Pharmacy education faces significant challenges, particularly in keeping up with the rapidly evolving health care landscape due to the expansion of information and technology. The pressure to "teach everything" risks curriculum overload and detracts from defining core knowledge essential for pharmacists. This commentary advocates for a comprehensive definition of pharmacist knowledge as a framework to reorganize pharmacy education, aligning with knowledge domains outlined by the Organization for Economic Cooperation and Development. It proposes the Baumkuchen Layer Model, a metaphor inspired by the German layer cake, to integrate academic discipline classification with a hierarchical knowledge structure. This approach ensures a solid foundation for students, enabling them to engage with increasingly complex concepts, thus preparing them to navigate modern health care complexities, contribute to patient care, and support public health initiatives.

Introduction: Faculty workload policy has gained increased attention recently given the growing amount of faculty burnout leading to decreased productivity, worsened faculty morale, and impaired retention. Faculty are one of the most valuable resources of an academic institution; thus, it is essential that a clear picture of the "jobs to be done" are defined and valued. Perspective: The approach of a task force charged with developing a teaching workload policy is described. Through this work, it was recognized that essential roles of the contemporary pharmacy educator have not been defined, resulting in workload policies that might only value and recognize "traditional" educator roles. This led the task force to evaluate the forces driving change in education and to identify the roles of faculty as educators. The stepwise approach used to define nine essential roles of contemporary pharmacy educators is described. Implications: Roles of the educator have become more complex, and traditional definitions of these roles do not recognize and value the multifaceted nature of the job to be done. Consideration of contemporary definitions of educator roles is a critical first step for developing workload policies. The new definition of educator roles will allow the academic institution to have more clarity

Purpose: Faculty teaching workload has become a focus for many academic institutions given the increasing amount of faculty burnout and need for equitable distribution of effort. Many gaps exist in faculty workload guidance which contribute to decreased faculty productivity, lack of appropriate recognition, faculty burnout, and subsequently, retention of faculty. A task force was created to develop teaching workload guidance and to outline minimum teaching expectations at our school of pharmacy. Description: This manuscript highlights the need for clarity around the definition of roles of the contemporary educator and considerations when developing guidance around teaching workload expectations using the "What? So What? Now What? " reflection framework. Analysis/interpretation: Teaching workload guidance first starts with establishing a definition of the contemporary roles of the educator. Challenges, considerations, and eight next steps are outlined that are critical to address before equitable teaching workload guidance is established. Conclusions: Teaching workload guidance should include transparency, clarity, credit, norms, context, and accountability. Additionally, solutions created to address the gaps in workload policies should be data driven.

In pharmacy education, we are experiencing the “new normal” after an “inflection point” along with a host of other overused phrases. Yet, without doubt, there is pressing need to reconsider what was once standard operating procedure. When an inflection point is viewed as opportunity, it sparks a strategic boom. Indeed, the confluence of threats and opportunities caused—or revealed—by the COVID‐19 pandemic is setting the stage for an acceleration of change in professional education. In this paper, we investigate the motivations and approaches to accelerate needed change in pharmacy education. Though prompted by the demand for rapid restructuring in response to the COVID‐19 pandemic, these ideas transcend any one driver. We argue that now is the time to disrupt current practices through innovation leading to new educational models and present sample solutions. We consider academic, social, technological, economic, and political (ASTEP) forces driving the imperative to educational change.

The UNC Eshelman School of Pharmacy is transforming its doctor of pharmacy program to emphasize active engagement of students in the classroom, foster scientific inquiry and innovation, and immerse students in patient care early in their education. The admissions process is also being reengineered.

