How stress turns hair gray, cancer drugs may be hiding in plain sight, and more.
By Broad Communications
Credit: Erik Jacobs
Welcome to the January 24, 2020 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Gut reaction to metabolomic screening
The role of specific metabolites that influence the growth and physiology of gut bacteria in inflammatory bowel diseases (IBD) remain largely unknown. A team led by Infectious Disease and Microbiome Program’s Nadine Fornelos (previously postdoctoral researcher), associate member Curtis Huttenhower, research scientist Hera Vlamakis, and core institute member Ramnik Xavier, along with colleagues in the Metabolomics Platform, screened a panel of IBD-related microorganisms and metabolites. Reporting in Nature Microbiology, the researchers found that N-acylethanolamines (NAEs), a class of endogenously produced signaling lipids, which are typically elevated in IBD, have the potential to shift gut microbiota toward an IBD-like state. The study suggests NAEs may become a biomarker for IBD, with future therapies targeting NAE metabolism.
Fight or flight turns them white
There’s new evidence to support the old adage that stress gives you gray hairs: a team including associate member Ya-Chieh Hsu, Bing Zhang (Harvard Stem Cell Institute), Regev lab postdoctoral associate Sai Ma, associate member Jason Buenrostro, core member Aviv Regev, and others in the Cell Circuits Program found that stressed mice undergo early hair greying through depletion of melanocyte stem cells (MeSCs). When sympathetic nerves relay “fight or flight” responses, noradrenaline causes sleeping MeSCs to convert into melanocytes and exit their hair follicle niche, leaving no MeSCs behind to make new pigment cells. Described in Nature, the study demonstrates how an organism’s physiological state can influence its somatic stem cells. Read more in Nature News and Views, Time, CNN, and The New York Times.
Challenges of international direct-to-participant research
Direct-to-participant recruitment and enrollment via the internet is an effective way to conduct genomic research, especially on rare diseases. However, institutional review boards and research ethics committees have been reluctant to approve this approach for international research because of concerns about its legality in other countries. Andrea Saltzman, director of human subjects compliance at Broad, and colleagues surveyed expert collaborators on the laws, policies, and guidelines from 31 countries to examine the ramifications of extending the direct-to-participant methodology to worldwide genomic research, using research into rare disorders as an example. Their report appears in The Journal of Law, Medicine & Ethics.
How hemoglobin switching works
Boosting fetal hemoglobin (HbF) in sickle cell disease patients is a therapeutic strategy. During normal human development, a protein called BCL11A represses the HbF gene and regulates the switch from fetal to adult hemoglobin shortly after birth, but the mechanism of how BCL11A expression is regulated is unclear. Postdoctoral fellow Anindita Basak, former postdoctoral fellow Mathias Munschauer, institute director Eric Lander, associate member Vijay Sankaran, and their co-workers show that early in blood development, HbF expression is turned on because of an RNA-binding protein called LIN28B, which directly interacts with ribosomes and BCL11A mRNA to suppress the production of the BCL11A protein. Learn more in Nature Genetics and Boston Children's Hospital's Discoveries blog.
A more complicated history of ancient West African foragers
Associate member David Reich and his colleagues analyzed ancient DNA from four children who were buried in the Shum Laka site in modern-day Cameroon some 8,000 and 3,000 years ago. They used the data to build the first comprehensive model of deep African genetic history and reveal that all four individuals are most closely related to Central African hunter-gatherers, despite being from the hypothesized homeland of Bantu languages. This complicates theories about the beginnings of the Bantu language expansion, which is the primary source of ancestry in central, eastern, and southern Africa. Read more in Nature and coverage in Science and The New York Times.