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Welcome to the October 25, 2019 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the ӳ����ý and their collaborators.

Prime editing debuts

In , a team led by postdoctoral fellow Andrew Anzalone and core institute member David Liu, who is also director of the Merkin Institute of Transformative Technologies, describes a new CRISPR genome editing system called "prime editing” that has the ability to directly make targeted insertions, deletions, and all possible single-letter changes in the DNA of human cells. The system combines two of the most important proteins in molecular biology — CRISPR-Cas9 and a reverse transcriptase — and a new type of engineered guide RNA into a single machine with the potential to correct up to 89 percent of known disease-causing genetic variations. Learn more in a ӳ����ý news story and infographic, and check out coverage in , , and .

TB or not TB

Senior group leader Michael Gillette, institute scientist and Proteomics Platform senior director Steven Carr, ӳ����ý alum Rushdy Ahmad, and their colleagues have developed a blood-based test that can accurately distinguish patients at increased risk for active tuberculosis (TB) from those likely to have other lung problems in geographically diverse regions, including Africa, Asia, and South America. The new test, described in a paper in , is a five-protein panel and approaches the performance criteria established by the World Health Organization for TB triage tests. The study is also a critical step toward a simple, low-cost blood test that can be used anywhere, including low-income areas, for triaging patients suspected of having active TB. Read more in a ӳ����ý news story and from the and .

PaTCHing up the noise filter

In noisy environments, some people with autism are unable to tune out distracting sensory information. Reporting in , Miho Nakajima (McGovern), L. Ian Schmitt (McGovern), institute member Guoping Feng, and associate member Michael Halassa of the Stanley Center for Psychiatric Research showed that mice missing the PTCHD1 gene, which is altered in one percent of people with autism, have deficits in two brain circuits: one that filters noise, and another that helps the brain switch attention between sensory inputs. Targeting both circuits pharmacologically restored the animals’ ability to extract signals in noisy environments. The work, featured in , illustrates the importance of mapping and targeting multiple circuits in neurological disorders.

Maps predict cancer therapy’s chances

One of the greatest challenges in cancer treatment is the ability of tumors to mutate and develop resistance to cancer therapy. Even though combining two therapies can be a potential treatment option, in most cases it is hard to test in clinical trials. ӳ����ý alum Cory Johannessen (now at Novartis), Dan Landau (Weill Cornell), senior group leader of the Genetic Perturbation Platform Federica Piccioni, and collaborators developed a new suite of experimental and computational techniques that allow scientists to generate genotype-fitness maps of tumor cells. These maps may help predict how tumors will develop resistance to a particular drug or combination of drugs, informing improved treatment strategies. Read more in and a news story from .

Multitasking like a cellular boss

Our lymph nodes contain many types of cells beyond immune cells that play regulatory roles — sometimes more than one — that scientists are only beginning to appreciate. Case in point: Fibroblastic reticular cells (FRCs) are known to keep activated T cells in check by curtailing their growth and proliferation. But in , institute member Arlene Sharpe, associate member Nicholas Haining of the Cancer Program, and colleagues report that FRCs also help shape newly activated T cells' fate and function, providing signals (such as IL-6) that help the T cells live longer and support their later conversion from effector into memory cells.

To learn more about research conducted at the ӳ����ý, visit broadinstitute.org/publications, and keep an eye on broadinstitute.org/news.