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With EC Cash, European Consortium Starts Four-Year siRNA, miRNA Research Project

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The European Commission has awarded a consortium of RNAi and microRNA researchers €11.8 million ($16 million) to support the group’s collaborative effort to gain insights into RNA silencing, its impact on the biology of multiple species, and how it can be applied to human health.
 
“Although there has been rapid recent progress in understanding RNA silencing, there is still much to be done,” David Baulcombe, a researcher at the John Innes Centre’s Sainsbury Laboratory and coordinator of the consortium, called SIROCCO, said in a statement.
 
SIROCCO, short for Silencing RNAs: Organizers and Coordinators of Complexity in Eukaryotic Organisms, aims to “characterize the full complement” of miRNAs and siRNAs in animals and plants. The researchers will use bioinformatics, genomics, biochemistry, cell biology, and genetics to “reveal how these RNAs are produced and processed, how they are transported, and how they target specific genes and RNAs for silencing,” according to the organization.
Additionally, consortium members will investigate the roles that miRNA and siRNA play in how diseases develop and differ, and how small RNAs help to regulate networks and interact with other cellular control mechanisms.
 
SIROCCO expects that its members will develop databases of siRNA and miRNA sequences and functions in multiple organisms, new technologies for detecting and manipulating the RNAs, and techniques by which siRNA and miRNA profiles can be used as molecular markers and in diagnostics.
 
The consortium also expects to identify potential drug targets and methods to boost the specificity of silencing RNAs for therapeutic applications. It “eventually” plans to make public these technologies and information.
 
SIROCCO “tries to cover everything, right from the big database of sequences of silencing RNAs and microRNAs all the way up to trying to look at therapeutic uses for them,” SIROCCO project manager Aileen Hogan told RNAi News this week. This effort includes “new ways of detection, manipulation, cloning, and profiling — things like that.”
 
Although much attention has been placed on the potential of RNAi and miRNAs in human health, the interests of consortium members are wide, Hogan noted.
 
“There are [members] that work on plants, there are [those] who work in mouse systems, and [ones who work in] C. elegans — pretty much all the major model systems at the moment,” Hogan said. “It’s about a third plants, a third vertebrates, and a third non-vertebrates.”
 
Four Objectives
 
SIROCCO has four strategic objectives: The first is to evaluate silencing RNAs as indicators of regulatory states in cells. This includes creating complete catalogues of silencing RNAs in healthy and diseased plant and animal cells and refining methods of detecting these RNAs.
 
The second objective is to examine how siRNA and miRNA machinery integrates into regulatory networks. This goal will require researchers to characterize proteins and subcellular compartments required for siRNA and miRNA processing and activity, and to dissect the regulatory networks of these RNAs.
 
The third aim is to develop techniques for mimicking silencing RNAs by developing rules for siRNA and miRNA specificity and efficacy, as well as improving delivery methods for the RNAs.
 
The final objective is to coordinate, integrate, and disseminate RNAi and miRNA research among consortium members, and ultimately transfer technology developed by the consortium into the hands of industrial partners.
 
Consortium members met for the first time this week in Norwich, UK, to discuss their research projects and how they may be coordinated. They were also assigned to tackle one or more research projects under the program (see accompanying chart below).
 

“Although there has been rapid recent progress in understanding RNA silencing, there is still much to be done.”

However, SIROCCO expects to address other research areas by bringing in additional members through a competitive call slated for later this year, Hogan said.
 
Expected to be part of that call is a search for a new consortium member with expertise in the miRNA field as a replacement for Rosetta Genomics. According to SIROCCO, Rosetta Genomics was supposed to join the alliance but ultimately withdrew “for reasons related to contract administration.”
 
Rosetta officials were not available for comment.
As a result, SIROCCO will announce that it is looking for a new consortium member that can analyze sequences of silencing RNAs in animals, profile human cancer miRNAs, and establish the genetic variability of miRNAs.
 
The consortium will pick the new member with help from “two independent experts,” SIROCCO said.
 
SIROCCO also expects to expand its circle of collaborators by opening up future meetings to interested parties, including ones from industry. The next meeting is scheduled for October, although a venue has not been chosen, Hogan said.
 
SIROCCO was organized as an integrated project under the EC’s Sixth Framework Program and was approved earlier this year, according to Hogan.
 
“The plan of these so-called integrated frameworks … is to try [to] add extra value to the research by taking several expert groups, getting them to work together, and synergize their efforts so that [the whole] is greater than the sum of its parts,” Hogan told RNAi News this week.
 
“The European Commission is very keen on … [getting] added value, so it’s more than just giving people a lump sum of money to use in their lab to pursue their experiments,” she added. The goal is “to think of ourselves as a group and get synergy … so that we can help each other, [as well as] the broader research community by making [information and technologies] publicly available eventually.”

