Dr Gracjan Michlewski

Personal Profile

Gracjan Michlewski is a Senior Lecturer (Zhejiang) in Biomedical Sciences at The University of Edinburgh. He obtained his PhD and Habilitation from the Institute of Bioorganic Chemistry, Polish Academy of Sciences in Poznan, Poland. Gracjan has been a postdoctoral fellow in the Human Genetics Unit, Medical Research Council in Edinburgh. In 2011, he established his laboratory at The Wellcome Trust Centre for Cell Biology, University of Edinburgh with Medical Research Council Career Development Award.

Research

Gracjan’s main research interests are associated with regulation of gene expression, RNA processing and innate immune response to RNA viruses. He discovered a number of factors and mechanisms that regulate production of miRNAs (short non-coding RNAs that control physiological and pathological gene expression pathways). He demonstrated that E3 ubiquitin ligase TRIM25 (a key player in innate immune response to RNA viruses) is a novel RNA-binding protein. Finally, Gracjan showed that Oleic Acid (a natural ω-9 monounsaturated fatty acid produced by various plants and animal cells) directly stimulates the production of tumour suppressor miRNA. His findings have far reaching consequences for our understanding of how RNA-binding proteins and metabolites regulate gene expression, RNA processing and innate immunity.

Research Themes

• Host-Pathogen Interactions
• Systems Biology/Big Data

Teaching

Gracjan is involved in developing and delivering undergraduate and postgraduate teaching at the Zhejiang University-University of Edinburgh Institute.

ZJU-UoE Institute

Funding

• Wellcome
• Moray Fund

Group Members

• Dr Gracjan Michlewski– Principal Investigator
• Dr Nila Roy Choudhury – Postdoctoral Associate
• Laura Croenen - PhD Student

Collaborations

• Alfredo Castello/Oxford University
• Atlanta Cook/University of Edinburgh
• Paul Digard/ University of Edinburgh
• Sander Granneman/ University of Edinburgh
• Yael Nossent/ Leiden University
• Andres Ramos/UCL
• Juri Rappsilber/University of Edinburgh
• Suzan Rosser/University of Edinburgh
• Michael Sattler/Munich Technical University
• Maryia Trubitsyna/University of Edinburgh

Recent publications

Kooshapur, H., Choudhury, N.R., Simon, B., Mühlbauer, M., Jussupow, A., Fernandez, N., Jones, A.N., Dallmann, A., Gabel, F., Camilloni, C., Michlewski, G*., Caceres, J.F*., and Sattler, M*. Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1. (2018) Nat Commun. 2018 9:2479 (* - co-corresponding)

Choudhury, N.R., and Michlewski, G. Quantitative identification of proteins that influence miRNA biogenesis by RNA pull-down-SILAC mass spectrometry (RP-SMS). (2018) Methods 18:30052-5.

Choudhury, NR., Heikel, G., Trubitsyna, M., Kubik, P., Nowak, JS., Webb, S., Granneman, S., Spanos, C., Rappsilber, J., Castello, A., and Michlewski, G. RNA-binding activity of Trim25 is mediated by its PRY/SPRY domain and is required for ubiquitination. (2017) BMC Biology 15:105

Kumar, S*., Downie Ruiz Velasco, A*., and Michlewski, G. Oleic Acid induces miRNA-7 processing through remodeling of pri-miRNA-7/protein complex. (2017) J Mol Biol 11:1638-1649 (*-equal contribution)

Nowak, J.S., Hobor, F., Downie Ruiz Velasco, A., Choudhury, N.R., Heikel, G., Kerr, A., Ramos, A., and Michlewski, G. Lin28a uses distinct mechanisms of binding to RNA and affects positively and negatively miRNA levels. (2017) RNA 3:317-332

Choudhury, N.R., Nowak, J.S., Zuo J., Rappsilber, J., Spoel H.S., and Michlewski, G. Trim25 is an RNA-specific activator of Lin28a/TuT4-mediated uridylation. (2014) Cell Rep. 4:1265-72.

Nowak, J.S., Choudhury, N.R., de Lima Alves, F., Rappsilber, J., and Michlewski, G. Lin28a regulates neuronal differentiation and inhibits miR-9 processing. (2014) Nat Commun. 5:3687

Choudhury, N.R., de Lima Alves, F., de Andrés-Aguayo, L., Graf, T., Cáceres, J.F., Rappsilber, J., and Michlewski, G. Tissue-specific control of brain-enriched miR-7 biogenesis. (2013) Genes Dev. 27: 24-38. Evaluated by Faculty of 1000 Biology

Michlewski, G., and Cáceres, J.F. Antagonistic role of hnRNP A1 and KSRP in the regulation of Let-7a biogenesis. (2010) Nat Struct Mol Biol. 17, 1011-1018. Evaluated by Faculty of 1000 Biology

Michlewski, G*., Guil, S*., Semple, C.A., and Cáceres, J.F. (2008) Posttranscriptional regulation of miRNAs harboring conserved terminal loops. Mol Cell. 32, 383-93. (*-equal contribution). Evaluated by Faculty of 1000 Biology