of coordination compound-based ZnO nanoparticles as a promising agent against triple negative breast cancer cells. Int. J. Nanomed., 2021, vol. 2021. p. 4431-4449. ISSN 1178-2013. IF 6.400
  • MUCHOVA, J.; HEARNDEN, V.; MICHLOVSKA, L.; VISTEJNOVA, L.; ZAVADAKOVA, A.; SMERKOVA, K.; KOCIOVA, S.; ADAM, V.; KOPEL, P.; VOJTOVA, L. Mutual influence of selenium nanoparticles and FGF2‑STAB® on biocompatible properties of collagen/chitosan 3D scaffolds: in vitro and ex ovo evaluation. J. Nanobiotechnol., 2021, vol. 19. p. 1-16. ISSN 1477-3155. IF 10.435
  • Tesarova, B.Dostalova, S.Smidova, V.Goliasova, Z.Skubalova, Z.Michalkova, H.; Hynek, D.; Michalek, P.; Polanska, H.; Vaculovicova, M.; Hacek, J.; Eckschlager, T.; Stiborova, M.; Pires, A. S.; Neves, A. R. M.; Abrantes, A. M.; Rodrigues, T.; Matafome, P.; Botelho, M. F.; Teixeira, P.; Mendes, F.; Heger, Z.; Surface-PASylation of ferritin to form stealth nanovehicles enhances in vivo therapeutic performance of encapsulated ellipticine. Appl. Mater. Today, 2020, 18, art. no. 100501. DOI: 10.1016/j.apmt.2019.100501.
  • Michalkova, H.Skubalova, Z.; Sopha, H.; Strmiska, V.Tesarova, B.Dostalova, S.; Svec, P.; Hromadko, L.; Motola, M.; Macak, J. M.; Adam, V.; Heger, Z.; Complex cytotoxicity mechanism of bundles formed from self-organised 1-D anodic TiO2 nanotubes layers. J. Hazard. Mater. 2020, 388, art. no. 122054. DOI: 10.1016/j.jhazmat.2020.122054.

  • Moulick, A.; Heger, Z.; Milosavljevic, V.; Richtera, L.; Barroso-Flores, J.; Rodrigo, M. A. M.Buchtelova, H.; Podgajny, R.; Hynek, D.; Kopel, P.; Adam, V.; Real-time visualization of cell membrane damage using gadolinium-Schiff base complex-doped quantum dots. ACS Appl. Mater. Interfaces, 2018, 10, 35859-35868. DOI: 10.1021/acsami.8b15868.

  • Dostalova, S.; Polanska, H.; Svobodova, M.; Balvan, J.; Krystofova, O.; Haddad, Y.Krizkova, S.; Masarik, M.; Eckschlager, T.; Stiborova, M.; Heger, Z.; Adam, V.; Prostate-specific membrane antigen-targeted site-directed antibody-conjugated apoferritin nanovehicle favorably influences in vivo side effects of doxorubicin. Sci. Rep. 2018, 8, art. no. 8867. DOI: 10.1038/s41598-018-26772-z.

  • Buchtelova, H.Strmiska, V.Skubalova, Z.Dostalova, S.Michalek, P.; Krizkova, S.; Hynek, D.; Kalina, L.; Richtera, L.; Moulick, A.; Adam, V.; Heger, Z.; Improving cytocompatibility of CdTe quantum dots by Schiff-base-coordinated lanthanides surface doping. J. Nanobiotechnol. 2018, 16, art. no. 43. DOI: 10.1186/s12951-018-0369-7.

  • Villa, K.; Krejcova, L.; Novotny, F.; Heger, Z.; Sofer, Z.; Pumera M.; Cooperative multifunctional self-propelled paramagnetic microrobots with chemical handles for cell manipulation and drug delivery. Adv. Funct. Mater. 2018, 28, art. no. 1804343. DOI: 10.1002/adfm.201804343.

  • Smidova, V.Michalek, P.Goliasova, Z.; Eckschlager, T.; Hodek, P.; Adam, V.; Heger, Z.; Nanomedicine of tyrosine kinase inhibitors. Theranostics, 2021, 11(4), 1546-1567. DOI: 10.7150/thno.48662.

  • Tesarova, B.; Musilek, K.; Rex, S.Heger, Z.; Taking advantage of cellular uptake of ferritin nanocages for targeted drug delivery. J. Control. Release, 2020, 325, 176-190. DOI: 10.1016/j.jconrel.2020.06.026.

