1988 – MSc degree, specialization in technical microbiology, Lodz University of Technology, Faculty of Biotechnology and Food Sciences, Lodz, Poland
2004 – Doctor degree, Center for Molecular and Macromolecular Sciences, Polish Academy of Sciences, Lodz, Poland
2008-2016 – Adjunct, Center for Molecular and Macromolecular Sciences, Polish Academy of Sciences, Department of Bioorganic Chemistry, Lodz, Poland
2017– present – Specialist, Centre of Molecular and Macromolecular Studies of the Polish Academy of Sciences, Department of Bioorganic Chemistry, Lodz, Poland
Foreign laboratories:
2004 – 2006 – Postdoctoral fellowship at the National Institute of Advanced Industrial Science and Technology, AIST, Gene Function Research Center, Tsukuba, Japan
Research experience and interests:
Construction of recombinant genes (full-length or fragments), mutagenesis, cloning, isolation of recombinant proteins, purification and biochemical characterization
Application of therapeutic nucleic acids, such as antisense oligonucleotides, siRNA, shRNA, ribozymes, for specific silencing of gene expression, especially genes encoding proteins involved in Alzheimer’s disease.
Rational design of siRNA, shRNA for gene-specific silencing. Application of modified DNA and RNA analogues to improve specificity and activity of nucleic acid molecular tools, allele-specific silencing of mutant genes (e.g. Psn1, Sgt 1)
Investigation of the function of sulfur- and selenium-modified nucleosides at the wobble position of transfer RNA (tRNA). Characterization of the SelU protein, the enzyme responsible for the enzymatic transformation of R5S2U®R5geS2U®R5Se2U
Studies on damage of sulfur-containing tRNAs during oxidative stress in cellular models, consequences of R5S2U desulfuration on codon-anticodon interactions and cellular processes involving tRNA
Supervision of students applying for the MSc degree:
Katarzyna Sipa (Kubiak) – master’s degree: „Construction and application of plasmids encoding short interfering RNA directed to BACE1 mRNA” carried out in 2002-2003, defended in 2003 at Lodz University of Technology, Faculty of Biotechnology and Food Sciences, Institute of Technical Biochemistry
Michał Różański – master’s degree: „Receive and primary characteristics of tRNA 2-selenouridine synthase SelU from Escherichia coli ” carried out in 2014-2015, defended in 2015 at Lodz University of Technology, Faculty of Biotechnology and Food Sciences, Institute of Technical Biochemistry
Supervision of students applying for the PhD degree:
Danuta Piotrzkowska – PhD thesis entitled „Silencing cdk2/4/6 genes with RNAi for neuroprotection”, defended in 2014 at the Center for Molecular and Macromolecular Research, Polish Academy of Sciences in Lodz. Function of co-supervisor
Patrycja Szczupak – doctoral thesis entitled „SelU protein activity in the synthesis of modified nucleosides in transfer RNAs” prepared at the Center for Molecular and Macromolecular Research, Polish Academy of Sciences in Lodz. Function of co-supervisor
Monika Turek – PhD student of prof. E. Łodyga-Chruścińska from Lodz University of Technology, who performed the experiments for her PhD thesis in the Department of Bioorganic Chemistry, CBMM, PAN. Assistance in proper planning and execution of the experiments, interpretation of the results
Justyna Borowska (Pawlak) – PhD student of prof. E. Łodyga-Chruścińska from Lodz University of Technology, who performed the experiments for her PhD thesis in the Department of Bioorganic Chemistry, CBMM, PAN. Assistance in proper planning and execution of the experiments, interpretation of the results
Supervision of students undergoing long term (2-3-months) student practices
Principal investigator in 2 projects:
