Michał Łaźniewski received his PhD from the Medical University of Warsaw in 2015. His thesis “Application of molecular docking and homology modelling for the structural and functional analysis of proteins” was supervised by prof. Plewczyński and prof Ginalski from the Laboratory of Bioinformatics and Systems Biology, CeNT UW. In his work, he performed an in-depth evaluation of seven molecular docking programs used in the in silico drug design process. He analyzed both the ability of the programs to recreate the correct conformation of protein-ligand complexes and to predict their binding strength. Additionally, he worked on predicting the structure and function of selected proteins (like the protein encoded by the C16orf57 gene) and whole protein families (DUF2319). In 2015 he became a post-doc in prof. Plewczyński’s Laboratory of Functional and Structural Genomics. There he worked on predicting the host tropism for the influenza virus based on the binding energy of the hemagglutinin protein and selected sialic acids. This work was a part of the OPUS grant 'Virtual High Throughput Screening (vHTS) derivation of a cross-immunity model for the Influenza-A Virus Infections'. Furthermore, using molecular dynamics simulations, he studied the role of mutations in proteins like PARS2, COL12A1 or TWINKLE in the development of genetic disorders. Recently, his main focus is the role of CTCF protein in the establishment of genome 3D structures, especially in the context of the heritability of DNA loops. In 2019 with the support from the NCN grant "MINIATURA", he visited the Ruan Lab in the Jackson Laboratory, USA.
I plan to focus my work on two areas. First is the bioinformatic analysis of the Spike proteins from the Coronavirdae family. My goal is to identify the novel strains from this family that can jump from bats, the predominant hosts of Coronavirdae, to humans. This project is supported by the IDUB against COVID-19 grant „Bat Coronaviruses as an emerging threat for the human population”. Two main actions are planned. Initially, using neural networks novel predictor for identifying interacting proteins will be proposed. The training phase will occur in two steps. First, a more general predictor will be proposed design to identify the interacting protein. In the second step, using transfer learning, the predictor will be retrained to better distinguish interacting viral proteins. With this approach, I will determine which Coronaviridae species can recognize human proteins. Finally, the results will be validated by calculated the free energy of binding of selected proteins. The free energy itself will be calculated using the MM-PBSA and PMF methods. The molecular dynamics simulations will be performed using either available crystal structures of proteins or the proposed homology models. My second area of interest is the 3D structure of the human genome from both healthy and sick subjects. Recent research highlights its role in the development of genetic disorders as equally important as other DNA features, like histone modifications, single nucleotide polymorphism or structural variants. The introduction of new methods to identify the genome 3D structure demands a careful comparison of new and previously obtained data. In my work, I focus on understanding the heritability of DNA loops in various populations from all over the world. To that end, I plan to analyze the results of the genetic experiment (Hi-C, GAM, ChIA-PET) released by the 4DN consortium. Additionally, the introduction of new long-read sequencing methods adds a new level of complexity to the genetic analysis. The long-read methods, despite their generally lower quality, can be used in areas in which the short-read method seems insufficient. One such area is the identification of structural variants. Thus, I plan to identify a collection of structural variants observed in human populations using the Oxford Nanopore sequencing data. Combining information obtained with both sequencing technologies seems to be an obvious next step in analyzing genomic data.
- Lazniewski, M., K. Steczkiewicz, L. Knizewski, I. Wawer, and K. Ginalski. "Novel Transmembrane Lipases of Alpha/Beta Hydrolase Fold." FEBS Lett 585, no. 6 (Mar 23 2011): 870-4. http://dx.doi.org/10.1016/j.febslet.2011.02.016.
- Plewczynski, D., M. Lazniewski, R. Augustyniak, and K. Ginalski. "Can We Trust Docking Results? Evaluation of Seven Commonly Used Programs on Pdbbind Database." J Comput Chem 32, no. 4 (Mar 2011): 742-55. http://dx.doi.org/10.1002/jcc.21643.
- Plewczynski, D., M. Lazniewski, M. von Grotthuss, L. Rychlewski, and K. Ginalski. "Votedock: Consensus Docking Method for Prediction of Protein-Ligand Interactions." J Comput Chem 32, no. 4 (Mar 2011): 568-81. http://dx.doi.org/10.1002/jcc.21642.
- Nowosielski, M., M. Hoffmann, L. S. Wyrwicz, P. Stepniak, D. M. Plewczynski, M. Lazniewski, K. Ginalski, and L. Rychlewski. "Detailed Mechanism of Squalene Epoxidase Inhibition by Terbinafine." J Chem Inf Model 51, no. 2 (Feb 28 2011): 455-62. http://dx.doi.org/10.1021/ci100403b.
- Mroczek, S., J. Krwawicz, J. Kutner, M. Lazniewski, I. Kucinski, K. Ginalski, and A. Dziembowski. "C16orf57, a Gene Mutated in Poikiloderma with Neutropenia, Encodes a Putative Phosphodiesterase Responsible for the U6 Snrna 3' End Modification." Genes Dev 26, no. 17 (Sep 01 2012): 1911-25. http://dx.doi.org/10.1101/gad.193169.112.
- Saha, I., B. Rak, S. S. Bhowmick, U. Maulik, D. Bhattacharjee, U. Koch, M. Lazniewski, and D. Plewczynski. "Binding Activity Prediction of Cyclin-Dependent Inhibitors." J Chem Inf Model 55, no. 7 (Jul 27 2015): 1469-82. http://dx.doi.org/10.1021/ci500633c.
