Evgeny Makarov

Academic qualifications

• PhD, Molecular Biology – Institute of Molecular Biology and Genetics, Kiev, USSR
• MSc, Biophysics – Leningrad Polytechnical University, Leningrad, USSR

Teaching responsibilities

Module co-ordinator

• BB3210 - Methods in Forensic Investigation
• BB1204 - Practical Skills in Biomedical Sciences

Other responsibilities

Academic appointments

2007: Lecturer, Division of Biosciences, School of Health Sciences and Social Care, Brunel University,

2005-2007: Research Associate, Department of Biochemistry, University of Leicester,

1998-2000: Post-doctoral researcher, Max-Planck-Institut für Biophysikalische Chemie, Göttingen, Germany.

1997-2000: Post-doctoral researcher, Institut für Molekularbiologie und Tumorforschung, Philipps-Universität, Marburg, Germany

1994 -1997: Research Associate, Department of Biochemistry, University of Leicester,UK

1993 -1994: CNRS researcher, Laboratoire de Génétique Moléculaire, Ecole Normale Supérieure, Paris, France

1991 -1993: Post-doctoral researcher, Department of Biological Chemistry, School of Medicine, University of California, Davis, USA.

1990 -1991: Post-doctoral researcher, Department of Molecular Microbiology, School of Medicine, Washington University, St. Louis, USA

1980 -1990: Research scientist, Department of Molecular and Radiation Biophysics, Leningrad Nuclear Physics Institute, Gatchina, USSR

Research interests

My research interests are in the field of precursor messenger RNA (pre-mRNA) splicing. Pre-mRNA splicing is a cellular process in which non-coding sequences (introns) are removed and coding sequences (exons) are joined together to generate mRNA for protein production. Pre-mRNA splicing is somewhat similar to film editing: if it is not done properly, two unmatched scenes may be stitched together in one episode, which would not make sense. In splicing, if exon-intron boundaries (splice sites) are not correctly identified, the wrong mRNA will be produced. From this a faulty protein will be synthesised and this may cause disease. To extend the analogy, a film scenario is dramatically changed by the selection of scenes; by the same token, in a living cell, pre-mRNA can be processed in different ways via the alternative use of different splice sites. This phenomenon is called alternative splicing and allows the production of several proteins from a single gene. I am currently focused on the study of disease-associated alternative splicing. The major ongoing project is on the study of the ageing-related pre-mRNA splicing of human LMNA gene, encoding lamin A and C proteins, and especially, its aberrant splicing that causes the premature ageing of Hutchinson Gilford Progeria Syndrome patients. The aim is to identify the proteins modulating the specific splicing outcomes which, in turn, are likely to affect the speed of the ageing process. In this respect, the pharmaceutical targeting of the proteins identified in the proposed research -- inhibition of their function by small interacting molecules -- may lead to the discovery of novel drugs capable of slowing the ageing process. The other ongoing projects are: (i) The study of SCLC (small cell lung cancer) associated alternative splicing of actinine-4 pre-mRNA; (ii) The hTERT alternative splicing regulation as a potential cancer therapeutic modality.

Research centres

• Brunel Institute for Cancer Genetics and Pharmacogenomics (BICGP)
• Centre for Cell and Chromosome Biology (CCCB)

Research projects and grants

• The Progeria Research Foundation Research Grant (2010/11)

• The Royal Society Research Grant (2008/09)

• The BRIEF (Brunel Research Initiative and Enterprise Fund) Award (2007/08)

Publications

Journal Papers

(2012) Girard, C., Will, CL., Peng, J., Makarov, EM., Kastner, B., Lemm, I., Urlaub, H., Hartmuth, K. and Lührmann, R., Post-transcriptional spliceosomes are retained in nuclear speckles until splicing completion., Nature Communications 3994

(2012) Makarov, EM., Owen, N., Bottrill, A. and Makarova, OV., Functional mammalian spliceosomal complex E contains SMN complex proteins in addition to U1 and U2 snRNPs., Nucleic Acids Research 40 (6) : 2639- 2652 Download publication

(2011) Bridger, JM., Eskiw, CH., Makarov, EM., Tree, D. and Kill, IR., Progeria Research Day at Brunel University, Nucleus 2 (6) : 1- 6

