Centre for Bacterial Cell Biology

Staff Profile

Professor Nikolay Zenkin

Professor of Molecular Biology

Background

Current lab: 4 post-docs, 3 PhD students

CV

Full Name and Title: Nikolay Zenkin, PhD (Russian/British)

Date of birth: 26/07/1979

Place of birth: Dubna (Moscow Region), Russia

Title of current appointment: Professor of Molecular Biology; Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University

 

Education and Qualification:

1996-2001 B.A., M.S. (Biochemistry). Moscow State University (Biological Faculty, Department of Molecular Biology)

2001-2004 Ph.D. (Molecular Biology). Institute of Molecular Genetics, Moscow.

 

Appointments held:

1999-2000 Research Trainee. Engelhardt Institute of Molecular Biology, Moscow

2000-2001 Research Trainee. Institute of Molecular Genetics, Moscow

2001-2004 Ph.D. Student (Molecular Biology). Institute of Molecular Genetics, Moscow

2002-2004 Research Associate. Waksman Institute, Rutgers University, NJ

2004-2007 Post-Doctoral Research Associate. Waksman Institute, Rutgers University, NJ

2007-2009 Lecturer. Institute for Cell and Molecular Biosciences of Newcastle University.

2009-2013 Senior Lecturer. Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University.

2013-present Professor of Molecular Biology; Centre for Bacterial Cell Biology, Biosciences Institute, Newcastle University

 

Honours and Awards:

2019 - 2024 – Wellcome Trust Molecular Basis of Cell Function Expert Review Group

2020 – Wellcome Trust Investigator Award

2017 – Organiser of 29th UK RNA polymerase workshop in Newcastle University

2014 – Philip Leverhulme Prize

2014 – Newcastle University Academic Distinction Award

2014 – Organiser of 26th UK RNA polymerase workshop in Newcastle University

2014 – Fleming Prize Lecture Award

2014 – Wellcome Trust Senior Investigator Award

2006 – Manchester University Research Fellowship (declined by applicant on account of Lecturer position)

2006 – Alexander von Humboldt Foundation Research Fellowship (declined by applicant on account of Lecturer position)

 

2019 – External PhD examiner York University

2016 – External PhD examiner CNRS, Montpellier University

 

External referee for research and review papers, BBSRC, MRC, Welcome Trust, Leverhulme, Singapore NMRC research grants.

 

 

Funding (sole PI unless otherwise stated):

2020 – Wellcome Trust Investigator Award: “Coupling of transcription with other cellular processes” (PI; £2.1M)

2019 – MICA MRC Grant “Novel mode of RNA polymerase inhibition by a new natural rifamycin, which is active against rifampicin-resistant RNA polymerases and bacteria” (PI; £800K)

2019 – EPSRC Programme Grant “The Physics of Antimicrobial Resistance” (Co-I; £3.5M)

2017 – Royal Society collaborative grant (PI; £12K)

2016 – EPSRC Programme Grant “Portabolomics” (Co-I; £7.5M)

2014 – Philip Leverhulme Prize (PI; £100K)

2014 – Wellcome Trust Senior Investigator Award: “Transcription: from catalysis to cellular regulation” (PI; £1.2M)

2013 – BBSRC Research Grant: “Mechanisms of transcription termination” (PI; £ 441K)

2012 – Russian Ministry of Education and Science Research Grant ”Bioengineering of mitochondria: directed modification of protein biosynthesis in mitochondria” (PI; ~£60K)

2012 – BBSRC Research Grant: “Regulation of elongation by RNA polymerase and ribosome via intrinsic signals and transcription-translation coupling” (PI; £692K)

2010 – System Biology in Microorganisms (SysMo) Research Grant (Funded by BBSRC): “Role of transcriptional fidelity and processivity on the noise of transcription, and its consequences for phenotypic bistability in Streptococcus pneumoniae” (PI; £360K)

2008 – European Research Council Starting Grant 2007; "Mechanisms of Transcription Proofreading" (PI; EUR 1.15M)