The human commensal pathogen Streptococcus pneumoniae expresses a number of virulence factors that promote serious pneumococcal diseases, resulting in significant morbidity and mortality worldwide. These virulence factors may give S. pneumoniae the capacity to escape immune defenses, resist antimicrobial agents, or a combination of both. Virulence factors also present possible points of therapeutic intervention. The activities of the surface endonuclease, EndA, allow S. pneumoniae to establish invasive pneumococcal infection. EndA’s role in DNA uptake during transformation contributes to gene transfer and genetic diversification. Moreover, EndA’s nuclease activity degrades the DNA backbone of neutrophil extracellular traps (NETs), allowing pneumococcus to escape host immune responses. Given its potential impact on pneumococcal pathogenicity, EndA is an attractive target for novel antimicrobial therapy. Herein, we describe the development of a high-throughput screening assay for the discovery of nuclease inhibitors. Nuclease-mediated digestion of double-stranded DNA was assessed using fluorescence changes of the DNA dye ligand, PicoGreen. Under optimized conditions, the assay provided robust and reproducible activity data (Z′= 0.87) and was used to screen 4727 small molecules against an imidazole-rescued variant of EndA. In total, six small molecules were confirmed as novel EndA inhibitors, some of which may have utility as research tools for understanding pneumococcal pathogenesis and for drug discovery.

Signal transduction, regulatory processes and pharmaceutical responses are highly dependent upon ligand residence times. Gaining insight into how physical factors influence residence times (1/k(off)) should enhance our ability to manipulate biological interactions. We report experiments that yield structural insight into k(off) involving a series of eight 2,4-diaminopyrimidine inhibitors of dihydrofolate reductase whose binding affinities vary by six orders of magnitude. NMR relaxation-dispersion experiments revealed a common set of residues near the binding site that undergo a concerted millisecond-timescale switching event to a previously unidentified conformation. The rate of switching from ground to excited conformations correlates exponentially with the binding affinity K(i) and k(off), suggesting that protein dynamics serves as a mechanical initiator of ligand dissociation within this series and potentially for other macromolecule-ligand systems. Although the forward rate of conformational exchange, k(conf,forward), is faster than k(off), the use of the ligand series allowed for connections to be drawn between kinetic events on different timescales.

Structure-based drug design relies on static protein structures despite significant evidence for the need to include protein dynamics as a serious consideration. In practice, dynamic motions are neglected because they are not understood well enough to model, a situation resulting from a lack of explicit experimental examples of dynamic receptor-ligand complexes. Here, we report high-resolution details of pronounced ~1 ms time scale motions of a receptor-small molecule complex using a combination of NMR and X-ray crystallography. Large conformational dynamics in Escherichia coli dihydrofolate reductase are driven by internal switching motions of the drug-like, nanomolar-affinity inhibitor. Carr-Purcell-Meiboom-Gill relaxation dispersion experiments and NOEs revealed the crystal structure to contain critical elements of the high energy protein-ligand conformation. The availability of accurate, structurally resolved dynamics in a protein-ligand complex should serve as a valuable benchmark for modeling dynamics in other receptor-ligand complexes and prediction of binding affinities.

The activities of the bacterial RecA protein are involved in the de novo development and transmission of antibiotic resistance genes, thus allowing bacteria to overcome the metabolic stress induced by antibacterial agents. RecA is ubiquitous and highly conserved among bacteria, but has only distant homologs in human cells. Together, this evidence points to RecA as a novel and attractive antibacterial drug target. All known RecA functions require the formation of a complex formed by multiple adenosine 5'-O-triphosphate (ATP)-bound RecA monomers on single-stranded DNA. In this complex, RecA hydrolyzes ATP. Although several methods for assessing RecA's ATPase activity have been reported, these assay conditions included relatively high concentrations of enzyme and ATP and thereby restricted the RecA conformational state. Herein, we describe the validation of commercial reagents (Transcreener(®) adenosine 5'-O-diphosphate [ADP](2) fluorescence polarization assay) for the high-throughput measurement of RecA's ATPase activity with lower concentrations of ATP and RecA. Under optimized conditions, ADP detection by the Transcreener reagent provided robust and reproducible activity data (Z'=0.92). Using the Transcreener assay, we screened 113,477 small molecules against purified RecA protein. In total, 177 small molecules were identified as confirmed hits, of which 79 were characterized by IC(50) values ≤ 10 μM and 35 were active in bioassays with live bacteria. This set of compounds comprises previously unidentified scaffolds for RecA inhibition and represents tractable hit structures for efforts aimed at tuning RecA inhibitory activity in both biochemical and bacteriological assays.

