HUGO: Of models and humans

The key to making progress in genomics in the post human genome era is not a blind whole genome approach, an international meet focusing on the power of model organisms and genomic approaches to understanding human diseases felt.

'Genomics, model organisms and diseases', a meeting part of the 13th Human Genome Organisation conference held in India, at Bangalore's National Centre for Biological Sciences had experts believe that faster and more successful progress can be made by targeted functional genomics using either RNAi screens, a powerful technology for functional characterization of biological pathways, or sensitized genetic backgrounds used for traditional microarrays, RNAi and drug screens.

Such approaches, according to the experts, reveal the biology behind diseases that help in developing early biomarkers and potential therapeutic targets. The meet saw researchers from across the world discuss identified pathways in human cell models. It highlighted the use and validity of using model organisms in identifying therapies and understanding diseases. According to the organisers, it was a counter-point to the 'human genome fest in India' that sought to emphasize the value, power and impact such research has and will continue to have on human disease.

Highlighting the effectiveness of selective RNAi screens in culture cells from model organisms, Ramanuj Dasgupta of New York University, USA, said drugs and pathways identified in such screens were efficacious. "These pathways are nearly identical in mammalian cancer models," he pointed out. A number of presentations dealt with the variability in screens and how this can be minimized and analyzed effectively when assaying for molecules involved in specific cell biological events.

Kimberley Caldwell from the University of Alabama, USA said using the roundworm C. elegans model helped identify an existing FDA approved drug that worked in both the worm as well as mammalian cells. The meet discussed the use of C. elegans as a model to study ciliary diseases such as Bardet-Biedl and Mekel's syndrome.

Another session was devoted to the use of fruitfly Drosophila as a model to identify ancient evolutionarily pathways to fight infection. Julien Royet from IDBML, France reported multiple receptors in this model organism and how these receptors help in killing the infecting organism. Some of these findings have implications for human autoimmune disease such as Crohn's. Amita Sehgal from the University of Pennsylvania, USA reported her group's work in identifying a novel Drosophila gene that has roles in homeostatic sleep regulation. "The findings are critical in understanding sleep disorders such as Morvan's syndrome as well modern lifestyles with significant sleep deprivation," she added.

Juan Botas from the Baylor College of Medicine, USA answered a serious question facing researchers when he described how to optimise on different sets of experimental results obtained from a variety of model organisms. "One should look at the commonalities and even perhaps commonalities between all disease models and think in terms of pathways that maybe amenable to therapy," he said. Botas, who has most carefully studied the use of sensitized backgrounds, contended that there was no need to throw out all the data but to think how to decipher more in terms of pathways and the specifics.

Besides the fruitfly, another model organism that hogged the limelight was zebrafish. Its use in the development of the blood-brain barrier was reported as significant for the human brain disorder hydrocephalous. Steve Ekker from the Mayo Clinic, Rochester, USA discussed the enormous burden of nicotine addition in humans. His group has used zebrafish to identify genes that help avoid nicotine responses. Ekker also raised an issue of concern for all model organism researchers – that of the public access of FDA approved drugs soon after testing and validation in model systems and human cells. When can such therapies be swiftly passed on to patients was among other practical questions debated at the forum that highlighted the dilemma among model organism researchers who have to deal with demanding patient fora willing to try risky therapies.

The genomics experts also discussed the ability to successfully use model organisms to identify common 'therapeutic avenues' for multiple neurodegenerative diseases. Guy Caldwell of the University of Alabama, USA talked of an enhancer RNAi screen in a C. elegans Parkinson's model. Huntington models in C. elegans and Drosophila were also extensively discussed.