2008 – BBSRC Research Grant; "Transcription elongation processivity: resolution of backtracked complexes " (PI; £461K)

2008 – BBSRC Research Grant; “Characterisation of novel functions of the active centre of RNA polymerase” (PI; £600K)

2007 – Royal Society Research Grant; “Investigation of cleavage reactions by RNA polymerase” (PI; £15K)

 

Competitive studentships:

2017 – EPSRC PhD studentship

2017 – BBSRC PhD studentship

2016 – MRC CASE PhD studentship

2013 – BBSRC PhD studentship

2009 – MRC PhD studentship

2008 – BBSRC PhD studentship

 

Training record:

PIs:

-Dr Yulia Yuzenkova, Royal Society University Research Fellow, Senior Lecturer, Newcastle University

-Dr Katherine James, Head of Bioinformatics, National History Museum London; Principal Fellow, Northumbria University.

Post-Docs:

-14, all (apart from two who went on to work in industry, and one for government) are continuing in academia in my or other labs (Birmingham, Edinburgh, Manchester, Copenhagen, Umea Universities).

Post-graduate Students:

-7 PhD and 1 MPhil students to completion

-currently supervise 3 and directly co-supervise 3 PhD students.

 

 

Invited speaker

 

Invited lectures in Umea, Uppsala, Groningen, York, Bristol, Moscow State Universities, and Russian Academy of Sciences

 

Federation of American Societies for Experimental Biology research conference “Mechanism & Regulation of Prokaryotic Transcription”, 2017. Saxtons River, VT, USA

Zing conference “Regulating with RNA in Bacteria and Archaea” 2015 Cancun, Mexico

Federation of American Societies for Experimental Biology research conference “Mechanism & Regulation of Prokaryotic Transcription”, 2015. Saxtons River, VT, USA

Zing conference “Nucleic Acids” 2014 Cancun, Mexico

Fleming Award Lecture, Society for General Microbiology, 2014. Liverpool, UK

Federation of American Societies for Experimental Biology research conference “Mechanism & Regulation of Prokaryotic Transcription”, 2013. Saxtons River, VT, USA

Invited Lecture. 2012. Bristol University, UK

Society for General Microbiology Spring Conference, 2012. Dublin, Ireland

Federation of American Societies for Experimental Biology research conference, “Mechanism and Regulation of Prokaryotic transcription”, 2011. Saxtons River, VT, USA

69th Harden Conference “RNAP - Structure, function and evolution of RNA polymerases”. 2010. Hinxton, Cambridge, UK

Federation of American Societies for Experimental Biology research conference “Nucleic Acid Enzymes”, 2010. Snowmass Village, Colorado, USA

Federation of American Societies for Experimental Biology research conference, “Mechanism and Regulation of Prokaryotic transcription”, 2009. Saxtons River, VT, USA

American Society for Microbiology 108th General Meeting, 2008

UK RNA polymerase workshop, York University, 2008.

Federation of American Societies for Experimental Biology research conference, “Mechanism and Regulation of Prokaryotic transcription”, 2007. Saxtons River, VT, USA (n/a)

UK RNA polymerase workshop, Imperial College of London, 2007.

Federation of American Societies for Experimental Biology research conference, “Mechanism and Regulation of Prokaryotic transcription”, 2005. Saxtons River, VT, USA

Federation of American Societies for Experimental Biology research conference “Mechanism and Regulation of Prokaryotic transcription”, 2003. Saxtons River, VT, USA

 

 

Book chapters:

Mosaei H*., Zenkin N*. (2020) Inhibition of RNA Polymerase by Rifampicin and Rifamycin-Like Molecules. EcoSal Plus. 9(1). doi: 10.1128/ecosalplus.ESP-0017-2019.

