Welcome to the October 11, 2019 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Roadmap for better IBD drugs
In a Broad Q&A, Daniel Graham and core institute member Ramnik Xavier of the Infectious Disease and Microbiome Program (IDMP) spoke about why it’s been challenging to develop more effective therapies for inflammatory bowel disease (IBD), and what the IBD field needs to do to better understand the disease and, ultimately, benefit more patients. Learn more in a review paper they and colleagues recently published in Cell.
CRISPR Cas13 virus destroyer
You may know the Cas13 enzyme for its RNA-editing and diagnostic capabilities. Now, this CRISPR enzyme can do even more: detect and destroy RNA viruses in human cells in a programmable way. Catherine Freije, Cameron Myhrvold, institute member Pardis Sabeti — all in the IDMP — and colleagues combined Cas13’s antiviral activity with its diagnostic utility to create a single system that may one day be used to both diagnose and treat a viral infection, including infections caused by new and emerging viruses. They call it the CARVER system, which the team revealed this week in Molecular Cell. Learn more in a Broad story.
Napping neurons not needed
Associate member Edward Boyden and his team at the McGovern Institute for Brain Research at MIT have developed a technique, called SomArchon, that allows researchers to monitor the activity of neural circuits in the brains of awake mice and link that activity with specific behaviors. The team engineered fluorescent voltage sensors that are introduced into the brain and then imaged using a conventional light microscope. They showed that they could measure the electrical activity of around 13 neurons at once, in multiple brain regions; previous methods could only capture four cells at most and required more specialized microscopes. Read more in Nature and from the McGovern Institute.
The genetics of PTSD
Researchers and doctors don't know why some people develop post-traumatic stress disorder (PTSD) after experiencing trauma, but suspect genetics is somehow involved. Writing in Nature Communications, Caroline Nievergelt (UCSD), associate member Karestan Koenen in the Stanley Center for Psychatric Research and the Harvard T.H. Chan School of Public Health, and members of the Psychiatric Genomics Consortium's PTSD working group report that PTSD has as strong a genetic component as other psychiatric disorders, with a heritability between five and 20 percent. They came to this conclusion after running the largest and most diverse genome-wide association study of PTSD to date, including more than 30,000 people with PTSD and 170,000 people without. Learn more in a Broad news story.
A new chapter for Raptor
The mTORC1 protein kinase helps the cell respond quickly to changes in nutrient levels by discriminating between nucleotide binding states of Rag GTPases. To explore how mTORC1 tells the different states apart, a team led by Kacper Rogala and associate member David Sabatini at the Whitehead Institute used cryoelectron microscopy to reveal the structure of mTORC1's Raptor subunit bound to a complex incorporating two of the GTPases, RagA and RagC. In Science, they describe how Raptor directly detects RagA's binding state, while its “claw” threads between the GTPase domains to detect that of RagC. The work reveals relationships between Rag state and conformation, and provides a model of active mTORC1 when it is docked on the lysosome.
Gaining “atlas view” insights about disease and health
Reporting in Nature, an international team of researchers involved with the Human Cell Atlas (HCA) consortium has created the human developmental liver cell atlas, a project that provides crucial insights into how the blood and immune systems develop in the fetus. In a second Nature paper, a group of researchers affiliated with the HCA report three newly discovered sub-types of cells that accelerate the scarring process in diseased livers. Finally, also described in Nature, the Human BioMolecular Atlas Program (HuBMAP), an NIH sponsored program, will help HCA efforts to map the human body at single-cell resolution.