Dr Pasha Baranov

Dr Pasha Baranov

LAPTI stands for LAboratory of Post-Transcriptional control and bio-Informatics. We are interested in regulation of gene expression, in particular at the post-transcriptional level. We use high-throughput experimental techniques such as ribosome profiling for obtaining genome wide information on protein synthesis. We develop computational approaches to analysis these data and design databases and visualization tools for the data exploration. We also try to decipher the molecular mechanisms of gene expression regulation. Last, but not least we are interested in alterative genetic decoding (Recoding) and evolution of the Genetic Code and protein synthesis.

Our work is supported by research grants from SFI (Science Foundation Ireland) and The Wellcome Trust. We also receive individual fellowships from Irish Research Council and EMBO (European Molecular Biology Organisation). The networking activities of LAPTI members are also supported by COST (European Cooperation in Science and Technology) action SeqAhead.

  1. Ribosome Profiling
  2. Development of Bioinformatics Resources
  3. Translation of mRNA 5’ leaders in eukaryotes
  4. Recoding

 

1. Ribosome Profiling

To analyse gene expression we use Ribosome Profiling (ribo-seq) technique. Ribosome Profiling produces density maps of ribosomes on mRNAs for the entire transcriptomes at a sub-codon resolution. The scheme below illustrates what kind of information can be obtained with various ribo-seq techniques in addition to differential gene expression analysis.

Two main ribo-seq strategies. Left part of the figure: blue arrow – ribosomes are blocked during elongation; pink arrow – ribosomes blocked during initiation. Right part of the figure illustrates how two types of ribo-seq data can be used to yield details of mRNA translation. Source: Michel & Baranov (2013) Ribosome profiling: A Hi-Def monitor for protein synthesis at the genome-wide scale. WIRES RNA 4: 473-490.

References

Michel AM, Baranov PV. Ribosome profiling: a Hi-Def monitor for proteinsynthesis at the genome-wide scale. Wiley Interdiscip Rev RNA. 2013 4:473-90.

O'Connor PB, Li GW, Weissman JS, Atkins JF, Baranov PV. rRNA:mRNA pairing alters the length and the symmetry of mRNA-protected fragments in ribosome profiling experiments. Bioinformatics. 2013 29:1488-91.

Michel AM, Choudhury KR, Firth AE, Ingolia NT, Atkins JF, Baranov PV.Observation of dually decoded regions of the human genome using ribosome profiling data. Genome Res. 2012 22:2219-29.

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2. Developent of bioinformatics resources

We want to make our work as useful as possible to as many people as feasible. For this purpose we develop computational resources that are available on-line and are free of charge. Currently the most popular resources maintained by LAPTI are GWIPS-viz browser (http://gwips.ucc.ie), DARNED (http://darned.ucc.ie) and RECODE (http://recode.ucc.ie) databases. In addition to developing stand-alone resources we make the data available through the major bioinformatics resources such as UCSC Genome Browser and Ensembl.

References

Michel AM, Fox G, Kiran AM, De Bo C, O’Connor PBF, Heaphy SM, Mullan JPA, Donohue CA, Higgins DG and Baranov PV. GWIPS-viz: development of a ribo-seq genome browser. Nucleic Acids Res 2014 in press.

Kiran AM, O'Mahony JJ, Sanjeev K, Baranov PV. Darned in 2013: inclusion of model organisms and linking with Wikipedia. Nucleic Acids Res. 2013 41:D258-61.

Antonov I, Baranov P, Borodovsky M. GeneTack database: genes with frameshifts in prokaryotic genomes and eukaryotic mRNA sequences. Nucleic Acids Res. 2013 41:D152-6.

Sharma V, Murphy DP, Provan G, Baranov PV. CodonLogo: a sequence logo-based viewer for codon patterns. Bioinformatics. 2012 28:1935-6.

Kiran A, Baranov PV. DARNED: a DAtabase of RNa EDiting in humans. Bioinformatics. 2010 26:1772-6.

Bekaert M, Firth AE, Zhang Y, Gladyshev VN, Atkins JF, Baranov PV. Recode-2: new design, new search tools, and many more genes. Nucleic Acids Res. 2010 38:D69-74.

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3. Translation of mRNA 5’ leaders in eukaryotes

We have a particular interest in understanding how translation of eukaryotic 5’ mRNA leaders effects the rate of the main mRNA protein product synthesis. According to most textbooks eukaryotic mRNAs contain single translated Open Reading Frame (ORF) surrounded by 5’ and 3’ Untranslated Terminal Regions, UTRs. The accumulating evidence disagree with such representation of eukaryotic mRNAs. Biochemistry data suggest that many translation events take place in eukaryotic 5’ mRNA leaders. Phylogenetic analysis demonstrates that some of translated features of 5’ leaders are deeply conserved, meaning that some of these biological activities are functional and evolutionary important. The figure below shows biochemical and evolutionary evidence suggesting that mRNAs of important transcription factors NPAS2 and THAP7 contain short evolutionary conserved ORFs that are extensively translated. 