Castro-Roa D and Zenkin N. Relations Between Replication and Transcription. In: Kušić-Tišma, J, ed. Fundamental Aspects of DNA Replication. Rijeka, Croatia: InTech Open, 2011, pp.289-306

 Nechaev S., Zenkin N. and Severinov K. Regulation of RNA polymerase through its active center. In: Buc, H., and Strick, T. ed. RNA polymerases as molecular motors. Cambridge, UK: RSC Pub., 2009, pp 236-259

 

Patents:

“Compounds for treating infections caused by rifampicin-resistant bacteria”

GB Initial filing-GB201812078, PCT Filing-WO2020/021252 (https://patents.google.com/patent/WO2020021252A1/en)



Research

Molecular basis of gene expression

Transcription, copying genetic information into RNA, is the first step of gene expression. In all living organisms transcription is accomplished by conserved multi-subunit RNA polymerases, one of the most ancient enzymes on the planet. Understanding functions of RNA polymerase are essential for understanding evolution of Life of the planet. Importantly, malfunctions of RNA polymerases are linked to various human diseases including cancer and Alzheimer. Also transcription is the potent target for antimicrobials. Many mechanistic details of the functioning of RNA polymerases are not clear. Furthermore RNA polymerases are imbedded in intricate relations with other cellular machineries, such as translation in prokaryotes or replication and repair in all organisms. Regulation of these interactions is pivotal for coordination of cellular processes, correct gene expression and ultimately for survival of organisms. The mechanisms underlining these interactions and their regulation are also poorly understood.

We are investigating transcription. All possible aspects: from mechanisms of reactions and inhibition by antibiotics to regulation and interactions with other cellular machineries, such as translation, splicing and replication. We use classical biochemistry and molecular biology, structural biology, some unique experimental systems as well as novel techniques. In vitro we investigate bacterial and eukaryotic RNA polymerases I, II and III. In vivo we are focusing on bacterial transcription.

The main goal of our study is to understand how RNA polymerase evolved to the enzyme we know today, and how it functions and is regulated in the modern cells. Another important aspect of our work is to look for the ways of manipulation of RNA polymerases (such as specific inhibition) in order to control pathogenicity.

Bacterial toxin-antitoxin systems

Bacteria invented several mechanisms to fight against their enemies –bacteriophages and antibiotics. One of such systems, toxin-antitoxin (TA) systems, involves a large number of small proteins, called toxins, which reversibly target essential processes in the bacterial cell to stop these processes and bring the cell to dormancy. Such dormant cells become temporarily resistant to antibiotics (phenomenon called persistence) because antibiotic targets are temporarily non-functional in them, as well as become “not interesting” to bacteriophages, because they cannot propagate in dormant cells. There are also some other biological important phenomena, such as programmed cell death and addiction to plasmids, linked to TA systems. TA systems involve large number of activities and targets, many of which are not yet known or characterised.

We are interested in mechanistic and catalytic details of functioning of TAs and the outcomes of their action for their targets.

 

Interests:

Specific: cellular machineries working with nucleic acids.

General: molecular evolution, physics of high gravities and velocities.


Selected publications:


Harbottle J, Zenkin N*. (2020) Ureidothiophene inhibits interaction of bacterial RNA polymerase with -10 promotor element. Nucleic Acids Res. 48(14):7914-7923. doi: 10.1093/nar/gkaa591.


Stevenson-Jones F., Woodgate J., Castro-Roa D, Zenkin N*. (2020) Ribosome reactivates transcription by physically pushing RNA polymerase out of transcription arrest. Proc Natl Acad Sci U S A. pii: 201919985. doi: 10.1073/pnas.1919985117


Mosaei H., Molodtsov, V., Kepplinger B., Harbottle J., Moon C., Jeeves R., Ceccaroni L., Shin, Y., Morton-Laing S., Marrs M., Wills C., Clegg W., Yuzenkova Y., Perry J., Bacon J., Errington J., Allenby N., Hall M., Murakami K., Zenkin N*.(2018) Mode of action of Kanglemycin A, an ansamycin natural product that Is active against rifampicin-resistant Mycobacterium tuberculosis. MOLECULAR CELL 72:263

 

Forrest, D., James, K., Yuzenkova, Y., Zenkin, N*. (2017) Single-peptide DNA-dependent RNA polymerase homologous to multi-subunit RNA polymerase. NATURE COMMUNICATIONS 8:15774.

