ALS Genes and Models: Keys to the CauseA Gene that Compounds the Trouble. Aaron Gitler (left) and Michael Granato (U. Penn.) use simple yeast cells to study how two disease proteins – called TDP-43 and FUS – kill cells. (The proteins are the products of two “hot” ALS genes now under intense study).
Gitler and Granato have made yeasts into a model system that lets them pinpoint the proteins’ toxic regions. Knowing that, in turn, has enabled the researchers to screen for genes whose action might protect the yeasts—and, ultimately, human cells— from the toxic effects. The other side of the coin is that a mutation in one of the genes they uncovered, they believe, may have a role in human susceptibility to ALS. A New Model – A New Gene
Zebrafish pioneer Wim Robberecht (Flanders Inst. of Biotech, Leuven, Belgium) has used his model animals to discover a suspected “accessory” gene, one that might intensify the effect of the two newest confirmed ALS genes. His work suggests a potential target for therapy. From TDP to a Disease Theory
J. Paul Taylor (St. Jude Children’s Research Hospital, Memphis) has created a new fruit fly model bearing the TDP-43 gene—one that has begun to shed light on the gene’s role in motor neuron death in both familial and sporadic ALS. TDP-43’s action very likely influences the behavior of other less-explored genes, and by identifying them and showing how they tie into TDP-43’s biology—this is important, seminal work—Taylor is headed toward finding a significant, overall mechanism of ALS. | 
