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This Week in Science: Sep 11, 2015

In this week's Science, researchers from Stanford University report how genomic analysis has opened the door to easier production of the chemotherapy agent etoposide. Used in combination with other agents for the treatment of a wide range of cancers, etoposide is currently synthesized using a chemical precursor called podophyllotoxin, which can only be obtained from the slow-growing Himalayan mayapple plant. To overcome this issue, the researchers examined RNA sequencing data from the plant to identify genes involved in podophyllotoxin production. They then genetically altered tobacco plants to express these genes, identifying the compounds they produced using mass spectrometry. Using this approach, the team uncovered six new pathway enzymes that can be used to produce an etoposide precursor that appears to be more potent as a chemotherapy ingredient than podophyllotoxin.

Also in Science, a multi-institute team presents data suggesting that predicting patient response to a new type of cancer immunotherapy may be more difficult than anticipated. The work focused on a melanoma drug called ipilimumab, a monoclonal antibody that activates a patient's immune system by targeting a protein receptor that downregulates immune responses. In their study, the researchers show that patients whose tumors contain many mutations respond best to therapy since these mutations generate a number of new antigen proteins that help activate the immune system. However, only a small percentage of these so-called neoantigens were found in more than one patient who benefitted from the drug, making them difficult to use as predictors of treatment response.

And in Science Signaling, a group of Harvard Medical School researchers publishes a study demonstrating the combination of the genome-editing tool CRISPR and RNAi to screen for potential cancer drug targets. In the work, they focused on patients with mutations in a family of tumor suppressors known as tuberous sclerosis complex 1 (TSC1) and 2 (TSC2), which often leads to cancer and cancer syndromes. Using CRISPR, the researchers deleted either TSC1 or TSC2 in Drosophila cells to create two stable cell lines. They then ran RNAi screens on the cell lines and identified three enzymes that, when downregulated, stopped the growth of cells missing the genes, but not normal cells. The findings were then confirmed in human cancer cells, confirming the enzymes' clinical relevance. GenomeWeb has more on this study, here.

The Scan

Machine Learning Helps ID Molecular Mechanisms of Pancreatic Islet Beta Cell Subtypes in Type 2 Diabetes

The approach helps overcome limitations of previous studies that had investigated the molecular mechanisms of pancreatic islet beta cells, the authors write in their Nature Genetics paper.

Culture-Based Methods, Shotgun Sequencing Reveal Transmission of Bifidobacterium Strains From Mothers to Infants

In a Nature Communications study, culture-based approaches along with shotgun sequencing give a better picture of the microbial strains transmitted from mothers to infants.

Microbial Communities Can Help Trees Adapt to Changing Climates

Tree seedlings that were inoculated with microbes from dry, warm, or cold sites could better survive drought, heat, and cold stress, according to a study in Science.

A Combination of Genetics and Environment Causes Cleft Lip

In a study published in Nature Communications, researchers investigate what combination of genetic and environmental factors come into play to cause cleft lip/palate.