Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair.

Homology Directed Repair (HDR) enables precise genome editing, but the implementation of HDR-based therapies is hindered by limited efficiency in comparison to methods that exploit alternative DNA repair routes, such as Non-Homologous End Joining (NHEJ). In this study, we develop a functional, pooled screening platform to identify protein-based reagents that improve HDR in human hematopoietic stem and progenitor cells (HSPCs). We leverage this screening platform to explore sequence diversity at the binding interface of the NHEJ inhibitor i53 and its target, 53BP1, identifying optimized variants that enable new intermolecular bonds and robustly increase HDR.

Different factors limit early- and late-season windows of opportunity for monarch development.

Seasonal windows of opportunity are intervals within a year that provide improved prospects for growth, survival, or reproduction. However, few studies have sufficient temporal resolution to examine how multiple factors combine to constrain the seasonal timing and extent of developmental opportunities. Here, we document seasonal changes in milkweed ()-monarch () interactions with high resolution throughout the last three breeding seasons prior to a precipitous single-year decline in the western monarch population.

Genetic Determinants of Intrinsic Antibiotic Tolerance in Mycobacterium avium.

The Mycobacterium avium complex (MAC) is one of the most prevalent causes of nontuberculous mycobacteria pulmonary infection in the United States, and yet it remains understudied. Current MAC treatment requires more than a year of intermittent to daily combination antibiotic therapy, depending on disease severity. In order to shorten and simplify curative regimens, it is important to identify the innate bacterial factors contributing to reduced antibiotic susceptibility, namely, antibiotic tolerance genes.