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RNA emerges from DNA's shadow and wine genomics gets $5m

Tuesday 22nd July 2008
RNA structure. Courtesy:http://www.genomebc.ca/

This month, the RNA, the transporter of genetic information within the cell, has emerged from the shadow of DNA to become one of the hottest research areas of molecular biology, with implications for many diseases as well as understanding of evolution at the Granada conference. Meantime, researchers from Canada, New Zealand and the US are to work on the WineGen R&D programme with the University of British Columbia.

The RNA field is complex, requiring access to the latest equipment and techniques of imaging, gene expression analysis and bioinformatics, as well as cross-pollination between multiple scientific disciplines. This has led to a major European push to bring the field together via a network of overlapping multidisciplinary projects, spearheaded by the European Science Foundation (ESF) with its EUROCORES Programme RNAQuality.

The great potential of the RNA research field to solve a variety of fundamental problems relevant for understanding of life and predicting cures for diseases was unleashed at the RNAQuality Programme's first conference, held in Granada in June 2008. As well as many European groups, the conference was represented by leading pioneers from the US in the field, who welcomed the new initiative as an important collaborative force.

RNA was once considered to be just the faithful messenger taking genetic information from the genome to the ribosome, or protein factory, but that view has been blown away by recent research.

It is now known that RNA has additional roles in regulating gene expression and as an important structural component both in the cell nucleus and in the ribosomes. Furthermore, errors in transcribing RNA from DNA are frequent and require a variety of elaborate quality control mechanisms to prevent both mis-regulation of genes, and manufacture of aberrant RNA and protein fragments that clog up the workings of the cell, and that if unchecked can cause a variety of disorders, including cancers.

Delegates at the conference heard how there is great potential for creating new compounds that manipulate the cell's apparatus for transcribing DNA into RNA to overcome a number of serious disorders caused by deleterious mutations in specific genes, as opposed to problems with the RNA itself.

Jacobson also presented one of the most exciting developments, a molecule that overcomes a common deficiency in genes that prevents their being read right up to the end of their sequence during transcription. Jacobson pointed out that there are about 2400 human genetic disorders resulting from mutations that cause genes to be incompletely read, including cystic fibrosis and muscular dystrophy.

A drug based on the molecule is now entering trials that could lead to it becoming generally available. Results so far indicate dramatic improvements in both cystic fibrosis and muscular dystrophy sufferers, although it is only suitable for those disorders caused by the presence of a premature stop sign in a gene sequence, as a result of a mutation. It does though highlight the huge therapeutic potential of the research into RNA and its quality control.

Significant progress has been made in different aspects of RNA research over the last decade or more, leading to the current situation where many groups are working on different aspects of the problem. The challenge being met by the ESF's RNAQuality Programme is to bring these groups together, and make Europe a much greater force in the field, according to Jim Anderson, from Marquette University's Department of Biological Sciences in the US.

Another important aspect of RNA research lies in the interaction between DNA transcription, and the physical structure both of the membrane-bound cell nucleus and the genome coiled within it. Genes are transcribed within the nucleus and the resulting RNA molecules then emerge through small holes that are connected to the genome by proteins called nuclear pore complexes.

In one of the presentations, Nick Proudfoot from Oxford University in the UK explained how some genes are enhanced by being close to the nuclear pore complex, indicating a close relationship between gene expression and nuclear structure that must have played out through evolutionary history.  Another point to emerge from Proudfoot's presentation was how some genes are expressed more efficiently for a different reason, because the section of DNA containing their sequence is coiled locally into a loop, rather than as a branch.

Quite simply, this speeds up the transcription process of reading the gene because the enzyme concerned, RNA Polymerase, can just keep on encircling the loop. As Proudfoot explained, this is relevant for quality control as well. "They may afford quality control by "telling" the polymerase it is transcribing a bona fide gene, with a proper beginning and end," said Proudfoot. "Otherwise the polymerase may have initiated erroneously." The existence of a DNA ring makes it easier to identify the sequence corresponding to a gene, and transcribe it correctly.

The RNAQuality Programme comes under the ESF's EUROCORES (European Collaborative Research) scheme and will last three years. The aim of the European Collaborative Research (EUROCORES) Scheme is to enable researchers in different European countries to develop collaboration and scientific synergy in areas where European scale and scope are required to reach the critical mass necessary for top class science in a global context.

The scheme provides a flexible framework which allows national basic research funding and performing organisations to join forces to support excellent European research in and across all scientific areas. The European Science Foundation (ESF) provides scientific coordination and support for networking activities of funded scientists currently through the EC FP6 Programme, under contract no. ERAS-CT-2003-980409. Research funding is provided by participating national organisations.

Wine genomics in Canada, New Zealand and the US
Source: http://www.lbl.gov/ By fermenting lactic acid, Oenococcus oeni plays a critical role in de-acidifying wine. Photo courtesy of Jeff Broadbent and Utah State University.

Genome BC is behind the launch a new wine genomics R&D program WineGen and is providing $5m in funding support which involves researchers from Canada, New Zealand, and the US and be led by Drs Hennie van Vuuren and Steve Lund of the University of British Columbia Wine Research Centre and Drs Richard Gardner from the University of Auckland, and Michael Trought of the Marlborough Wine Research Centre in New Zealand.

Other participants include Dr Chris Owens from the US Department of Agriculture, Dr Terrence van Rooyen, Niagara College in Ontario and BC wineries Calona Vineyards and Poplar Grove Winery.

"Genome BC is very pleased to support this new initiative which builds on knowledge gained in a previous Grape Gen project, which was a collaboration with Genome Espana," said Dr Alan Winter, president and CEO of Genome BC. "Wine production in BC has expanded significantly over the last decade and has become one of the province's leading agri-businesses. We look forward to the results the team will bring forward that will contribute to overall innovation of viticulture and enology and the advancement of Canadian wines on the international market."

The three countries represented in the project are growing contributors to global wine production and by combining this global expertise the team expects to identify changes at the molecular and biochemical level that effect three important aspects of wine making: grapevine cultivation, grape processing and fermentation by yeasts.

"The process of producing superior wines is a complex process involving many varying factors such as the inherent characteristics of the grape, the effects of environmental factors on berry ripening and flavour and the nature of yeasts as part of the fermentation process. Therefore, we are looking forward to participating in various aspects of the project and to the development of new biomarkers that will assist all New World wine growing areas," said Jeff Del Nin, winemaker at Burrowing Owl Winery in the South Okanagan.

The project will also include social science research, led by Dr Michael Howlett at Simon Fraser University. The project will evaluate the existing interactions within the Canadian wine industry in the context of adopting and regulating innovative technologies and interactions between industry, science, policy-makers, and the general public.

Sources: http://www.esf.org/rnaquality
 http://www.esf.org/eurocores
http://www.genomebc.ca/

 

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