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Human genetics studies provide insight into how an ideal drug might target and modify a disease-causing protein. But, oftentimes, these “experiments of nature” indicate the need for drugs that act through novel mechanisms. by ӳý researchers Stuart Schreiber, Joanne Kotz, and colleagues published in Cell outlines recently completed, decade-long Molecular Libraries Program (MLP) — an NIH effort to identify small-molecule probes that could help explore human biology. From malaria to multiple sclerosis and diabetes, the authors describe how these probes are enabling the investigation of disease hypotheses that would be difficult to explore via other approaches, advancing therapeutic discovery.

The ӳý is designed for collaboration. Visitors will notice walls of glass that promote transparency, “living rooms” with casual seating for informal meetings, and writable, “whiteboard walls” stocked with dry erase markers for spontaneous brainstorming sessions. Some of these writable walls sport chemical formulas or structures and others detail new hypotheses. In the ӳý’s 320 Charles Street building, however, members of the Genomics Platform have transformed one whiteboard wall into an essential management tool, known as the “Strategy Board."

Although it has been known for some time that cancer genomes can be replete with rearrangements and mutations that accumulate over time, sequencing efforts recently identified additional types of mutations that appear to happen within a single cell cycle. One of these types, chromothripsis, causes rearrangements and DNA copy number variation restricted to only one or a few chromosomes. , ӳý researchers Cheng-Zhong Zhang, Joshua Francis, Matthew Meyerson, David Pellman, and colleagues describe how chromothripsis can occur, involving the formation of “micronuclei,” as an outcome of aberrant cell division. These findings uncover a potentially under-acknowledged source of genetic variation and show how chromosome segregation errors can contribute to cancer.

Of the more than 80 million known genetic variants, few are well understood for their roles in human health and disease. To overcome this gap in knowledge, large consortia studies need to share data across traditional boundaries — a hard task when there are few standards in place to harmonize those data. In a special report in the , ӳý institute member and Clinical Research Sequencing Platform (CRSP) clinical director Heidi Rehm and colleagues describe the NIH-funded ClinGen program, which aims to be an authoritative central resource for defining the clinical relevance of genomic variants for use in precision medicine and research. wrote about the report, which was among a set of papers published by the journal that addressed the promises and .

Taking advantage of the liver’s ability to collect microbes, a team led by Sangeeta Bhatia of the ӳý and MIT, and Jeff Hasty of the University of California, San Diego, designed a synthetic bacterium to accumulate in – and detect – liver metastases, a pressing clinical need. The team used a safe and widely used probiotic E. coli strain to develop an orally administered diagnostic that can noninvasively indicate the presence of liver metastases by producing easily detectable signals in urine. Appearing in , the study demonstrates the potential for programmable probiotics in diagnostic and, potentially, therapeutic cancer applications. Read coverage of the study in and to learn more.