Alexander Mankin
Distinguished Professor, Pharmaceutical Sciences and Center for Biomolecular Sciences
Contact
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900 S. Ashland Ave, Rm. 3052, Chicago, IL
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About Heading link
Overview:
The research in Mankin/Vázquez-Laslop lab is aimed on understanding fundamental mechanisms of protein synthesis and antibiotic action.
The ribosome has the ability to monitor the sequence of the polypeptides it makes. It can recognize and respond to specific nascent peptide sequences. Functional interactions between the ribosome and the nascent peptide are used for the regulation of gene expression and may also facilitate protein folding and targeting. We are investigating the molecular mechanisms of nascent peptide-sensing by the ribosome and studying the ribosomal response to regulatory sequences in the nascent peptides.
Many antibiotics interfere with bacterial growth by inhibiting protein synthesis. However, the mechanisms of action of many antibiotics are unknown or unclear. We have recently found that many ribosome-targeting antibiotics inhibit protein synthesis in a context-specific manner arresting translation only at specific mRNA sites. We are exploring what distinguishes the sites of preferential drug action and what cryptic features of translation could be exposed context specificity of antibiotics.
The ability to modify and expand the ribosome functionality is one of the main tasks of synthetic biology. We are using the current knowledge of the ribosome structure and function to engineer altered ribosomal RNA designs to enable properties unattainable for the ‘native’ ribosome.
Research Interests:
Fundamental mechanisms of protein synthesis. Structure and function of the ribosome. Ribosome engineering. Mechanisms of antibiotic action. Mechanisms of resistance to antibiotics.
Teaching Statement:
Mechanisms of antibiotic action and resistance.
Bacterial genomics in the age of next-generation DNA sequencing.
Mechanisms of protein synthesis and gene expression.
Approaches for studying gene expression and mechanisms of antibiotic action.
Teaching and Supervision Heading link
PSCI Ph.D. Thesis Research (PSCI 599), 8/26/2024 – 12/6/2024
PSCI Ph.D. Thesis Research (PSCI 599), 6/10/2024 – 8/2/2024
PhD Thesis Research (BCMG 599), 6/10/2024 – 8/2/2024
PSCI Ph.D. Thesis Research (PSCI 599), 1/8/2024 – 4/26/2024
PSCI 541 Pharmaceutical Applications of Genomics and Bioinformatics (PSCI 541), 8/22/2023 – Present
PSCI Ph.D. Thesis Research (PSCI 599), 8/21/2023 – 12/1/2023
PhD Thesis Research (BCMG 599), 6/12/2023 – 8/4/2023
BCMG 575: Topics in Biochemistry and Molecular Genetics (BCMG 575), 2/23/2023 – Present
MIM 560: Microbial Pathogenesis (MIM 560), 2/7/2023 – Present
Selected Grants
Engineering a fully-integrated translation system for production of proteins and peptides, National Science Foundation., 6/15/2024 - 5/31/2028, Obligated Amount: $543105; Anticipated Amount: $724140
Unraveling context specificity of translation by elucidating the mechanism of action of auxiliary translation factors, National Institutes of Health., 12/1/2023 - Present, No Obligated Amount Set; Anticipated Amount: $3175340
Determining the mechanism and impact of streptococcal RaS-RiPPs on the human oral microbiome, National Institutes of Health (National Institute of Dental and Craniofacial Research)., 8/1/2023 - 7/31/2025, Obligated Amount: $111701; Anticipated Amount: $223402
Antibiotics targeting translation, McMaster University., 6/1/2023 - 11/30/2023, Obligated Amount: $50000; Anticipated Amount: $50000
Precise Combination Strategies Targeting Carbapenem-Resistant Klebsiella pneumoniae, National Institutes of Health (National Institute of Allergy and Infectious Diseases)., 12/5/2022 - 11/30/2027, Obligated Amount: $1512796; Anticipated Amount: $3660946
Advancing ribosome-targeting antibacterial peptides with a unique mechanism of action, NIH/NIAID., 2/8/2022 - 1/31/2027, Obligated Amount: $454250; Anticipated Amount: $3299182
Advancing ribosome-targeting antibacterial peptides with a unique mechanism of action, NIH/NIAID., 2/8/2022 - 1/31/2027, Obligated Amount: $454250; Anticipated Amount: $3299182
Advancing ribosome-targeting antibacterial peptides with a unique mechanism of action, NIH/NIAID., 7/16/2021 - 2/7/2022, Obligated Amount: $730027; Anticipated Amount: $730027
Advancing ribosome-targeting antibacterial peptides with a unique mechanism of action, NIH/NIAID., 7/16/2021 - 2/7/2022, Obligated Amount: $730027; Anticipated Amount: $730027
Selected Publications
Koller, Timm O, Berger, Max J, Morici, Martino, Paternoga, Helge, Bulatov, Timur, Di Stasi, Adriana, Dang, Tam, Mainz, Andi, Raulf, Karoline, Crowe-McAuliffe, Caillan, Scocchi, Marco, Mardirossian, Mario, Beckert, Bertrand, Vázquez-Laslop, Nora, Mankin, Alexander S, Süssmuth, Roderich D, Wilson, Daniel N. (2024). Paenilamicins are context-specific translocation inhibitors of protein synthesis. Nature Chemical Biology, 1-10. doi:10.1038/s41589-024-01752-9.
