A breakthrough in in vivo genomic screening, tick checks for science, scaled-down cancer proteogenomics scales up, and more.
Research Roundup: January 31, 2020
Welcome to the January 31, 2020 installment of Research Roundup, a recurring snapshot of recent studies published by scientists at the Broad Institute and their collaborators.
Genetic screening the mouse brain in vivo
Mary Wertz, core institute member Myriam Heiman, and colleagues have developed the first method for genome-wide genetic screens of the mammalian central nervous system (CNS) in vivo using both shRNA and CRISPR libraries. Reporting in Neuron, the team used the approach to identify many essential genes in neurons in the mouse brain. They also found genes that modify the toxicity of mutant Huntingin protein in two mouse models of Huntington’s disease. These included several Nme genes and others involved in chromatin silencing and dopamine signaling, pointing to potential new therapeutic targets. Learn more at MIT News.
Ticks carry many bacterial and viral pathogens, but we know little about how different microbes mix and interact within them. Such knowledge could help foster more effective control strategies. In Frontiers in Genetics, Gaurav Chauhan, Vertebrate Genomics Group director Elinor Karlsson, and colleagues describe Project Acari, a citizen science project aimed at collecting large numbers of ticks and looking for patterns in the pathogens and microbiome species they carry. In a 192-tick pilot, the team found relationships between the Lyme disease pathogen Borrelia burgdorferi and specific microbial taxa, but not with the overall diversity of a tick's microbiome.
Micro-scaled proteogenomic analysis of tumors
Cancer proteogenomics promises new insights into cancer biology and treatment by integrating genomics, transcriptomics, and protein profiling data, including phosphorylation. However, this type of analysis has only been possible in the past with relatively large tissue samples taken at surgery. In Nature Communications, a team led by research scientist Shankha Satpathy, institute scientist and Broad Proteomics Platform senior director Steven Carr, and colleagues from Baylor College of Medicine reports a new proteogenomics approach that is “micro-scaled” for efficient use on single-needle core biopsy samples from a patient’s tumor. The work provides more detail into cancer biology, tumor type, and therapy response. Read more in a news story from Baylor.
Some HIV-1-infected patients carry low levels of virus because of broadly neutralizing antibodies (bnAbs), proteins required for effective vaccine response. A team led by associated scientist Xu Yu and Enrique Martin-Gayo (Ragon Institute), in collaboration with affiliate member Mathias Lichterfeld, associate member Bruce Walker, and institute scientist Alex Shalek, identified a subgroup of HIV-1 controllers who mount potent bnAbs against the virus. Described in Cell Reports, the study showed that these patients’ dendritic cells, T cells, and monocytes have distinct transcriptional “fingerprints” and function in tightly regulated networks that promote the development of bnAbs. The work could help inform the design of future bnAb-based preventive vaccines.