Ribosome profiling and phylogenetic analysis of NPAS2 and THAP7 mRNAs reveals translation of short ORFs that are evolutionary conserved. Source: Michel et (2012) Observation of dually decoded regions of the human genome using ribosome profiling data. Genome Research, 22:2219-2229.

References

Ivanov IP, Firth AE, Michel AM, Atkins JF, Baranov PV. Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences. Nucleic Acids Res. 2011 39:4220-34.

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4. Recoding

We have long standing interests in Recoding, the process that alters the genome templated protein sequence either with mRNA editing or by the means of alternative translation mechanisms, such as ribosomal frameshifting. Certain genes use recoding as a major regulator of their expression. In such cases, the sequence signals responsible for recoding exhibit remarkable evolutionary conservation of their sophisticated organisation. This is illustrated below for ribosomal frameshifting sites from bacterial release factor 2 mRNAs.

The top part of the figure shows Sequence Logo generated for an alignment of RF2 ribosomal frameshifting sites from several bacteria. The bottom part of the figure indicates the roles of various sequence elements that they play in the execution of the frameshifting. Source: Baranov & Gurvich. Sequences promoting recoding are singular genomic elements. In Atkins, John F.; Gesteland, Raymond F. (Eds.) Recoding: Expansion of Decoding Rules Enriches Gene Expression. Springer. pp. 301-320.

References

Sharma V, Firth AE, Antonov I, Fayet O, Atkins JF, Borodovsky M, Baranov PV. A pilot study of bacterial genes with disrupted ORFs reveals a surprising profusion of protein sequence recoding mediated by ribosomal frameshifting and transcriptional realignment. Mol Biol Evol. 2011 28:3195-211.

Baranov PV, Wills NM, Barriscale KA, Firth AE, Jud MC, Letsou A, Manning G, Atkins JF. Programmed ribosomal frameshifting in the expression of the regulator of intestinal stem cell proliferation, adenomatous polyposis coli (APC). RNA Biol. 2011 8:637-47.

Atkins JF, Baranov PV. Translation: duality in the genetic code. Nature. 2007 448:1004-5.

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Current lab members

Postdoctoral Fellows

Audrey Michel

Maxim Koroteev

Research Assistant

Zena Abbas

Vimalkumar Velayudhan

Sharon O’Sullivan

Systems Administrator

James Mullan (Paddy)

PhD Students (full members)

Anjali Pai

Patrick O’Connor

Romika Kumari

Stephen Heaphy

PhD students (part members)

Ioanna Tzani (co-supervised with John Atkins)

Xiangwu Lu (co-supervised with Paul Walsh)

Honorary members

Max & Vasya

Principal Investigator

Pasha (Pavel Baranov)

 

Past Lab members

Postdoctoral Fellows

Dr Dmitry Andreev

Paul Korir

PhD students

Virag Sharma (after completing Ph.D in 2012 left to a postdoctoral position at Max Planck Institute in Dresden, Germany)

Anmol Kiran (after completing Ph.D. in 2013 left to a postdoctoral position at The Wellcome Trust campus in Malawi)

Audrey Michel (after completing Ph.D. in 2013 stayed in LAPTI)

Siobhan Cleary (co-supervised with Rosemary O’Connor).

MSc Students

Audrey Michel (2010)

Patrick O’Connor (2011)

David Murphy (2011)

Gearoid Fox (2012)

Nicole Vaughan (2012)

Claire Donohue (2013)

Prominent Undergraduates

Komal Sanjeev

John O’Mahony

Oleksandr Nychyk

Christof De Bo

O'Connor PBF, Li GW, Weissman JS, Atkins JF, Baranov PV. (2013) rRNA:mRNA pairing alters the length and the symmetry of mRNA protected fragments in ribosome profiling experiments. Bioinformatics, 29:1488-1491.

Kiran A, O'Mahony J, Sanjeev K, Baranov PV. (2013) Darned in 2013: Inclusion of model organisms and linking with Wikipedia. Nucleic Acids Res, 41:258-261.

Michel AM, Roy Choudhury K, Firth AE, Ingolia NT, Atkins, JF, Baranov PV. (2012) Observation of dually decoded regions of the human genome using ribosome profiling data. Genome Res, 22:2219-2229.

Sharma V, Firth AE, Antonov I, Fayet O, Atkins JF, Borodovsky M, Baranov PV. (2011)A pilot study of bacterial genes with disrupted ORFs reveals a surprising profusion of protein sequence recoding mediated by ribosomal frameshifting and transcriptional realignment. Mol Biol Evol, 28:3195-3211.

Ivanov IP, Firth AE, Michel AM, Atkins JF, Baranov PV. (2011) Identification of evolutionarily conserved non-AUG-initiated N-terminal extensions in human coding sequences. Nucleic Acids Res, 39:4220-4234.

Atkins JF, Baranov PV. (2007) Duality in the genetic code. Nature, 448: 1004-1005.

Full list of LAPTI Publications

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