Dr Nikolay Shirokikh

NHMRC Emerging Leadership Fellow
College of Health & Medicine

From 1997-2003 Nikolay Shirokikh studied Biochemistry and Molecular Biology at the M.V. Lomonosov Moscow State University (Moscow, Russia). In 2004, he worked on the mechanisms defining start codon selection fidelity during his postgraduate internship in the laboratory of Profs Pestova and Hellen (State University of New York, Brooklyn, NY, USA). In 2011, he completed his PhD in the laboratory of Prof Spirin (Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, Russia), where he investigated unusual properties of viral mRNA leaders that define their ability to 'hijack' ribosomes and overtake the host protein synthesis.

In 2012, he was awarded Go8 European Fellowship (The Group of Eight Universities, Australia) to collaborate with the RNA Biology Laboratory headed by Prof Preiss for an innovative project on the mechanisms of eukaryotic translation initiation. From 2015, he worked in the Preiss group where he primarily used high-throughput sequencing methods to explore functions of eukaryotic RNA in live cells. Together with Prof Preiss and Dr Archer, he has created an approach allowing to dissect all translation control in vivo (translation complex profile sequencing, TCP-seq).

In 2019, Nikolay Shirokikh was awarded an NHMRC Emerging Leadership Investigator Grant to expand the research of rapid translational control in the areas of cell stress response and cancer biology.

Research interests

Dr Nikolay Shirokikh is a biochemist and molecular biologist interested in mechanisms underlying the decoding of genetic information. Instructions on how, when and where to make proteins to fulfil the ever-changing requirements of the living cells are encoded in the ribonucleic acid messages (messenger(m)RNA). Translation of mRNA into protein is central to all life. Mechanisms regulating translation are important for cell survival and wellbeing.

In eukaryotic cells, where production of each type or variant of protein can be individually regulated, translational control is especially complex. Control of protein synthesis is directly involved in the processes critical for multicellular eukaryotes, such as cell differentiation, synaptic plasticity, adaptation and pro- and counter-survival decision making of the somatic and germline cells. Malignant cells utilise alternative translation pathways to survive and escape treatment through drug resistance.

The primary interest of Dr Shirokikh is to obtain deep knowledge of eukaryotic translation that will allow to decipher, and eventually manipulate, the mRNA regulatory elements responsible for mRNA-wise regulation of protein synthesis. Dr Shirokikh has a particular interest and expertise in mammalian translation, but also works with yeast when accessibility of genetics is necessary. He uses a variety of molecular biology, biophysics, biochemistry and genetics approaches applied to synthetic systems that model in vivo molecular interactions, and also works directly with live cells. He is currently using high-throughput RNA sequencing methods to obtain the new knowledge of how different eukaryotic mRNAs can control their translation.

  • Shirokikh, N, Dutikova, Y et al 2019, 'Migration of Small Ribosomal Subunits on the 5' Untranslated Regions of Capped Messenger RNA', International Journal of Molecular Sciences, vol. 20, no. 18. pp. 4464
  • Shirokikh, N & Preiss, T 2018, 'Cover Image, Volume 9, Issue 4 WIREs RNA', Wiley Interdisciplinary Reviews: RNA
    , vol. 9, no. 4.
  • Shirokikh, N & Preiss, T 2018, 'Translation initiation by cap-dependent ribosome recruitment: Recent insights and open questions', Wiley Interdisciplinary Reviews: RNA
    , vol. 9, no. 4, pp. e1473 (1-45).
  • Shirokikh, N, Archer, S, Beilharz, T et al 2017, 'Translation complex profile sequencing to study the in vivo dynamics of mRNA-ribosome interactions during translation initiation, elongation and termination', Nature Protocols, vol. 12, no. 4, pp. 697-731.
  • Archer, S•, Shirokikh, N•, Beilharz, T et al 2016, 'Dynamics of ribosome scanning and recycling revealed by translation complex profiling', Nature, vol. 535, no. 7613, pp. 570-574.
  • Archer, S•, Shirokikh, N• & Preiss, T 2015, 'Probe-directed degradation (PDD) for flexible removal of unwanted cDNA sequences from RNA-seq libraries', in A. Boyle, J.L Haines, B. R Korf (ed.), Current Protocols in Human Genetics, John Wiley & Sons Inc., New Jersey, USA, pp. 11.15.1-11.15.36.
  • Sogorin, E, Shirokikh, N, Ibragimova, A et al 2012, 'Leader sequences of eukaryotic mRNA can be simultaneously bound to initiating 80S ribosome and 40S ribosomal subunit', Biochemistry. Biokhimiia, vol. 77, no. 4, pp. 342-345.
  • Agalarov, S, Sogorin, E, Shirokikh, N et al 2011, 'Insight into the structural organization of the omega leader of TMV RNA: The role of various regions of the sequence in the formation of a compact structure of the omega RNA', Biochemical and Biophysical Research Communications, vol. 404, no. 1, pp. 250-253.
  • Shirokikh, N, Alkalaeva, E, Vassilenko, K et al 2010, 'Quantitative analysis of ribosome-mRNA complexes at different translation stages', Nucleic Acids Research, vol. 38, no. 3, pp. e15-e15.
  • Shirokikh, N, Agalarov, S & Spirin, A 2010, 'Chemical and enzymatic probing of spatial structure of the omega leader of tobacco mosaic virus RNA', Biochemistry. Biokhimiia, vol. 75, no. 4, pp. 405-411.