· NCN project entitled „Identification of the substrate specificity of proteins of the RNA interference pathway through their interactions with chemically modified siRNAs” carried out in 2010-2013. The function of Principal Investigator
· NCN project entitled: „Study of 2-thiouridine-tRNA damage occurring in cells subjected to oxidative stress” implemented in 2017-2022. The function of Principal Investigator
Co-investigator in 7national and international projects:
· MNiSW project entitled „Biophosphates and oligonucleotides and their congeners as new generation diagnostics and drugs”, carried out in 2007-2010. The function of Co-Investigator
· MNiSW project entitled „Isolation of PS-DNA and PS-DNA /LNA phosphorothioate oligonucleotides enriched in P-diastereoisomers of Rp configuration and their application to inhibit gene expression by creating RNA/PS-DNA parallel duplexes”, carried out in 2010-2011. The function of Co-Investigator
· EraNet project NEURON /01/2009 entitled „Protection against neurodegeneration by somatic gene therapy Silencing the CDK4 and CDK6 genes through RNA interference”. European research projects on CNS neurodegenerative diseases, carried out in 2009-2012. The function of Co-Investigator
· NCN project entitled „Stereodefined phosphorothioate analogs of DNA containing inserted LNA-type nucleoside units – synthesis and properties of complexes formed with DNA and RNA templates” carried out in 2012-2015. The function of Co-Investigator
· NCN project entitled „Studies on desulfuration of 2-thiouridines associated with tRNA damage under oxidative stress”. carried out in 2012-2015. The function of Co-Investigator
· NCN project entitled „Biosynthesis of seleno-modified nucleosides in the anticodon loop of transfer ribonucleic acids. Evaluation of enzymatic transformation of 2-thiouridine to 2-selenouridine, research on the function and structure of selenouridine-tRNA synthase from E. coli„, carried out in 2015-2018. The function of Co-Investigator
· NCN project entitled „Why did Nature introduce selenium into the nucleosides in the swing position of bacterial tRNAs?”, carried out 2019-2024. The function of Co-Investigator
Papers:
Nawrot, M. Sierant, P. Szczupak, Selenium modified bacterial tRNAs. In: Sugimoto, N. (eds) Handbook of Chemical Biology of Nucleic Acids. Springer, Singapore.https://doi.org/10.1007/978-981-16-1313-5_43-1, 2023.
Szczupak P, Sierant M*, Wielgus E, Radzikowska-Cieciura E, Kulik K, Krakowiak A, Kuwerska P, Leszczynska G, Nawrot B. Escherichia coli tRNA 2-Selenouridine Synthase (SelU): Elucidation of Substrate Specificity to Understand the Role of S-Geranyl-tRNA in the Conversion of 2-Thio- into 2-Selenouridines in Bacterial tRNA. 11(9), 1522, 2022.
Szczupak P, Radzikowska-Cieciura E, Kulik K, Madaj R, Sierant M, Krakowiak A, Nawrot B. Escherichia coli tRNA 2-selenouridine synthase SelU selects its prenyl substrate to accomplish its enzymatic function. Bioorg Chem., 122:105739, 2022.
Szczupak, M. Sierant, B. Nawrot. Substrate specificity of the MBP-SelU Fusion protein (Escherichia coli tRNA 2- selenouridine synthase). FEBS Open Bio 11 (Suppl. 1) 128, 2021.
Sierant*, R. Szewczyk, K. Krolewska-Golinska, A. Dziergowska, P. Bernat, E. Sochacka, B. Nawrot. Intracellular damage of mcm5S2U-tRNA induced by oxidative stress. FEBS Open Bio 11 (Suppl. 1), 489, 2021.
Bohush, A.; Góral, A.; Sierant, M.; Nawrot, B.; Leśniak, W.; Filipek, A. Sgt1 Regulates Synuclein Subcellular Localization and Expression of Parkinson’s Disease Related Genes, PINK1 and PARK9. Biomolecules 11, 1675, 2021.
Andrzej Błauz, Błazej Rychlik, Damian Plazuk, Francesca Peccati, Gonzalo Jimenez-Ose´s, Urszula Steinke, Malgorzata Sierant, Katarzyna Trzeciak, Ewa Skorupska and Beata Miksa. Biotin-phenosafranin as a new photosensitive conjugate for targeted therapy and imaging. New J. Chem. 45, 9691-9702, 2021.