(2010) Abbaszadeh, F., Clingen, PH., Arlett, C., Plowman, PN., Bourton, EC., Themis, M., Makarov, EM., Newbold, RF., Green, MHL. and Parris, CN., A novel splice variant of the DNA-PKcs gene is associated with clinical and cellular radiosensitvity in a xeroderma pigmentosum patient, Journal of Medical Genetics 46 (11) : 1- 24 Download publication

(2009) Bujakowska, K., Maubaret, C., Chakarova, CF., Tanimoto, N., Beck, SC., Fahl, E., Humphries, MM., Kenna, PF., Makarov, E., Makarova, O., Pacquet-Durand, F., Ekström, PA., van Veen, T., Leveillard, T., Humphries, P., Seeliger, MW. and Bhattacharya, SS., Study of gene-targeted mouse models of splicing factor gene Prpf31 implicated in human autosomal dominant retinitis pigmentosa (RP), Investigative Ophthalmology and Visual Science 50 (12) : 5927- 5933

(2009) Hernández, H., Makarova, OV., Makarov, EM., Morgner, N., Muto, Y., Krummel, DP. and Robinson, CV., Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP, PLoS ONE 4 (9) : e7202 Download publication

(2006) Sander, B., Golas, MM., Makarov, EM., Brahms, H., Kastner, B., Lührmann, R. and Stark, H., Organization of core spliceosomal components U5 snRNA loop I and U4/U6 di-snRNP within U4/U6.U5 tri-snRNP as revealed by electron cryomicroscopy, Molecular Cell 24 (2) : 267- 278

(2005) Laggerbauer, B., Liu, S., Makarov, E., Vornlocher, HP., Makarova, O., Ingelfinger, D., Achsel, T. and Lührmann, R., The human U5 snRNP 52K protein (CD2BP2) interacts with U5-102K (hPrp6), a U4/U6.U5 tri-snRNP bridging protein, but dissociates upon tri-snRNP formation, RNA 11 (5) : 598- 608

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

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

(2002) Makarov, EM., Makarova, OV., Urlaub, H., Gentzel, M., Will, CL., Wilm, M. and Lührmann, R., Small nuclear ribonucleoprotein remodeling during catalytic activation of the spliceosome, Science 298 (5601) : 2205- 2208

(2002) Dellaire, G., Makarov, EM., Cowger, JJ., Longman, D., Sutherland, HG., Lührmann, R., Torchia, J. and Bickmore, WA., Mammalian PRP4 kinase copurifies and interacts with components of both the U5 snRNP and the N-CoR deacetylase complexes, Mol Cell Biol 22 (14) : 5141- 5156

(2002) Schneider, C., Will, CL., Makarova, OV., Makarov, EM. and Lührmann, R., Human U4/U6.U5 and U4atac/U6atac.U5 tri-snRNPs exhibit similar protein compositions, Molecular and Cellular Biology 22 (10) : 3219- 3229

(2002) Makarova, OV., Makarov, EM., Liu, S., Vornlocher, HP. and Lührmann, R., 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., EMBO J 21 (5) : 1148- 1157 Download publication

(2001) Makarova, OV., Makarov, EM. and Lührmann, R., The 65 and 110 kDa SR-related proteins of the U4/U6.U5 tri-snRNP are essential for the assembly of mature spliceosomes., EMBO J 20 (10) : 2553- 2563 Download publication

(2000) Makarov, EM., Makarova, OV., Achsel, T. and Lührmann, R., The human homologue of the yeast splicing factor Prp6p contains multiple TPR elements and is stably associated with the U5 snRNP via protein-protein interactions., J Mol Biol 298 (4) : 567- 575

(2000) Venables, JP., Elliott, DJ., Makarova, OV., Makarov, EM., Cooke, HJ. and Eperon, IC., RBMY, a probable human spermatogenesis factor, and other hnRNP G proteins interact with Tra2beta and affect splicing., Hum Mol Genet 9 (5) : 685- 694 Download publication

(1998) Elliott, DJ., Oghene, K., Makarov, G., Makarova, O., Hargreave, TB., Chandley, AC., Eperon, IC. and Cooke, HJ., Dynamic changes in the subnuclear organisation of pre-mRNA splicing proteins and RBM during human germ cell development., J Cell Sci 111 ( Pt 9) 1255- 1265 Download publication

(1995) Makarova, OV., Makarov, EM., Sousa, R. and Dreyfus, M., Transcribing of Escherichia coli genes with mutant T7 RNA polymerases: stability of lacZ mRNA inversely correlates with polymerase speed., Proc Natl Acad Sci U S A 92 (26) : 12250- 12254 Download publication