A First-in-Class High-Throughput Screen to Discover Modulators of the Alternative Lengthening of Telomeres (ALT) Pathway.

Telomeres are a protective cap that prevents chromosome ends from being recognized as double-stranded breaks. In somatic cells, telomeres shorten with each cell division due to the end replication problem, which eventually leads to senescence, a checkpoint proposed to prevent uncontrolled cell growth. Tumor cells avoid telomere shortening by activating one of two telomere maintenance mechanisms (TMMs): telomerase reactivation or alternative lengthening of telomeres (ALT).

Behind the screen: drug discovery using the big data of phenotypic analysis.

Technological advances in drug discovery are exciting to students, but it is challenging for faculty to maintain the pace with these developments, particularly within undergraduate courses. In recent years, a High-throughput Discovery Science and Inquiry-based Case Studies for Today's Students (HITS) Research Coordination Network has been assembled to address the mechanism of how faculty can, on-pace, introduce these advancements. As a part of HITS, our team has developed "Behind the Screen: Drug Discovery using the Big Data of Phenotypic Analysis" to introduce students and faculty to phenotypic screening as a tool to identify inhibitors of diseases that do not have known cellular targets.

Nuclear actin structure regulates chromatin accessibility.

Polymerized β-actin may provide a structural basis for chromatin accessibility and actin transport into the nucleus can guide mesenchymal stem cell (MSC) differentiation. Using MSC, we show that using CK666 to inhibit Arp2/3 directed secondary actin branching results in decreased nuclear actin structure, and significantly alters chromatin access measured with ATACseq at 24 h. The ATAC-seq results due to CK666 are distinct from those caused by cytochalasin D (CytoD), which enhances nuclear actin structure.