  • Strmiska, V.; Michalek, P.; Lackova, Z.; Guran, R.; Krizkova, S.; Vanickova, L.; Zitka, O.; Stiborova, M.; Eckschlager, T.; Klejdus, B.; Pacik, D.; Tvrdikova, E.; Keil, C.; Haase, H.; Adam, V.; Heger, Z.; Sarcosine is a prostate epigenetic modifier that elicits aberrant methylation patterns through the SAMe-Dnmts axis. Mol. Oncol. 2019, 13, 1002-1017. DOI: 10.1002/1878-0261.12439.
  • Khezri,; Mousavi, S. M. B.; Krej; Heger,; Sofer,; Pumera; Ultrafast Electrochemical Trigger Drug Delivery Mechanism for Nanographene Micromachines. Adv. Funct. Mater. 2019, 29, 1-10. DOI: 10.1002/adfm.201806696.
  • Bytesnikova, Z.; Richtera, L.; Smerkova, K.; Adam, V.; The graphene oxide as a tool for antibiotic resistance genes removal: A review. Environ. Sci. Pollut. Res. 2019, 26, 20148-20163. DOI: 10.1007/s11356-019-05283-y.
  • Skubalova, Z.; Michalkova, H.; Michalek, P.; Strmiska, V.; Guran, R.; Merlos, M. A. R.; Castkova, K.; Hynek, D.; Pekarik, V.; Zitka, O.; Adam, V.; Heger, Z.; Prevalent anatase crystalline phase increases the cytotoxicity of biphasic titanium dioxide nanoparticles in mammalian cells. Colloid Surf. B-Biointerfaces 2019, 182, 1-10. DOI: 1.
  • Strmiska, V.; Michalek, P.; Eckschlager, T.; Stiborova, M.; Adam, V.; Krizkova, S.; Heger, Z.; Prostate cancer-specific hallmarks of amino acids metabolism: Towards a paradigm of precision medicine. Biochim. Biophys. Acta-Rev. Cancer 2019, 1871, 248-258. DOI: 10.1016/j.bbcan.2019.01.001.
  • Haddad, Y.; Adam, V.; Heger, Z.; Rotamer dynamics: analysis of rotamers in molecular dynamics simulations of proteins . Biophys. J. 2019, 116, 2062-2072. DOI: 10.1016/j.bpj.2019.04.017.
  • Vanickova, L.; Guran, R.; Kollar, S.; Emri, G.; Krizkova, S.; Do, T.; Heger, Z.; Zitka, O.; Adam, V.; Mass spectrometric imaging of cysteine rich proteins in human skin. Int. J. Biol. Macromol. 2019, 125, 270-277. DOI: 10.1016/j.ijbiomac.2018.11.272.
  • Tesarova, B.; Charousova, M.; Dostalova, S.; Bienko, A.; Kopel, P.; Kruszynski, R.; Hynek, D.; Michalek, P.; Eckschlager, T.; Stiborova, M.; Adam, V.; Heger, Z.; Folic acid-mediated re-shuttling of ferritin receptor specificity towards a selective delivery of highly cytotoxic nickel(II) coordination compounds. Int. J. Biol. Macromol. 2019, 126, 1099-1111. DOI: 10.1016/j.ijbiomac.2018.12.128.
  • Peskova, M.; Ilkovics, L.; Hynek, D.; Dostalova, S.; Sanchez-Carnerero; Remes, M.; Heger, Z.; Pekarik, V.; Detergent-modified catalytic and enzymomimetic activity of silver and palladium nanoparticles biotemplated by Pyrococcus furiosus ferritin. J. Colloid Interface Sci. 2019, 537, 20-27. DOI: 10.1016/j.jcis.2018.11.005.
  • Jelinkova, P.; Mazumdar, A.; Sur, V. P.; Kociova, S.; Dolezelikova, K.; Jimenez Jimenez, A. M.; Koudelkova, Z.; Mishra, P. K.; Smerkova, K.; Heger, Z.; Vaculovicova, M.; Moulick, A.; Adam, V.; Nanoparticle-drug conjugates treating bacterial infections. J. Control. Release 2019, 307, 166-185. DOI: 10.1016/j.jconrel.2019.06.013.
  • Buchtelova, H.; Skubalova, Z.; Strmiska, V.; Michalek, P.; Kociova, S.; Smerkova, K.; Kruszynski,; Bienko,; Kaj,; Lewinska,; Bienko,; Malik-Gajewska,; Milosavljevic,; Kopel,; Heger,; Adam, V.; Synthesis and structural characterization of antimicrobial binuclear copper (II) coordination compounds bridged by hydroxy- and/or thiodipropionic acid. J. Inorg. Biochem. 2019, 191, 8-20. DOI: 10.1016/j.jinorgbio.2018.10.011.
