Molecular 'zip-code' research receives major fundin

A University of Otago scientist is part of an international collaborative team granted more than US$1m to study the hidden mechanisms behind ensuring that components of cells are properly organised.

The Human Frontier Science Program, based in Strasbourg, France, awarded the grant to Otago Biochemistry Senior Lecturer Dr Chris Brown and colleagues at universities in the United States and Switzerland. The project is led by Dr Ian Macara of the University of Virginia, USA and the third group is led by Professor Anne Spang of the University of Basel in Switzerland.

The project's title is "In search of conserved mRNA localization and anchoring mechanisms".

Dr Brown says that, as living cells need to be highly organised, many of their components are transported to particular places and anchored there.

"Disruptions in this transport and localisation cause disease, particularly neurological ones," he says.

The three research teams will work together to investigate hidden molecular "zip codes" that specify the destinations for the transport of molecules known as messenger RNA (mRNA). mRNAs are transcribed with the information from DNA that provides instructions for making proteins.

Once created, proteins are transported to their correct location in the cell or, more efficiently, made at that location from mRNAs that have been moved there, he says.

"Although the mechanisms that move proteins to their destinations have been intensively investigated, those that carry mRNAs have been much less studied. Indeed, RNAs have only recently been shown to have a growing number of new roles and unexpected qualities in cells."

Dr Brown says the zip codes have only been deciphered for a few RNAs.

"An important goal of this project is to create intelligent methods that can find these codes. We will look at unanswered fundamental biological questions such as are many, or just a few, key RNAs localised?"

Other lines of enquiry include how many different zip codes exist, and have they been conserved through evolution.

Dr Brown is an expert in computational analysis of RNA sequences who has developed and integrated new tools to analyse complex mRNA elements on a genomic scale.

For the project, he will develop new computer programmes for zip code identification, using existing data sets of mammalian and yeast mRNAs. These methods will be refined by testing their predictions through experiments carried out by his collaborators.

The analysis of large amounts of genomic sequence data at Otago in this international bioinformatics project is enabled by the KAREN network. KAREN is New Zealand's ultra-high speed research and education network, which is capable of transferring data at up to 10,000 times the speed of a standard broadband connection.

"We will also investigate the evolutionary conservation of the zip codes from yeast to man. By combining the diverse expertise of a cell biologist, a yeast geneticist, and a bioinformatician, we are in a unique position to uncover fundamental principles of mRNA localisation."

Dr Brown says the researchers' ultimate goal is to unravel a fundamental dictionary of RNA zip codes.