Dr Olga Makarova

My scientific development has taken place by carrying out research in prominent labs around the world. First as a research assistant at then Leningrad Nuclear Physics Institute in the laboratory of molecular and radiation biophysics. Then I was fortunate to join the lab of Morton Bradbury at the UC Davis where I worked on chromatin reconstitution for neutron scattering analysis (1991-93). My next achievement in the lab of Marc Dreyfus at ‘Ecole Normale Superieure’ in Paris (1993-94) was investigating the coupling between transcription and translation in bacteria. In 1994-97 I was exploring the mechanism of splice site selection by competing RNA-binding proteins SRSF1 and hnRNPA1 under the supervision of Ian Eperon at the University of Leicester. From 1997 until 2004 I was working in the lab of Reinhard Luhrmann in Marburg Institute for Molecular Biology and Tumour Research of Philipps University and later in Gottingen Max-Plank-Institute for Biophysical Chemistry. There I have identified and characterised several spliceosomal proteins and used EM to look at the purified complexes. In 2004 I have moved to Leicester and started my own research in splicing. 

My research is focused on the mechanism of splicing and the proteins involved in the early steps of spliceosome assembly. Introns invaded the genome of eukaryotes early in evolution that caused the interruption of protein coding sequences as compared with prokaryotes. Interestingly eukaryotic cells invented the mechanism to remove introns from RNA transcripts and the splicing machinery is conserved. In higher eukaryotes there is a widespread phenomenon of alternative splicing when the removal of introns goes differently and this phenomenon correlates with the complexity of organisms and is extremely observed in neurones in the brain.

Understanding how introns are recognised and spliced out is a big task as there are many RNA-binding proteins that are involved. Also in humans introns are much bigger than the coding regions exons. The question in place how the splice sites are coming in proximity.

Also it was discovered that splicing process causes diseases either due to mutations in splicing signals or factors that are involved.

My main focus is on PRPF40 and STAR proteins and their role in splicing and cancer progression.

The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure Robert E. Turnbull Louise Fairall Almutasem Saleh Emma Kelsall Kyle L. Morris T. J. Ragan Christos G. Savva Aditya Chandru Christopher J. Millard Olga V. Makarova Corinne J. Smith Alan M. Roseman Andrew M. Fry Shaun M. Cowley John W. R. Schwabe Nat Commun. 2020; 11: 3252. Published online 2020 Jun 26. doi: 10.1038/s41467-020-17078-8 PMCID: PMC7319964

The 35S U5 snRNP Is Generated from the Activated Spliceosome during In vitro Splicing Olga V. Makarova Evgeny M. Makarov PLoS One. 2015; 10(5): e0128430. Published online 2015 May 28. doi: 10.1371/journal.pone.0128430 PMCID: PMC4447412

Functional mammalian spliceosomal complex E contains SMN complex proteins in addition to U1 and U2 snRNPs Evgeny M. Makarov Nicholas Owen Andrew Bottrill Olga V. Makarova Nucleic Acids Res. 2012 Mar; 40(6): 2639-2652. Published online 2011 Nov 21. doi: 10.1093/nar/gkr1056 PMCID: PMC3315330

Isoforms of U1-70k Control Subunit Dynamics in the Human Spliceosomal U1 snRNP Helena Hernández Olga V. Makarova Evgeny M. Makarov Nina Morgner Yutaka Muto Daniel Pomeranz Krummel Carol V. Robinson PLoS One. 2009; 4(9): e7202. Published online 2009 Sep 28. doi: 10.1371/journal.pone.0007202 PMCID: PMC2747018

A subset of human 35S U5 proteins including Prp19 function prior to catalytic step 1 of splicing Makarova OV. Makarov EM. Urlaub H. Will CL. Gentzel M. Wilm M. and Lührmann R. The EMBO Journal. 2004; 23(12): pp. 2381-2391. ISSN: 0261-4189

Three-dimensional structure of a pre-catalytic human spliceosomal complex B Boehringer D. Makarov EM. Sander B. Makarova OV. Kastner B. Lührmann R. and Stark H. Nature Structural & Molecular Biology. 2004; 11(5): pp. 463-468. ISSN: 1545-9993

Small Nuclear Ribonucleoprotein Remodeling During Catalytic Activation of the Spliceosome EVGENY M. MAKAROVOLGA V. MAKAROVAHENNING URLAUBMARC GENTZELCINDY L. WILLMATTHIAS WILMAND REINHARD LÜHRMANN SCIENCE. 2002 Oct; 298(5601): pp. 2205-2208. DOI: 10.1126/science.1077783

Protein 61K encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa is required for U4/U6·U5 tri-snRNP formation and pre-mRNA splicing Olga V. Makarova Evgeny M. Makarov Sunbin Liu Hans-Peter Vornlocher Reinhard Lührmann EMBO J. 2002; 21: 1148-1157. https://doi.org/10.1093/emboj/21.5.1148

The 65 and 110 kDa SR-related proteins of the U4/U6·U5 tri-snRNP are essential for the assembly of mature spliceosomes Olga V. Makarova Evgeny M. Makarov Reinhard Lührmann EMBO J. 2001; 20: 2553-2563. https://doi.org/10.1093/emboj/20.10.2553

Selection of Alternative 5′ Splice Sites: Role of U1 snRNP and Models for the Antagonistic Effects of SF2/ASF and hnRNP A1 Ian C. Eperon Olga V. Makarova Akila Mayeda Stephen H. Munroe Javier F. Cáceres Daniel G. Hayward Adrian R. Krainer Mol Cell Biol. 2000 Nov; 20(22): 8303-8318. doi: 10.1128/mcb.20.22.8303-8318.2000 PMCID: PMC102138

Transcribing of Escherichia coli genes with mutant T7 RNA polymerases: stability of lacZ mRNA inversely correlates with polymerase speed Makarova OV. Makarov EM. Sousa R. and Dreyfus M. Proceedings of the National Academy of Sciences. 1995; 92(26): pp. 12250-12254. ISSN: 0027-8424

Currently I have two projects. One is in collaboration with Cyril Dominguez a structural biologist (LISCB Leicester Institute of Structural and Chemical Biology). We aim to identify the structures and functions of the Sam68 and T-STAR proteins. This project involves isolation and characterisation of complexes associated with these proteins using mass-spectrometry and determination of their RNA targets. The isolated complexes are the subject to visualisation and structure determination using electron microscopy.

The second project is aiming to disclose the function of two human PRPF40 (A and B) prologues in cell biology and diseases. These proteins play multiple roles in cells including splicing and cytoskeletal organisation. They have been associated with diseases such as Rett syndrome Huntington disease and many cancers.

I am involved in teaching Gene Expression through out the undergraduate programme. This includes first year BS1030 lectures in Transcription and Translation. I am also involved in supervising the biochemical practicals of the module and take a part in demonstrating in the BS1040 practicals which teach microbiology technics.

I co-convene with John Schwabe the second-year module BS2091 - From Genes to Proteins - where the basic knowledge on gene expression is introduced.

I give the lectures in BS3010 (Gene expression and medical relevance) on non-coding RNA.

I am involved in teaching the MSc course in CCMB (Cancer Cell and Molecular Biology) supervising the practical on cloning.

I am confident to talk about gene expression splicing and associated disseises.