Clinical OMICS

MAR-APR 2018

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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Page 37 of 51

In the Lab 36 Clinical OMICs March/April 2018 Flu Genome Study May Help Efforts to Detect Potential Pandemics Scientists at Washington University School of Medicine in St. Louis say they have identified features of the influenza virus genome that affect how well the vi- rus multiplies. The team believes its find- ings published in Nature Communications, could help improve surveillance to detect a potential pandemic. The features that were identified are similar, but not identical, across viral strains. It's possible that the extent of sim- ilarity between strains influences whether two flu viruses can mix their genetic mate- rial to make a hybrid virus with the poten- tial to explode into pandemic flu, accord- ing to the scientists. The research team found that parts of the virus's RNA genome fold like origami into specific 3D shapes and that these shapes are necessary for the virus to mul- tiply. When they mutated the genome to change the shapes, the viruses did not reproduce well. "Silent" mutations that left the shapes intact, on the other hand, did not affect multiplication. There are thousands of different flu vi- ruses in the world, each differing slightly in their genetic sequence and, most likely, the shapes into which their RNA folds. Flu viruses whose genomes form very differ- ent 3D structures may not be able to re- combine into a new strain. n a similar dataset in size and genetic anomalies, he said. "We will look at our data in light of these findings. It offers a very compelling analysis." Skuse said he is impressed with the thought that went into the interpre- tations of data, the genetic anomalies and how they were be classified. The 15-question survey used in the study to collect information from parents provided valuable information and could be built upon in the future. In the study, researchers said they used their finding to propose a com- bined classification of phenotypic severity: mild (little impairment of either), moderate (impairment mainly to motor skills), and severe (impair- ment of both IQ and motor skills). "The way [the researchers] pre- sented the relationship between these classes of genetic anomaly and pheno- typic data has not been seen before. It clearly requires further consider- ation," he said. "The study is exem- plar and sets up a template for future studies." (continued from previous page) Catherine Lord, Ph.D., Columbia University nopparit / Getty Images blueringmedia / Getty Images Epigenetic Modulation Helps Restore Myelin to Damaged Nerves In research published in the journal Na- ture Medicine, scientists at Cincinnati Children's Hospital Medical Center, led by Q. Richard Lu, Ph.D., described how they determined that histone deacetylase 3 (HDAC3), an epigenetic enzyme, inhibits the generation of new myelin. They also reported that they inhibited this inhibi- tor in a mouse model of peripheral nerve injury, an intervention that enhanced myelin growth and regeneration and im- proved functional recovery. "HDAC3 antagonizes the myelinogenic neuregulin–PI3K–AKT signaling axis," the authors wrote. "Moreover, genome-wide profiling analyses revealed that HDAC3 represses promyelinating programs through epigenetic silencing while coor- dinating with p300 histone acetyltransfer- ase to activate myelination-inhibitory pro- grams that include the HIPPO signaling effector TEAD4 to inhibit myelin growth." To identify possible therapies, the inter- national team of investigators performed small-molecule epigenetic screening for compounds that inhibit enzymes in- volved in epigenetic changes on chromo- somes. "Remarkably, temporary inhibition of HDAC3 robustly accelerated the forma- tion of myelin that helps insulate periph- eral nerves," Lu said. "This promoted functional re- covery in the animals after peripheral nerve injury." Translating data in the cur- rent study to clinical application in human patients will require extensive additional research, Lu stated. This includes looking specifi- cally at some demyelinating diseases that affect the central nervous system, such as multiple sclerosis. n

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