Designing a better pancreatic cancer drug, single-cell methods head-to-head, and a new consortium probes COVID-19 outcomes
Research Roundup: April 10, 2020
Welcome to the April 10, 2020 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
On the double
Doublecortin like kinase 1 (DCLK1) is involved in several human cancers, particularly pancreatic ductal adenocarcinoma (PDAC), but the kinase has not been studied thoroughly. A team led by associate member Nathanael Gray in Aviv Regev’s lab, Fleur Ferguson (Dana-Farber), and Behnam Nabet, a postdoctoral scholar in Bill Hahn’s group, used chemoproteomic profiling and structure-based design to develop a potent, selective inhibitor of DCLK1, known as DCLK1-IN-1. Described in Nature Chemical Biology, the molecule inhibited DCLK1 in patient-derived PDAC organoids, with cell motility-related changes in the organoids’ transcriptomes and proteomes. The study’s assays, tools, and datasets could be used to help reveal DCLK1 function and its role in tumor biology.
Benchmarking single-cell RNA sequencing
Single-cell RNA sequencing (scRNA-seq) methods have helped advance major scientific discoveries and large-scale mapping projects. However, these methods have not been extensively benchmarked. Two groups, one led by Broad researchers and the other led by CNAG-CRG (Barcelona, Spain) researchers and their collaborators, took complementary approaches to provide comprehensive comparisons of benchmarking methods. Reporting in Nature Biotechnology, postdoctoral associate Jiarui Ding, research scientist Xian Adiconis, computational scientist Sean Simmons, senior group leader and research scientist Joshua Levin from the Stanley Center for Psychiatric Research and the Klarman Cell Observatory, and colleagues developed scumi, a computational analysis tool to directly compare scRNA-seq methods. Both studies provide guidance to researchers on choosing among available scRNA-seq methods. Read more in this Nature Bioengineering blog and the accompanying CNAG-led paper in Nature Biotechnology.
Looking to our genes to understand COVID-19 outcomes
The rapidly growing COVID-19 Host Genetics Initiative is fostering collaboration around the globe to understand whether genetics can help explain why some COVID-19 patients fare better than others. Institute member Mark Daly, co-director of the Program in Medical and Population Genetics and director of the Institute for Molecular Medicine, Finland (FIMM), spoke to the Broadminded Blog about how the initiative came together and what its members hope to achieve. See additional coverage about the initiative in the Wall Street Journal (paywall).