This week, PNAS reports on a new method to study small molecule metabolites in C. elegans, especially how they might interact synergistically. Using a NMR-spectroscopic method, differential analysis by 2D NMR spectroscopy (DANS), they were able to compare wild-type C. elegans and a mutant lacking pheromone signaling genes to identify both known and unknown ascarosides – in variable concentrations, these molecules can be both sex pheromones and developmental regulators. A commentary puts the work in the context of drug discovery, and how ferreting out drug compounds could be improved if it's done knowing that these molecules interact with other compounds in vivo as well as have active analogs.
In early online publication, work led by first author John Landers at University of Massachusetts Medical School used a genome-wide association study to find a SNP within the kinesin-associated protein 3 (KIFAP3) gene that is associated with increased survival in sporadic amyotrophic lateral sclerosis. In fact, homozygosity conferred a 14-month survival advantage, they say. Further analysis showed that decreased KIFAP3 expression was correlated with increased survival.
University of Florida's Grant McFadden is the senior author on a paper that also appeared in the early online edition of PNAS looking at interactions between viral and host proteins. Using a yeast two-hybrid screen against a variety of human cDNA libraries, they performed the "first systematic protein interaction screening of the unique variola virus proteome." They found several interactions, notably between variola G1R, an ankryin/F-box containing protein, and human nuclear factor kappa-B1 (NF-κB1)/p105. "This represents the first direct interaction between a pathogen-encoded protein and NF-κB1/p105," they write, suggesting a role in controlling the innate immune response.
Rudolf Jaenisch is senior author on collaborative work that used a small molecule — instead of a transcription factor gene — to reprogram murine fibroblasts to iPS cells. "Small molecules offer an alternative to replace virally transduced transcription factors with chemical signaling cues responsible for reprogramming," they write. Using a small-molecule screening platform to identify compounds that could replace the reprogramming factor Klf4, they found one, kenpaullone, that could activate Nanog expression without the reprogramming factor.