Research Roundup: June 14, 2019
A community approach to microbial engineering, a step-wise look at blood cell production, a computational view into matrix manufacture, and more.
Welcome to the June 14, 2019 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Screening microbial communities
Microbial communities have potential applications in biotechnology, agriculture, and medicine, but without an accurate way to predict their interactions and environmental responses, current strategies to engineer them are limited. In PNAS, a team led by Jared Kehe, Anthony Kulesa, and core institute member Paul Blainey presents the kChip, a platform to construct and test synthetic communities of microbes at a scale of approximately 100,000 communities per day. As a demonstration, the team identified sets of bacteria that promote the growth of the model plant symbiont Herbaspirillum frisingense. The kChip platform could aid discovery of microbial consortia for purposes such as suppressing pathogens or degrading materials for biofuel production, as well as testing general theories of ecology.
The birth of a blood cell
A multi-step process called erythropoiesis creates red blood cells, and a deeper knowledge of this process could help us better understand anemias and develop new therapies. In this week’s Cell Reports, Leif Ludwig, Caleb Lareau, associate member Vijay Sankaran in the Program in Medical and Population Genetics, core institute member and Klarman Cell Observatory director Aviv Regev, and colleagues chart stage-specific transcriptional states and chromatin accessibility across stages of human erythropoiesis. Their analysis suggests stage-specific transcription factor activities, maps genetic variants underlying diseases and traits to regulatory regions, and identifies TMCC2 as a regulator in terminal erythropoiesis. This work is a helpful resource for further illumination of genetic regulators in red blood cell production and causes of associated diseases.
Distraction deflectors
To survive, humans and animals must extract relevant signals from the environment. Reporting in Neuron, a team led by the McGovern Institute's Miho Nakajima and Stanley Center for Psychiatric Research associate member Michael Halassa discovered that the brain’s prefrontal cortex (PFC) regulates sensory activity of the thalamus through a novel basal ganglia pathway, which helps select between visual and auditory stimuli by suppressing the distracting modality. The new PFC-GC-thalamus pathway enhances sensory discrimination and is used to suppress background noise in a goal-directed way.
A microbial sugar is a bitter pill in IBD
Researchers have long linked changes in the gut microbiome with inflammatory bowel disease, but the biology driving those links has been unclear. This week in PNAS, a team led by Matthew Henke, Chelsi Cassilly, and Broad senior associate member Jon Clardy at Harvard; and Douglas Kenny, Hera Vlamakis, and core institute member and Infectious Disease and Microbiome Program co-director Ramnik Xavier at the Broad revealed that one such gut bug, Ruminococcus gnavus, produces a polysaccharide that irritates the immune system in Crohn's disease. Prior work associated R. gnavus with Crohn's flare-ups; this is the first study to pinpoint a molecular mechanism behind the connection. Read more in a Broad news story.
One can be told what the (extracellular) matrix is
The extracellular matrix (ECM), composed of secreted proteins, is vital for the survival, growth, and migration of many types of cancer. However, little is known about the biochemical pathways involved in ECM secretion. A team led by Haoxin Li and core institute member Stuart Schreiber (both in the Chemical Biology and Therapeutics Science Program) and colleagues used computational approaches to look for genes whose perturbations disrupt ECM secretion. Reporting in Cell Chemical Biology, the team confirmed that 6-phosphogluconate dehydrogenase, a cellular enzyme involved in carbohydrate metabolism, is an essential component required for ECM secretion, thus providing new insight into a specific metabolic pathway.
A new autism model, courtesy of CRISPR
Mouse studies of autism and other neurodevelopmental disorders have yielded drug candidates that have been tested in clinical trials; however, none have succeeded. A US/China research team led in part by institute member Guoping Feng in the Stanley Center has used CRISPR genome editing to engineer macaque monkeys to express an autism-linked mutation in a gene called SHANK3. Writing in Nature, they report that the engineered macaques display behavioral and neurological patterns similar to humans with autism spectrum disorder. The new model, they say, could help scientists to develop better treatment options for some neurodevelopmental disorders. Learn more in an MIT news story and coverage in Spectrum.
To learn more about research conducted at the Broad, visit broadinstitute.org/publications, and keep an eye on broadinstitute.org/news.
