The Joint Safety Team (JST) was conceived in 2012 by the Departments of Chemical Engineering and Materials Science and Chemistry at the University of Minnesota and the Dow Chemical Company as a model student-led safety organization. The JST initiative was aimed at improving academic safety through four core areas: compliance, awareness, resources, and education. Since its inception, the JST has taken great strides to develop a culture of peer-led safety at Minnesota. We describe the evolution of the structure of the organization over the last 8 years and the innovative methodologies employed by the JST to educate and evaluate safety in academic laboratories. The continuous efforts of the student members of the JST have enabled the organization to be recognized as a leader in peer-to-peer safety. The Minnesota model of “inform and reform” is now being adopted at other academic institutions to develop safety organizations emulating the JST.

Photoremovable caging groups are useful for biological applications since the deprotection process can be initiated by illumination with light without the necessity of adding additional reagents such as acids or bases that can perturb biological activity. In solid phase peptide synthesis (SPPS), the most common photoremovable group used for thiol protection is the o-nitrobenzyl group and related analogues. In earlier work, we explored the use of the nitrodibenzofuran (NDBF) group for thiol protection and found it to exhibit a faster rate towards UV photolysis relative to simple nitroveratryl-based protecting groups and a useful two-photon cross-section. Here we describe the synthesis of a new NDBF-based protecting group bearing a methoxy substituent and use it to prepare a protected form of cysteine suitable for SPPS. This reagent was then used to assemble two biologically relevant peptides and characterize their photolysis kinetics in both UV-and twophoton-mediated reactions; a two-photon action cross-section of 0.71 -1.4 GM for the new protecting group was particularly notable. Finally, uncaging of these protected peptides by either UV or two-photon activation was used to initiate their subsequent enzymatic processing by the enzyme farnesyltransferase. These experiments highlight the utility of this new protecting group for SPPS and biological experiments.

Laboratory safety teams (LSTs), led by graduate student and postdoctoral researchers, have been propagating across the U.S. as a bottom-up approach to improving safety culture in academic research laboratories. Prior to the COVID-19 pandemic, LSTs relied heavily on in-person projects and events. Additionally, committed Champions from the ranks of safety professionals and faculty were critical to their operation and continued expansion. As was the case for many existing systems, the COVID-19 global crisis served as an operational stress test for LSTs, pushing them to unexpected new limits. The initial spread of COVID-19 brought with it a shutdown of academic institutions followed by a limited reopening that prohibited in-person gatherings and disrupted standard lines of communication upon which LSTs relied. Safety professionals and faculty members were required to take on new duties that were often undefined and time-consuming, substantially impacting their ability to support LSTs. In this case study, we report the impact of this operational stress test on 12 LSTs, detailing the adaptive means by which they survived and highlighting the key lessons learned by the represented LST leaders. The key takeaways were to spend time nurturing relationships with a diverse array of Champions, securing stable funding from multiple sources, and networking with members of LSTs from different institutions to strengthen moral support and broaden ideation for common challenges.

A 3-nitrodibenzofuran cure provides blue-shifted reactivity in vinylogous photocleavage processes.

Photoswitchable lipids have emerged as attractive tools for the optical control of lipid bioactivity, metabolism, and biophysical properties. Their design is typically based on the incorporation of an azobenzene photoswitch into the hydrophobic lipid tail, which can be switched between its trans- and cis-form using two different wavelengths of light. While glycero- and sphingolipids have been successfully designed to be photoswitchable, isoprenoid lipids have not yet been investigated. Herein, we describe the development of photoswitchable analogs of an isoprenoid lipid and systematically assess their potential for the optical control of various steps in the isoprenylation processing pathway of CaaX proteins in Saccharomyces cerevisiae. One photoswitchable analog of farnesyl diphosphate (AzoFPP-1) allowed effective optical control of substrate prenylation by farnesyltransferase. The subsequent steps of isoprenylation processing (proteolysis by either Ste24 or Rce1 and carboxyl methylation by Ste14) were less affected by photoisomerization of the group introduced into the lipid moiety of the substrate a-factor, a mating pheromone from yeast. We assessed both proteolysis and methylation of the a-factor analogs in vitro and the bioactivity of a fully processed a-factor analog containing the photoswitch, exogenously added to cognate yeast cells. Combined, these data describe the first successful conversion of an isoprenoid lipid into a photolipid and suggest the utility of this approach for the optical control of protein prenylation.