The bacterial RecA protein has been implicated as a bacterial drug target not as an antimicrobial target, but as an adjuvant target with the potential to suppress the mechanism by which bacteria gain drug resistance. In order to identify small molecules that inhibit RecA/ssDNA nucleoprotein filament formation, we have adapted the phosphomolybdate-blue ATPase assay for high throughput screening to determine RecA ATPase activity against a library of 33,600 compounds, which is a selected representation of diverse structure of 350,000. Four distinct chemotypes were represented among the 40 validated hits. SAR and further chemical synthesis is underway to optimize this set of inhibitors to be used as antimicrobial adjuvant agents.

The phenomenon of antibiotic resistance has created a need for the development of novel antibiotic classes with nonclassical cellular targets.Unfortunately, target-based drug discovery against proteins considered essential for in vitro bacterial viability has yielded few new therapeutic classes of antibiotics.Targeting the large proportion of genes considered nonessential that have yet to be explored by high-throughput screening, for example, RecA, can complement these efforts.Recent evidence suggests that RecA-controlled processes are responsible for tolerance to antibiotic chemotherapy and are involved in pathways that ultimately lead to full-fledged antibiotic resistance.Therefore inhibitors of RecA may serve as therapeutic adjuvants in combination chemotherapy of bacterial infectious diseases.Toward the goal of validating RecA as a novel target in the chemotherapy of bacterial infections, the authors have screened 35,780 small molecules against RecA.In total, 80 small molecules were identified as primary hits and could be clustered in 6 distinct chemotype clades.The most potent class of hits was further examined, and 1 member compound was found to inhibit RecA-mediated strand exchange and prevent ciprofloxacin-induced SOS expression in Escherichia coli.This compound represents the first small molecule demonstrating an ability to inhibit the bacterial SOS response in live bacterial cell cultures.(

Bacterial RecA promotes the development and transmission of antibiotic resistance genes by self-assembling into an ATP-hydrolyzing filamentous homopolymer on single-stranded DNA. We report the design of a 29mer peptide based on the RecA N-terminal domain involved in intermonomer contact that inhibits RecA filament assembly with an IC50 of 3 mu M.

The RecA protein of Escherichia coli plays a crucial roles in DNA recombination and repair, as well as various aspects of bacterial pathogenicity. The formation of a RecA-ATP-ssDNA complex initiates all RecA activities and yet a complete structural and mechanistic description of this filament has remained elusive. An analysis of RecA-DNA interactions was performed using fluorescently labeled oligonucleotides. A direct comparison was made between fluorescein and several fluorescent nucleosides. The fluorescent guanine analog 6-methylisoxanthopterin (6MI) demonstrated significant advantages over the other fluorophores and represents an important new tool for characterizing RecA-DNA interactions.

The roles of bacterial RecA in the evolution and transmission of antibiotic resistance genes make it an attractive target for inhibition by small molecules. We report two complementary fluorescence-based ATPase assays that were used to screen for inhibitors of RecA. We elected to employ the ADP-linked variation of the assay, with a Z' factor of 0.83 in 96-well microplates, to assess whether 18 select compounds could inhibit ATP hydrolysis by RecA. The compounds represented five sets of related inhibitor scaffolds, each of which had the potential to cross-inhibit RecA. Although nucleotide analogs, known inhibitors of GHL ATPases, and known protein kinase inhibitors were not active against RecA, we found that three suramin-like agents substantially inhibited RecA's ATPase activity. (c) 2007 Elsevier Ltd. All rights reserved.