Research Roundup: November 12, 2021

Welcome to the November 12, 2021 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.

Feel the positivity

Bacterial species interact in numerous ways that are broadly considered either negative (one blocks another's growth) or positive (one promotes the other). The latter are considered rare, but in Science Advances, Jared Kehe, core institute member Paul Blainey, Jonathan Friedman (Hebrew University), and colleagues report that such relationships may actually be quite common. Using kChip, a co-culture platform developed in the Blainey lab, they studied 180,000+ interactions between 20 soil bacteria. Their findings suggest that species' positive interactions are generally parasitic (one's growth improves at another's expense) and that strongly-growing bacteria bolster the growth of those that do not typically thrive in culture.

Modeling T cell dynamics before and after immunotherapy

Donor lymphocyte infusion (DLI) is a common immunotherapy for relapsed leukemia. Efficacy varies among patients and the mechanisms, cell types, and pathways underlying tumor sensitivity to therapy are unclear. In Cell Reports, Pavan Bachireddy, Elham Azizi, Dana Pe’er, institute member Catherine Wu of the Cancer Program, and colleagues investigate tumor microenvironments before and after DLI in human bone marrow biopsies, integrating single T cell transcriptomics, chromatin accessibility, and single T cell receptor sequencing data. They found that late- and early-differentiated T cells dominated before and after DLI, respectively, in therapy-responsive tumors, while multiple dysfunctional states were present in resistant tumors. Finally, the team describes Symphony, a computational method for connecting cell types to gene regulatory networks.

How microbiome molecules impact the gut

The endoplasmic reticulum (ER) plays an important role in quality control of cellular proteins. In Genome Biology, a team led by Xiaobo Ke (Novartis) and core institute member Ramnik Xavier, director of the Klarman Cell Observatory and Immunology Program and co-director of the Infectious Disease and Microbiome Program, describes the microbiome-related metabolites in the gut that could influence this organelle's stress response, which may contribute to inflammatory disorders of the gut. The researchers identified both inducers and suppressors of the ER stress response, and demonstrate that these molecules affect the ER via protease inhibition or lipid metabolism interference. The work provides insight into the dynamic pathways the intestinal epithelium uses to monitor microbial metabolites.

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