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This Week in PNAS: Mar 31, 2009

Steve Carr's group has used quantitative proteomics (SILAC) and affinity enrichment to provide "unbiased, robust and comprehensive identification" of the proteins that bind to small-molecule probes and drugs. They say the method is scalable and general and, in this paper, apply it to identify targets of kinase inhibitors and immunophilin binders.

Harvard and Boston University's Timothy Lu and Jim Collins used synthetic biology techniques to engineer bacteriophages to make bacteria more susceptible to attack by antimicrobial drugs. They show that by suppressing the SOS network in E. coli with engineered bacteriophage, this improves the killing action of quinolones by several orders of magnitude in vitro and increases survival of infected mice in vivo. "This work establishes a synthetic biology platform for the rapid translation and integration of identified targets into effective antibiotic adjuvants," they write.

Two studies use systems biology techniques to study cancers. In one, scientists used bisulfite sequencing to measure passenger methylation at two CpG-rich regions in fragments of 12 colorectal cancers, hoping to glean some insight into how cancer cells grow into tumors. Methylation patterns were consistent with flat clonal expansions and multiple long-lived cancer stem cell lineages per cancer gland. In another paper, researchers looked at genome-wide expression and copy number variation information for primary endometrial cancers to detect which might recur. They found that aggressive tumors were associated with in vitro activation of PI3 kinase.

In early online publication, scientists have used microarray analysis to find a group of genes downstream of Wnt/β-catenin that are directly regulated by Notch, whose activation is important in colorectal cancer. They show that Notch is downstream of Wnt in colorectal cancer cells through β-catenin-mediated transcriptional activation of the Notch-ligand Jagged1.

The Scan

Pig Organ Transplants Considered

The Wall Street Journal reports that the US Food and Drug Administration may soon allow clinical trials that involve transplanting pig organs into humans.

'Poo-Bank' Proposal

Harvard Medical School researchers suggest people should bank stool samples when they are young to transplant when they later develop age-related diseases.

Spurred to Develop Again

New Scientist reports that researchers may have uncovered why about 60 percent of in vitro fertilization embryos stop developing.

Science Papers Examine Breast Milk Cell Populations, Cerebral Cortex Cellular Diversity, Micronesia Population History

In Science this week: unique cell populations found within breast milk, 100 transcriptionally distinct cell populations uncovered in the cerebral cortex, and more.