Prémio Nobel da Medicina: Andrew Fire e Craig Mello

Nobel da Medicina atribuído a dois norte-americanos: Andrew Z. Fire (esquerda) e Craig C. Mello. Desenvolveram os seus trabalhos na área da informação genética com investigação pioneira no domínio micro-celular e nos chamados interferentes RNA que transportam informação importante entre o ADN e o organismo. Ou seja, estes dois senhores desenvolveram uma ferramenta poderosa de estudar a génese dos embriões que envolve um método genético chamado RNA - ou simplesmente interferência RNAi. E é este RNAi que tem um verdadeiro impacto na pesquisa dos organismos de forma a combater os maus genes. A investigação genética desse mecanismo interferente foi agora premiado, o qual permitirá aprender a transplantar esse método para estudar essas interferências noutros organismos.

Andrew Fire earned his membership in the National Academy of Sciences as a result of the discovery of a highly effective defense mechanism against foreign DNA. Fire brought his lab to Stanford in 2003 from the Carnegie Institution of Washington, along with a supply of nearly see-though 1-millimeter worms called Caenorhabditis elegans. It was in these worms that Fire and his colleagues uncovered molecules that trigger a mechanism called RNA interference, or RNAi, which is now used routinely for understanding what role a gene plays in a cell. In RNAi, short RNA molecules prevent protein from being made from a given gene. This mechanism can eliminate that gene's function and help geneticists understand what role that gene normally plays in the cell. The mechanism is also being tested as part of gene therapy approaches for treating disease.

Fire and his colleague Craig Mello at the University of Massachusetts published a Nature paper in 1998 describing the mechanism of RNAi. Since that time, RNAi has been found to work in a wide range of animal cells, including human cells. In his current work, Fire is piecing together the cellular steps involved in RNAi and related genetic control mechanisms.

Craig C. Mello

Craig Mello, Ph.D. Academic Role: Professor Faculty Appointment(s) In: Program in Molecular Medicine Other Affiliation(s): Center for AIDS Research Interdisciplinary Graduate Program Cell Biology Cancer Center Program in Cell Dynamics

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• Reverse Genetics and RNA Interference During our developmental studies, we became intrigued by some strange properties of the reverse genetic method we were using. This method was analogous to “antisense", wherein the microinjection of RNA complementary to the messenger RNA is used to block the activity of specific genes. However, although antisense methodology generally causes a partial block of gene activity, we observed a remarkably robust interference effect that could spread from tissue to tissue in the animal. In most experiments, nearly 100 percent of the progeny of an injected animal showed phenotypic effects consistent with blocking the targeted gene's activity. Even more surprising, interference could be transmitted for multiple generations in the germline as an extrachromosomal element.