Krystyna Rozga-Wijas, Malgorzata Sierant, Daunorubicin-silsesquioxane conjugates (POSS-DAU) for theranostic drug delivery system: Characterization, biocompatibility and drug release study. Reactive and Functional Polymers 143 104332, 2019.
Szczupak, M. Sierant, B. Nawrot. Studies on transformation of 2-thiouridine to 2-selenouridine catalyzed by Escherichia coli tRNA 2-selenouridine/geranyl-2-thiouridine synthase and its analogs. FEBS OpenBio 9, S1, 190, 2019.
Sierant*, R. Szewczyk, A. Dziergowska, K. Krolewska-Golinska, E. Sochacka, B. Nawrot. Studies on the 2-thiouridine-tRNA damage induced in the Saccharomyces cerevisiae yeast cells under oxidative stress conditions. FEBS OpenBio 9, S1, 190, 2019.
Krystyna Rozga-Wijas, Malgorzata Sierant, Ewelina Wielgus, Beata J. Miksa. Polyhedral octasilsesquioxanes labelled with the photosensitive cationic phenosafranin dye as a new nanocarrier for therapy and cellular imaging. Dyes and Pigments161, 261–266, 2019.
Sierant M, Kulik K, Sochacka E, Szewczyk R, Sobczak M, Nawrot B. Cytochrome c catalyzes the hydrogen peroxide-assisted oxidative desulfuration of 2-thiouridines in transfer RNAs. Chembiochem 19, 687-695, 2018.
Dolot R, Lam CH, Sierant M, Zhao Q, Liu FW, Nawrot B, Egli M, Yang X. Crystal structures of thrombin in complex with chemically modified thrombin DNA aptamers reveal the origins of enhanced affinity. Nucleic Acids Res. 46, 4819-4830, 2018.
Sierant M, Leszczynska G, Sadowska K, Komar P, Radzikowska-Cieciura E, Sochacka E, Nawrot B. Escherichia coli tRNA 2-selenouridine synthase (SelU) converts S2U-RNA to Se2U-RNA via S geranylated-intermediate. FEBS Lett. 592(13), 2248-2258, 2018.
Malgorzata Sierant, Patrycja Komar, Rafal Szewczyk, Agnieszka Dziergowska, Elżbieta Sochacka, Barbara Nawrot. Studies on the oxidative damage of wobble 5-methylcarboxymethyl- 2-thiouridine in transfer RNAs. Acta Biochimica Polonica 65, 2, 18, 2018.
Patrycja Komar, Małgorzata Sierant, Barbara Nawrot. Escherichia coli tRNA 2-selenouridine synthase (wtSelU) and its G67E mutant (mutSelU G67E): catalysis of conversion of bacterial 2-thio-uridine-tRNA to its 2-seleno-analog. Acta Biochimica Polonica 65, 2, 18, 2018.
Sierant*, R. Szewczyk, A. Dziergowska, K. Krolewska-Golinska, E. Sochacka, B. Nawrot. Studies on the 2-thiouridine-tRNA damage induced in the Saccharomyces cerevisiae yeast cells under oxidative stress conditions. FEBS OpenBio 9, S1, 190, 2019.
Szczupak, M. Sierant, B. Nawrot. Studies on transformation of 2-thiouridine to 2-selenouridine catalyzed by Escherichia coli tRNA 2-selenouridine/geranyl-2-thiouridine synthase and its analogs. FEBS OpenBio 9, S1, 190, 2019.
Krystyna Rozga-Wijas, Malgorzata Sierant, Daunorubicin-silsesquioxane conjugates (POSS-DAU) for theranostic drug delivery system: Characterization, biocompatibility and drug release study. Reactive and Functional Polymers 143 104332, 2019.