 
 
SIROCCO Partners, Group Leaders, and Key Subprojects
Member Leader(s) Key Subprojects
The Sainsbury
Laboratory
-
Norwich, UK

David Baulcombe

  • Sequence and expression pattern analysis of silencing RNAs in plants
  • Mechanism of RNAi and role of silencing RNAs in transcriptional and post-transcriptional gene silencing
  • mRNA components of silencing RNA-harboring AGO complexes in different systems
  • Specificity of silencing RNA machinery targeting DNA and chromatin in plants
University of Dundee -
Scotland, UK

Gyorgy Hutvagner

Simon Arthur

  • Multiple mechanisms of miRNA function
  • Silencing RNA functions in key developmental processes and diseases
University of East Anglia -
Norwich, UK

Tamas Dalmay

  • Sequence and expression pattern analysis of silencing RNAs in plants
  • Sequence analysis of silencing RNAs in animals
  • Silencing RNA functions in key developmental processes and diseases
John Innes Centre -
Norwich, UK

Caroline Dean

  • Silencing RNA functions in key developmental processes and diseases
University of Cambridge -
Cambridge, UK

Eric Alexander Miska

  • Sequence and expression pattern analysis of silencing RNAs in plants
  • Investigation of silencing RNA expression patterns in animals
  • Mechanism of RNAi and role of silencing RNAs in transcriptional and post-transcriptional gene silencing
Centre National
de la Recherche Scientifique
-
Paris, France

Annick Harel-Bellan

Olivier Voinnet

     
  • Identification of the cis and trans-acting factors regulating miRNA transcription
  • Multiple mechanisms of miRNA function
  • Mechanism of RNAi and role of silencing RNAs in transcriptional and post-transcriptional gene silencing
  • Silencing RNAs in viral infections
  • Silencing RNA functions in key developmental processes and diseases
Max Planck Institutes -
Germany

Detlef Weigel

Elisa Izaurralde

Thomas Meyer

Gunter Meister

  • Sequence analysis of silencing RNAs in animals
  • Multiple mechanisms of miRNA function
  • Mechanism of RNAi and role of silencing RNAs in transcriptional and post-transcriptional gene silencing
  • Determinants of specificity differences of plant and animal silencing RNA machineries
  • Specificity of silencing RNA machinery targeting DNA and chromatin in plants
  • Determinants of efficacy of shRNAs and artificial miRNAs
  • miRNAs in bacterial infections
  • Mechanisms of RNAi suppression by viral proteins
  • Silencing RNA functions in key developmental processes and diseases
European Molecular Biology Laboratory -
Heidelberg, Germany

Stephen Cohen

  • mRNA components of silencing RNA-harboring AGO complexes in different systems
  • Determinants of specificity differences of plant and animal silencing RNA machineries
  • Specificity of silencing RNA machinery targeting DNA and chromatin in plants
  • Silencing RNA functions in key developmental processes and diseases
AlPlanta-Institute for Plant Research -
Neustadt, Germany

Michael Wassenegger

  • Mechanism of RNAi and role of silencing RNAs in transcriptional and post-transcriptional gene silencing
Universita di Roma,
La Sapienza
-
Rome, Italy

Irene Bozzoni

Giuseppe Macino

  • Sequence analysis of silencing RNAs in animals
  • Investigation of silencing RNA expression patterns in animals
  • Identification of the cis and trans-acting factors regulating miRNA transcription
  • miRNA Factory
  • Multiple mechanisms of miRNA function
  • Silencing RNA functions in key developmental processes and diseases
Biotecnologie
Avanzate
-
Naples, Italy
Roberto Di Lauro
  • Sequence analysis of silencing RNAs in animals
  • Investigation of silencing RNA expression patterns in animals
  • Identification of the cis and trans-acting factors regulating miRNA transcription
  • Silencing RNA functions in key developmental processes and diseases
Exiqon -
Vedbaek, Denmark
Peter Mouritzen
  • Sequence and expression pattern analysis of silencing RNAs in plants
  • Investigation of silencing RNA expression patterns in animals
  • Identification of the cis and trans-acting factors regulating miRNA transcription
  • Determinants of efficacy of shRNAs and artificial miRNAs
  • Genome-wide analysis of miRNA function
University of Aarhus -
Aarhus, Denmark
Jorgen Kjems
  • Investigation of silencing RNA expression patterns in animals
  • Identification of the cis and trans-acting factors regulating miRNA transcription
  • miRNA Factory
  • Processing of miRNA precursors by Drosha/Pasha and Dicer
Friedrich Miescher Institute for Biomedical Research (part of the Novartis Research Foundation) -
Basel, Switzerland
Witold Filipowicz
  • Processing of miRNA precursors by Drosha/Pasha and Dicer
  • Multiple mechanisms of miRNA function
Hubrecht Laboratory (a research institute of the Royal Dutch Academy of Sciences) -
Utrecht, The Netherlands
Rene Ketting
  • Sequence analysis of silencing RNAs in animals
  • Multiple mechanisms of miRNA function
  • Genome-wide analysis of miRNA function
Centre de Regulacio Genomica -
Barcelona, Spain
Xavier Estivill
  • Investigation of silencing RNA expression patterns in animals
  • Silencing RNA functions in key developmental processes and diseases
Agricultural Biotechnology Center -
Godollo, Hungary
Jozsef Burgyan
  • Sequence and expression pattern analysis of silencing RNAs in plants
  • Identification of the cis and trans-acting factors regulating miRNA transcription
  • Silencing RNAs in viral infections
  • Mechanisms of RNAi suppression by viral proteins