★ Vazquez-Laslop, Nora, Sharma, Cynthia M, Mankin, Alexander, Buskirk, Allen R. (2022). Identifying Small Open Reading Frames in Prokaryotes with Ribosome Profiling. Journal of Bacteriology, 204, (1), e00294-e00221. doi:10.1128/jb.00294-21.
★ Svetlov, Maxim S, Syroegin, Egor A, Aleksandrova, Elena V, Atkinson, Gemma C, Gregory, Steven T, Mankin, Alexander S, Polikanov, Yury S. (2021). Structure of Erm-modified 70S ribosome reveals the mechanism of macrolide resistance. Nature Chemical Biology, 17, (4), 412-420. doi:10.1038/s41589-020-00715-0.
★ Baliga, Chetana, Brown, Tyler J, Florin, Tanja, Colon, Sarah, Shah, Vallari, Skowron, Kornelia J, Kefi, Amira, Szal, Teresa, Klepacki, Dorota, Moore, Terry W, Vázquez-Laslop, Nora, Mankin, Alexander S. (2021). Charting the sequence-activity landscape of peptide inhibitors of translation termination. Proceedings of the National Academy of Sciences of the United States of America, 118, (10), e2026465118. doi:10.1073/pnas.2026465118.
★ Meydan, Sezen, Marks, James, Klepacki, Dorota, Sharma, Virag, Baranov, Pavel V, Firth, Andrew E, Margus, Tōnu, Kefi, Amira, Vázquez-Laslop, Nora, Mankin, Alexander S. (2019). Retapamulin-Assisted Ribosome Profiling Reveals the Alternative Bacterial Proteome. Molecular Cell, 74, (3), 481-493.e6. doi:10.1016/j.molcel.2019.02.017.
★ Meydan, Sezen, Vázquez-Laslop, Nora, Mankin, Alexander S. (2018). Genes within Genes in Bacterial Genomes. Microbiology Spectrum, 6, (4), 10.1128/microbiolspec.rwr-0020-2018. doi:10.1128/microbiolspec.rwr-0020-2018.
★ Vázquez-Laslop, Nora, Mankin, Alexander S. (2014). Triggering Peptide-Dependent Translation Arrest by Small Molecules: Ribosome Stalling Modulated by Antibiotics. Regulatory Nascent Polypeptides. (pp. 165-186). Springer Nature. doi:10.1007/978-4-431-55052-5_10.
★ Mangano, Kyle, Florin, Tanja, Shao, Xinhao, Klepacki, Dorota, Chelysheva, Irina, Ignatova, Zoya, Gao, Yu, Mankin, Alexander S, Vázquez-Laslop, Nora. Genome-wide effects of the antimicrobial peptide apidaecin on translation termination in bacteria. eLife, 9, e62655. doi:10.7554/elife.62655.
★ Svetlov, Maxim S, Koller, Timm O, Meydan, Sezen, Shankar, Vaishnavi, Klepacki, Dorota, Polacek, Norbert, Guydosh, Nicholas R, Vázquez-Laslop, Nora, Wilson, Daniel N, Mankin, Alexander S. Context-specific action of macrolide antibiotics on the eukaryotic ribosome. Nature Communications, 12, (1), 2803. doi:10.1038/s41467-021-23068-1.
Professional Leadership
NIH Conflict Grant Study Section, National Institutes of Health, 12/16/2022 - Present
SURF students conference judge, University of Illinois at Chicago, 8/6/2021 - Present
Interview with Dr. Kochlar, Science historian (phage therapy), University of Illinois at Chicago, 11/19/2019 - Present
Hosting students and postdocs from Northwestern U (Jewett lab) to train in ribosome techniques, Northwestern University, 10/1/2019 - Present
Hosting joint lab meeting with Dr. Wolfe (Loyola University) to discuss their researh, Loyola University Chicago, 7/3/2019 - Present
Education
Degrees:
PhD, Moscow State University, Russian Federation
DSci, Moscow State University, Russian Federation