Andrzej Błauz, Błazej Rychlik, Damian Plazuk, Francesca Peccati, Gonzalo Jimenez-Ose´s, Urszula Steinke, Malgorzata Sierant, Katarzyna Trzeciak, Ewa Skorupska and Beata Miksa. Biotin-phenosafranin as a new photosensitive conjugate for targeted therapy and imaging. New J. Chem. 45, 9691-9702, 2021.
Bohush, A.; Góral, A.; Sierant, M.; Nawrot, B.; Leśniak, W.; Filipek, A. Sgt1 Regulates Synuclein Subcellular Localization and Expression of Parkinson’s Disease Related Genes, PINK1 and PARK9. Biomolecules 11, 1675. doi.org/10.3390/biom11111675, 2021.
Sierant*, R. Szewczyk, K. Krolewska-Golinska, A. Dziergowska, P. Bernat, E. Sochacka, B. Nawrot. Intracellular damage of mcm5S2U-tRNA induced by oxidative stress. FEBS Open Bio 11 (Suppl. 1), 489, DOI: 10.1002/2211-5463.13205, 2021.
Miksa B, Sierant M, Skorupska E, Michalski A, Kazmierski S, Steinke U,Rozanski A, Uznanski P. Chlorambucil labelled with the phenosafranin scaffold as a new chemotherapeutic for imaging and cancer treatment. Colloids Surf B Biointerfaces 1;159, 820-828, 2017.
Leszczynska G, Sadowska K, Sierant M, Sobczak M, Nawrot B, Sochacka E. Reaction of S-geranyl-2-thiouracil modified oligonucleotides with alkyl amines leads to the N2-alkyl isocytosine derivatives. Org Biomol Chem. 27;15(25):5332-5336, 2017.
Sierant M, Leszczynska G, Sadowska K, Dziergowska A, Rozanski M, Sochacka E, Nawrot B. S– Geranyl-2-thiouridine wobble nucleosides of bacterial tRNAs; chemical and enzymatic synthesis of S-geranylated-RNAs and their physicochemical characterization. Nucleic Acids Res. 15;44(22):10986-10998,
Abeydeera ND, Egli M, Cox N, Mercier K, Conde JN, Pallan PS, Mizurini DM, Sierant M, Hibti FE, Hassell T, Wang T, Liu FW, Liu HM, Martinez C, Sood AK, Lybrand TP, Frydman C, Monteiro RQ, Gomer RH, Nawrot B, Yang X. Evoking picomolar binding in RNA by a single phosphorodithioate linkage. Nucleic Acids Res. 30;44(17):8052-8064,
Borowska J, Sierant M, Sochacka E, Sanna D, Lodyga-Chruscinska E. DNA binding and cleavage studies of copper(II) complexes with 2′-deoxyadenosine modified histidine moiety. J Biol Inorg Chem. 20(6), 989-1004,
Małgorzata Sierant*, Danuta Piotrzkowska and Barbara Nawrot, RNAi mediated silencing of cyclin-dependent kinases of the G1 phase slows down the cell cycle and cell apoptosis. Implications for neuroprotection in Alzheimer’s disease. Acta Neurobiol Exp 75, 36–47, 2015.
Sierant, S. Kazmierski, A. Rozanski, P. Paluch, U. Bienias and B. J. Miksa, Nanocapsules for 5-fluorouracil delivery decorated with a poly(2-ethylhexyl methacrylateco-7-(4-trifluoromethyl)coumarin acrylamide) cross-linked wall. New J. Chem. 39, 1506-1516, 2015.
Pradeep S. Pallan, Xianbin Yang, Malgorzata Sierant, Dinuka Abeydeera, Tom Hassell, Carlos Martinez, Magdalena Janicka, Barbara Nawrot and Martin Egli. Crystal structure, stability and Ago2 affinity of phosphorodithioate-modified RNAs. RSC Advances 4, 64901–64904, 2014.
