The Shirokikh Group - Protein Biosynthesis and Homeostatic Control

We know what is encoded in our genomes by sequencing their DNA. But we lack a complete understanding of how this code is used by our cells to robustly function across minute homeostasis, development and disease. Approaching previously not well-accessible responses and metabolic adjustments of the cells based on the translation of transient ribonucleic acid (RNA; transcriptome) into proteins (protein biosynthesis), we can discover entirely new ways to master cellular behaviour, increase productive lifespan and enrich technology and society.

Our main approach is to precisely define the types of rapid cell responses by analysing the gene-specific levels of translation (decoding of the genetic RNA sequence into functional amino acid sequence of the proteins) on the background of transcription (synthesis of RNA based on DNA sequence in the genome) for each response and cell type. To achieve this, we use a suit of ‘high throughput’ RNA and protein methods of broad discovery combined with computational biology (bolstered with classical methods of biochemistry, molecular and structural biology), and create our own techniques.

Translational responses (alterations in the levels of protein synthesis from RNA) are of a highest interest to us as they provide an insight into the underexplored areas of flexibility and adaptability of life. Cells of higher eukaryotes have particularly complex and diverse mechanisms of protein synthesis control, which are embedded in many developmental and homeostatic programs of the organisms. Life-critical processes such as mechanisms of cell differentiation during embryonic development and formation of nervous system and its dynamic reprogramming (‘synaptic plasticity’) are largely defined at the level of RNA-controlled protein biosynthesis.

Dysregulated protein biosynthesis (dysregulated translation) is pertinent to a multitude of disorders. RNA-controlled protein biosynthesis also serves as the core of the cells’ metabolic regulation and maintains homeostasis and cell proliferation decisions appropriate to the external and internal environments. As such, it is critical for the rapid mitigation of stress damage, age-related diseases and cancer.

Motivated by its importance for life, we wish to investigate questions of basic biology of dynamic protein synthesis control as well as its applied health- and method-focused problems.

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Shirokikh NE, Dutikova YS, Staroverova MA, Hannan RD, Preiss T
Int J Mol Sci 2019 20(18) PMID: 31510048
Janapala Y, Preiss T, Shirokikh NE
Int J Mol Sci 2019 20(16) PMID: 31430885
Ragan C, Goodall GJ, Shirokikh NE, Preiss T
Sci Rep 2019 9(1): 2048 PMID: 30765711
Shirokikh NE, Preiss T
Wiley Interdiscip Rev RNA 2018 9(4): e1473 PMID: 29624880
Shirokikh NE, Archer SK, Beilharz TH, Powell D, Preiss T
Nat Protoc 2017 12(4): 697-731 PMID: 28253237
Archer SK, Shirokikh NE, Beilharz TH, Preiss T
Nature 2016 535(7613): 570-574 PMID: 27437580
Archer SK, Shirokikh NE, Preiss T
Curr Protoc Hum Genet 2015 85: 11.15.1- PMID: 25827346
Archer SK, Shirokikh NE, Hallwirth CV, Beilharz TH, Preiss T
RNA Biol 2015 12(3): 248-254 PMID: 25826658
Archer SK, Shirokikh NE, Preiss T
BMC Genomics 2014 15: 401 PMID: 24886553
Sogorin EA, Shirokikh NE, Ibragimova AM, Vasiliev VD, Agalarov SCh, Spirin AS
Biochemistry (Mosc) 2012 77(4): 342-345 PMID: 22809152
Agalarov SC, Sogorin EA, Shirokikh NE, Spirin AS
Biochem Biophys Res Commun 2011 404(1): 250-253 PMID: 21114960
Shirokikh NE, Agalarov SCh, Spirin AS
Biochemistry (Mosc) 2010 75(4): 405-411 PMID: 20618128
Shirokikh NE, Alkalaeva EZ, Vassilenko KS, Afonina ZA, Alekhina OM, Kisselev LL, Spirin AS
Nucleic Acids Res 2010 38(3): e15 PMID: 19910372
Shirokikh NE, Spirin AS
Proc Natl Acad Sci U S A 2008 105(31): 10738-10743 PMID: 18658239
Cheung YN, Maag D, Mitchell SF, Fekete CA, Algire MA, Takacs JE, Shirokikh N, Pestova T, Lorsch JR, Hinnebusch AG
Genes Dev 2007 21(10): 1217-1230 PMID: 17504939
Kovtun AA, Shirokikh NE, Gudkov AT, Spirin AS
Biochem Biophys Res Commun 2007 358(1): 368-372 PMID: 17482561
Lomakin IB, Shirokikh NE, Yusupov MM, Hellen CU, Pestova TV
EMBO J 2006 25(1): 196-210 PMID: 16362046
Fekete CA, Applefield DJ, Blakely SA, Shirokikh N, Pestova T, Lorsch JR, Hinnebusch AG
EMBO J 2005 24(20): 3588-3601 PMID: 16193068
Pisarev AV, Shirokikh NE, Hellen CU
C R Biol 2005 328(7): 589-605. PMID:15992743