Dr Sebastian Fica

Background

Sebastian Fica was born in Romania and studied in the United States, where he received his BA in molecular biology from Skidmore College in 2007 and his PhD in cell and molecular biology from The University of Chicago in 2013. From 2014 to 2021 he pursued postdoctoral work in the laboratory of Kiyoshi Nagai at the MRC Laboratory of Molecular Biology in Cambridge, being supported by an EMBO Long Term Fellowship and a Marie Sklodowska Curie Fellowship. In 2021 he was appointed a Wellcome Trust and Royal Society Sir Henry Dale Fellow to start his independent research group in The Department of Biochemistry at Oxford University. He joined Magdalen College as a Senior Demy in 2021.

Research

Sebastian’s research focuses on the molecular mechanisms of pre-mRNA splicing. During gene expression, DNA is transcribed into pre-messenger RNAs (pre-mRNAs), which are spliced through the excision of non-coding introns to produce mature RNAs (mRNAs) with continuous protein-coding information. Introns expand proteomic diversity by allowing a single gene to encode multiple mRNA isoforms and thus multiple protein isoforms with distinct activities in specific tissues. Splicing is performed by the spliceosome – a dynamic assembly of RNA and proteins. During his postdoc, Sebastian used electron cryo-microscopy to solve some of the first high-resolution structures of the spliceosome. His Oxford group now studies how the activity and dynamics of the spliceosome are regulated to ensure correct splicing of different pre-mRNAs in specific tissues and developmental states.

Selected publications:

• Wilkinson, M. E., Fica, S. M., Galej, W. P. & Nagai, K. Structural basis for conformational equilibrium of the catalytic spliceosome. Mol Cell 81, 1–14 (2021)
• Fica, S. M. Cryo-EM snapshots of the human spliceosome reveal structural adaptions for splicing regulation. Current Opinion in Structural Biology 65, 139–148 (2020).
• Fica, S. M., Oubridge, C., Wilkinson, M. E., Newman, A. J. & Nagai, K. A human postcatalytic spliceosome structure reveals essential roles of metazoan factors for exon ligation. Science (New York, NY) 363, 710–714 (2019).
• Fica, S. M. et al. Structure of a spliceosome remodelled for exon ligation. Nature 542, 377–380 (2017).
• Fica, S. M. et al. RNA catalyses nuclear pre-mRNA splicing. Nature 503, 229–234 (2013).