Sherry Y. Wu, Xianbin Yang, Kshipra M. Gharpure, Hiroto Hatakeyama, Martin Egli, Michael H. McGuire, Archana S. Nagaraja, Takahito M. Miyake, Rajesha Rupaimoole, Chad V. Pecot, Morgan Taylor, Sunila Pradeep, Malgorzata Sierant, Cristian Rodriguez-Aguayo, Hyun J. Choi, Rebecca A. Previs, Guillermo N. Armaiz-Pena, Li Huang, Carlos Martinez, Tom Hassell, Cristina Ivan, Vasudha Sehgal, Richa Singhania, Hee-Dong Han, Chang Su, Ji Hoon Kim, Heather J. Dalton, Chandra Kovvali, Khandan Keyomarsi, Nigel A.J. McMillan, Willem W. Overwijk, Jinsong Liu, Ju-Seog Lee, Keith A. Baggerly, Gabriel Lopez-Berestein, Prahlad T. Ram, Barbara Nawrot, Anil K. Sood, 2’-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity. Nature Communications5, 3459-3478, 2014.
Xianbin Yang, Malgorzata Sierant, Magdalena Janicka, Lukasz, Peczek, Carlos Martinez, Tom Hassell, Na Li, Xi Li1, Barbara Nawrot, Synthesis and gene silencing activity of siRNA molecules containing phosphorodithioate substitutions. ACS Chem Biol. 7, 1214-1220, 2012.
Malgorzata Sierant*, Alina Paduszynska, Julia Kazmierczak-Baranska, Benedetta Nacmias, Sandro Sorbi, Silvia Bagnoli, Elzbieta Sochacka, Barbara Nawrot, Specific silencing of L392V PSEN1 mutant allele by RNA interference. International Journal of Alzheimer’s Disease, Article ID 809218, 2011, doi:10.4061/2011/809218.
Barbara Nawrot, Małgorzata Sierant, Alina Paduszynska, RNA interference of genes related to Alzheimer’s Disease. RSC Drug Discovery Series No 3, Emerging drugs and targets for Alzheimer’s disease 2, (ed. A. Martinez), chapter 26 228-268,
Malgorzata Sierant*, Milena Sobczak, Magdalena Janicka, Alina Paduszynska, Danuta Piotrzkowska, Biological and physicochemical characterization of siRNAs modified with 2’,2’-difluoro-2’-deoxycytidine (gemcitabine). New Journal of Chemistry34, 918-924, 2010.
Małgorzata Sierant, Julia Kazmierczak-Baranska, Alina Paduszynska, Aleksandra Pietkiewicz, Barbara Nawrot, Longer 19-base pair short interfering RNA duplexes rather than shorter duplexes trigger RNA interference. Oligonucleotides20(4), 199-206, 2010.
S Sutou, M Kunishi, T Kudo, K Kawano, Y Takagi, M Sierant, M Nakanishi, M Sano, M Miyagishi. Knockdown of severe acute respiratory syndrome corona virus (SARS-Cov) genes by small interfering RNA (siRNA) using siRNA expression vectors and synthetic double-stranded RNA (dsRNA) as a model for siRNA design. Genes and Environment31, 5-23,
Sierant M, Kubiak K, Kazmierczak-Baranska J, Warashina M, Kuwabara T, Nawrot B. Evaluation of BACE1 Silencing in Cellular Models. Int J Alzheimer’s Dis., 14, 2009. Article ID 257403, 2009.
Sierant M, Kubiak K, Kazmierczak-Baranska J, Paduszynska A, Kuwabara T, Warashina M, Nacmias B, Sorbi S, Nawrot B. RNA interference in silencing of genes of Alzheimer’s disease in cellular and rat brain models. Nucleic Acids Symp Ser (Oxf).(52), 41-42, 2008.
Sano M, Sierant M, Miyagishi M, Nakanishi M, Takagi Y, Sutou S. Effect of asymmetric terminal structures of short RNA duplexes on the RNA interference activity and strand selection. Nucleic Acids Res. 36, 5812-5821, 2008.