 

James, K., Gamba, P., Cockell, S.J., Zenkin, N*. (2017) Misincorporation by RNA polymerase is a major source of transcription pausing in vivo. NUCLEIC ACIDS RES 45:1105

 

van Nues, R. W., Castro-Roa, D., Yuzenkova, Y., Zenkin, N*.(2016) Ribonucleoprotein particles of bacterial small non-coding RNA IsrA (IS61 or McaS) and its interaction with RNA polymerase core may link transcription to mRNA fate. NUCLEIC ACIDS RES 44:2577

 

Castro-Roa, D., Garcia-Pino, A., De Gieter, S., van Nuland, N. A. J., Loris, R., and Zenkin, N* (2013) The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF-Tu. NATURE CHEM BIOL 9:811-7

 

Germain, E., Daniel Castro-Roa, D., Zenkin, N.*. and Gerdes, K. (2013) Molecular Mechanism of Bacterial Persistence by HipA. MOLECULAR CELL 52:248-54

 

Yuzenkova, Y., Roghanian, M., Bochkareva, A., Zenkin, N.* (2013) Tagetitoxin inhibits transcription by stabilizing pre-translocated state of the elongation complex. NUCLEIC ACIDS RES, 41:9257-65

 

Nielsen, S.U., Yuzenkova, Y., and Zenkin, N*. (2013). Mechanism of RNA polymerase III transcription termination. SCIENCE 340:1577-1580

 

Zenkin, N*. (2012). Hypothesis: emergence of translation as a result of RNA helicase evolution. J MOL EVOL 74:249-256

 

Bochkareva, A., Yuzenkova, Y., Tadigotla, V. and Zenkin, N*. (2012). Factor-independent transcription pausing caused by recognition of the RNA-DNA hybrid sequence. EMBO J 31:630-639

 

Yuzenkova, Y., Tadigotla, V.R., Severinov, K., and Zenkin, N*. (2011). A new basal promoter element recognized by RNA polymerase core enzyme. EMBO J 30:3766-3775

 

Yuzenkova Y., Zenkin N*. (2010)  Central role of the RNA polymerase trigger loop in intrinsic RNA hydrolysis PROC NATL ACAD SCI U S A 107:10878-83

 

Zenkin, N*., Yuzenkova, Y. and Severinov, K. (2006) Transcript-assisted transcriptional proofreading. SCIENCE, 313:518-20.

 

Zenkin, N*., Naryshkina, T., Kuznedelov, K. and Severinov, K. (2006) The mechanism of DNA primer synthesis by RNA polymerase. NATURE, 439:617

 

Temiakov, D., Zenkin, N. (equal contr.), Vassylyeva, M. N., Perederina, A., Tahirov, T. H., Kashkina, E., Savkina, M., Zorov, S., Nikiforov, V., Igarashi, N., Matsugaki, N., Wakatsuki, S., Severinov, K. and Vassylyev, D. G. (2005). Structural basis of transcription inhibition by antibiotic streptolydigin. MOLECULAR CELL 19:655-66.

 

Zenkin, N. and Severinov, K. (2004). The role of RNA polymerase sigma subunit in promoter-independent initiation of transcription. Proc Natl Acad Sci U S A 101, 4396-400.

 

Teaching

PhDs:

I currently supervise three and co-supervise two PhD students

Earlier I have supervised 8 PhD students and 1 MPhil student to completion.

Teaching:

“Biochemistry and Drug Targets” (BGM2037), “Proteins and Enzymes” (BGM2060), “Medical Microbiology” (MIC2026) and Molecular Microbiology (MRes module MMB8016)

Publications