  • Ananbeh, H. A. A. A.; Stojanovic, M.; Pompeiano, A.; Voberkova, S.; Trasar-Cepeda, C.; Use of soil enzyme activities to assess the recovery of soil functions in abandoned coppice forest systems. Sci. Total Environ. 2019, 694, art. no. 133692. DOI: https://doi.org/10.1016/j.scitotenv.2019.133692.
  • Jimenez Jimenez, A. M.; Moulick, A.; Bhowmick, S.; Strmiska, V.; Gagic, M.; Horakova, Z.; Kostrica, R.; Masarik, M.; Heger, Z.; Adam, V.; One-step detection of human papilloma viral infection using quantum dot-nucleotide interaction specificity. Talanta 2019, 205, 1-8. DOI: 10.1016/j.talanta.2019.07.006.
  • Indra, R.; Cerna, T.; Heger, Z.; Hrabeta, J.; Wilhelm, M.; Dostalova, S.; Lengalova, A.; Martinkova, M.; Adam, V.; Eckschlager, T.; Schmeiser, H. H.; Arlt, V. M.; Stiborova, M.; Ellipticine-loaded apoferritin nanocarrier retains DNA adduct-based cytochrome P450-facilitated toxicity in neuroblastoma cells. Toxicology 2019, 419, 40-54. DOI: 10.1016/j.tox.2019.03.009.
  • Milosavljevic, V.; Jamroz, E.; Gagic, M.; Haddad, Y.; Michalkova, H.; Balkova, R.; Tesarova, B.; Moulick, A.; Heger, Z.; Richtera, L.; Kopel, P.; Adam, V.; Encapsulation of Doxorubicin in Furcellaran/Chitosan Nanocapsules by Layer-by-Layer Technique for Selectively Controlled Drug Delivery. Biomacromolecules 2019, in press, . DOI: 10.1021/acs.biomac.9b01175 .
  • Gagic, M.; Jamroz, E.; Krizkova, S.; Milosavljevic, V.; Kopel, P.; Adam, V.; Current trends in detection of histamine in food and beverages . J. Agric. Food Chem. 2019, 67, 773-783. DOI: 10.1021/acs.jafc.8b05515.
  • Merlos, M. A. R.; Buchtelova, H.; de los Rios; Casal; Eckschlager, T.; Hrabeta, J.; Belhajova, M.; Heger, Z.; Adam, V.; Proteomic signature of neuroblastoma cells UKF-NB-4 reveals key role of lysosomal sequestration and the proteasome complex in acquiring chemoresistance to cisplatin. J. Proteome Res. 2019, 18, 1255-1263. DOI: 10.1021/acs.jproteome.8b00867 .
  • Beladi-Mousavi,; Khezri,; Krej; Heger,; Sofer,; Fisher,; Pumera; Recoverable Bismuth-Based Microrobots: Capture, Transport, and On-Demand Release of Heavy Metals and an Anticancer Drug in Confined Spaces . ACS Appl. Mater. Interfaces 2019, 11, 13359-13369. DOI: 10.1021/acsami.8b19408.
  • Horky, P.; Skalickova, S.; Urbankova, L.; Baholet, D.; Kociova, S.; Bytesnikova, Z.; Kabourkova, E.; Lackova, Z.; Cernei, N.; Gagic, M.; Milosavljevic, V.; Smolikova, V.; Vaclavkova, E.; Nevrkla, P.; Knot, P.; Krystofova, O.; Hynek, D.; Kopel, P.; Skladanka, J.; Adam, V.; Smerkova, K.; Zinc phosphate-based nanoparticles as a novel antibacterial agent: in vivo study on rats after dietary exposure. J. Anim. Sci. Biotechnol. 2019, 10, 1-12. DOI: 10.1186/s40104-019-0319-8.
  • Michalkova, H.; Strmiska, V.; Kudr, J.; Skubalova, Z.; Tesarova, B.; Svec, P.; Richtera, L.; Zitka, O.; Adam, V.; Heger, Z.; Tuning the surface coating of IONs towards efficient sonochemical tethering and sustained liberation of topoisomerase II poisons. Int. J. Nanomed. 2019, 14, 7609. DOI: 10.2147/IJN.S208810.