Monday | 24 November, 2008
Australian Biotechnology News
Sequencing most fowl: a poultry challenge
Deciphering vertebrate development, sorting out the roosters from the hens and taking on bird flu – dare we say, all in one fowl swoop – that is the job of CSIRO’s Dr Mark Tizard, who has created a new microRNA catalogue for the humble chook.
Fiona Wylie 13/06/2008 15:34:00

Mark Tizard and colleagues have recently had a paper accepted for publication in Genome Research that catalogues a substantial list of microRNA (miRNA) sequences from the chicken. Not so exciting you may think, but it actually provides a valuable new resource for researchers working with chickens either as a model system for vertebrate development or as a production species.

Assembling the catalogue also ticks off the first box in an ambitious project being led by Tizard, a senior scientist based at the Australian Animal Health Laboratory (AAHL) in Geelong, Victoria, to characterise the roles of miRNAs in chicken development and physiology. The project is a joint effort between CSIRO Livestock Industries, Plant Industry and Entomology as part of a CSIRO 'Emerging Science' initiative called Cellular Reprogramming.

miRNAs are single-stranded RNA molecules of about 18-24 nucleotides in length that are important in regulating gene expression. It is now known that these molecules use RNA interference pathways. Tizard's miRNA project grew out of research on applying RNAi technologies in livestock therapeutics, led by fellow CSIRO researcher Dr Tim Doran (see ALS May/June 2007). Specifically, the group is using RNA interference to target avian influenza.

By way of background to his own research, Tizard recalled how excited Tim Doran was when the first lot of work describing the RNAi mechanism started appearing several years ago, including the groundbreaking, Nobel Prize-winning papers by Fire and Mello.

At the same time, similar observation were being made in plants closer to home by Dr Peter Waterhouse and Dr Ming-Bo Wang at CSIRO Plant Industry in Canberra, who developed patented DNA-delivered (dd)RNAi technology based on their observations of RNAi in plants.

Doran immediately saw the potential of this previously unrecognised level of gene regulation via blocking mRNA translation, and was keen for CSIRO Livestock Industries to join in. The applications were immediately apparent, including trait modification and disease prevention. "It was around that same time that microRNAs were being uncovered," Tizard says. "DNA sequences that affected the timing of morphology changes were identified in C. elegans. These turned out to be tiny fragments of RNA nowhere near big enough for a coding sequence ... miRNAs.

"Now, CSIRO Livestock Industries has invested a lot of money over the years in trying to understand animal genetics and how the genetics is delivered. Here was evidence of a whole new layer of control in the cell for gene expression, and with that, effects on animal growth and development. So, with Tim's RNAi project up and running four or five years ago, it became obvious that we should be also looking at miRNAs in our systems. I was lucky enough to be in the right place and the right time to start this project."

The team chose the chicken as the model system for the miRNA project for several reasons. Firstly, the group at Geelong had a lot of experience with the chicken as a model organism and therefore many of the tools were already in place.

Secondly, the chicken is a fundamental model for studies of vertebrate development, which has importance for CSIRO interests and the wider research community. In particular, they are trying to better understand development of the immune response in the chicken production environment and how to enhance that immunity so that the animals remain healthier during production and more resistant to pathogenic attack, which usually viral.

This particular focus of course relates to the broader CSIRO project on avian influenza. And finally, from more of a pragmatic viewpoint, scientists can work on chicken embryos without having to go near the living animal.

"Chickens pump out these lovely sterile packages that act as a critical resource for our experiments," Tizard says. "This means we can study embryo development with precision at early stages without going near the mother.

"This is a major consideration in terms of the animal welfare and animal ethics requirements for research in this day and age. We are not impacting on the grown bird at all."

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