- Huang, R., Z. A. Ripstein, R. Augustyniak, M. Lazniewski, K. Ginalski, L. E. Kay, and J. L. Rubinstein. "Unfolding the Mechanism of the Aaa+ Unfoldase Vat by a Combined Cryo-Em, Solution Nmr Study." Proc Natl Acad Sci U S A 113, no. 29 (Jul 19 2016): E4190-9. http://dx.doi.org/10.1073/pnas.1603980113.
- Mazzocco, G., M. Lazniewski, P. Migdal, T. Szczepinska, J. P. Radomski, and D. Plewczynski. "3dflu: Database of Sequence and Structural Variability of the Influenza Hemagglutinin at Population Scale." Database (Oxford) 2016 (2016). http://dx.doi.org/10.1093/database/baw130.
- Kulecka, M., A. Wierzbicka, A. Paziewska, M. Mikula, A. Habior, W. Janczyk, M. Dabrowska, J. Karczmarski, M. Lazniewski, K. Ginalski, A. Czlonkowska, P. Socha, and J. Ostrowski. "A Heterozygous Mutation in Got1 Is Associated with Familial Macro-Aspartate Aminotransferase." J Hepatol 67, no. 5 (Nov 2017): 1026-30. http://dx.doi.org/10.1016/j.jhep.2017.07.003.
- Lazniewski, M., W. K. Dawson, T. Szczepinska, and D. Plewczynski. "The Structural Variability of the Influenza a Hemagglutinin Receptor-Binding Site." Brief Funct Genomics (Dec 13 2017). http://dx.doi.org/10.1093/bfgp/elx042.
- Dawson, W. K., M. Lazniewski, and D. Plewczynski. "Rna Structure Interactions and Ribonucleoprotein Processes of the Influenza a Virus." Brief Funct Genomics (Oct 10 2017). http://dx.doi.org/10.1093/bfgp/elx028.
- Oldak, M., D. Ozieblo, A. Pollak, I. Stepniak, M. Lazniewski, U. Lechowicz, K. Kochanek, M. Furmanek, G. Tacikowska, D. Plewczynski, T. Wolak, R. Ploski, and H. Skarzynski. "Novel Neuro-Audiological Findings and Further Evidence for Twnk Involvement in Perrault Syndrome." J Transl Med 15, no. 1 (Feb 08 2017): 25. http://dx.doi.org/10.1186/s12967-017-1129-4.
- Chlebowska-Tuz, J., O. Sokolowska, P. Gaj, M. Lazniewski, M. Firczuk, K. Borowiec, H. Sas-Nowosielska, M. Bajor, A. Malinowska, A. Muchowicz, K. Ramji, P. Stawinski, M. Sobczak, Z. Pilch, A. Rodziewicz-Lurzynska, M. Zajac, K. Giannopoulos, P. Juszczynski, G. W. Basak, D. Plewczynski, R. Ploski, J. Golab, and D. Nowis. "Inhibition of Protein Disulfide Isomerase Induces Differentiation of Acute Myeloid Leukemia Cells." Haematologica (Jul 12 2018). http://dx.doi.org/10.3324/haematol.2018.190231.
- Ciara, E., D. Rokicki, M. Lazniewski, H. Mierzewska, E. Jurkiewicz, M. Bekiesinska-Figatowska, D. Piekutowska-Abramczuk, K. Iwanicka-Pronicka, E. Szymanska, P. Stawinski, J. Kosinska, A. Pollak, M. Pronicki, D. Plewczynski, R. Ploski, and E. Pronicka. "Clinical and Molecular Characteristics of Newly Reported Mitochondrial Disease Entity Caused by Biallelic Pars2 Mutations." J Hum Genet (Feb 6 2018). http://dx.doi.org/10.1038/s10038-017-0401-z.
- Lazniewski, M., W. K. Dawson, A. M. Rusek, and D. Plewczynski. "One Protein to Rule Them All: The Role of Ccctc-Binding Factor in Shaping Human Genome in Health and Disease." Semin Cell Dev Biol (Oct 11 2018). http://dx.doi.org/10.1016/j.semcdb.2018.08.003.
- Marusiak, A. A., M. K. Prelowska, D. Mehlich, M. Lazniewski, K. Kaminska, A. Gorczynski, A. Korwat, O. Sokolowska, H. Kedzierska, J. Golab, W. Biernat, D. Plewczynski, J. Brognard, and D. Nowis. "Upregulation of Mlk4 Promotes Migratory and Invasive Potential of Breast Cancer Cells." Oncogene (Dec 14 2018). http://dx.doi.org/10.1038/s41388-018-0618-0.
- Jezela-Stanek, A., A. Walczak, M. Lazniewski, J. Kosinska, P. Stawinski, V. Murcia Pienkowski, A. Biernacka, M. Rydzanicz, G. Kostrzewa, P. Krajewski, D. Plewczynski, and R. Ploski. "Novel Col12a1 Variant as a Cause of Mild Familial Extracellular Matrix-Related Myopathy." Clin Genet (Mar 28 2019). http://dx.doi.org/10.1111/cge.13534.
- Dawson, W. K., M. Lazniewski and D. Plewczynski "Free energy-based model of CTCF-mediated chromatin looping in the human genome." Methods.( 6 Jul 2020), https://doi.org/10.1016/j.ymeth.2020.05.025