Enhancing Grant-Writing Expertise in BUILD Institutions: Building Infrastructure Leading to Diversity

Background The lack of race/ethnic and gender diversity in grants funded by the National Institutes of Health (NIH) is a persistent challenge related to career advancement and the quality and relevance of health research. We describe pilot programs at nine institutions supported by the NIH-sponsored Building Infrastructure Leading to Diversity (BUILD) program aimed at increasing diversity in biomedical research. Methods We collected data from the 2016–2017 Higher Education Research Institute survey of faculty and NIH progress reports for the first four years of the program (2015–2018). We then conducted descriptive analyses of data from the nine BUILD institutions that had collected data and evaluated which activities were associated with research productivity. We used Poisson regression and rate ratios of the numbers of BUILD pilots funded, students included, abstracts, presentations, publications, and submitted and funded grant proposals. Results Teaching workshops were associated with more abstracts (RR 4.04, 95% CI 2.21–8.09). Workshops on grant writing were associated with more publications (RR 2.64, 95% CI 1.64–4.34) and marginally with marginally more presentations. Incentives to develop courses were associated with more abstracts published (RR 4.33, 95% CI 2.56–7.75). Workshops on research skills and other incentives were not associated with any positive effects. Conclusions Pilot interventions show promise in supporting diversity in NIH-level research. Longitudinal modeling that considers time lags in career development in moving from project development to grants submissions can provide more direction for future diversity pilot interventions

Rifamycin Biosynthetic Congeners: Isolation and Total Synthesis of Rifsaliniketal and Total Synthesis of Salinisporamycin and Saliniketals A and B

We describe the isolation, structure elucidation, and total synthesis of the novel marine natural product rifsaliniketal and the total synthesis of the structurally related variants salinisporamycin and saliniketals A and B. Rifsaliniketal was previously proposed, but not observed, as a diverted metabolite from a biosynthetic precursor to rifamycin S. Decarboxylation of rifamycin provides salinisporamycin, which upon truncation with loss of the naphthoquinone ring leads to saliniketals. Our synthetic strategy hinged upon a Pt­(II)-catalyzed cycloisomerization of an alkynediol to set the dioxabicyclo[3.2.1]­octane ring system and a fragmentation of an intermediate dihydropyranone to forge a stereochemically defined (<i>E</i>,<i>Z</i>)-dienamide unit. Multiple routes were explored to assemble fragments with high stereocontrol, an exercise that provided additional insights into acyclic stereocontrol during stereochemically complex fragment-assembly processes. The resulting 11–14 step synthesis of saliniketals then enabled us to explore strategies for the synthesis and coupling of highly substituted naphthoquinones or the corresponding naphthalene fragments. Whereas direct coupling with naphthoquinone fragments proved unsuccessful, both amidation and C–N bond formation tactics with the more electron-rich naphthalene congeners provided an efficient means to complete the first total synthesis of rifsaliniketal and salinisporamycin

Virtual BUILD Research Collaboratory: A biomedical data science training using innovative pedagogy to address structures of racism and inequitable stress for undergraduates of color.

ObjectiveThe unprecedented events of 2020 required a pivot in scientific training to better prepare the biomedical research workforce to address global pandemics, structural racism, and social inequities that devastate human health individually and erode it collectively. Furthermore, this pivot had to be accomplished in the virtual environment given the nation-wide lockdown.MethodsThese needs and context led to leveraging of the San Francisco Building Infrastructure Leading to Diversity (SF BUILD) theories of change to innovate a Virtual BUILD Research Collaboratory (VBRC). The purpose of VBRC was to train Black, Indigenous, and people of color (BIPOC) students to apply their unique perspectives to biomedical research. These training activities were evaluated using a pre-post survey design that included both validated and new psychosocial scales. A new scale was piloted to measure culturally relevant pedagogy.ResultsVBRC scholars increased science identity on two items: thinking of myself as a scientist (+1point, p = 0.006) and belonging to a community of scientists (+1point, p = 0.069). Overall, scholars perceived stress also decreased over VBRC (-2.35 points, p = 0.02). Post VBRC, scholars had high agency scores (μ = 11.02, Md = 12, range = 6-12, σ = 1.62) and cultural humility scores (μ = 22.11, Md = 23, range = 12-24, σ = 2.71). No notable race/ethnic differences were found in any measures.ConclusionsTaken together, our innovative approach to data science training for BIPOC in unprecedented times shows promise for better preparing the workforce critically needed to address the fundamental gaps in knowledge at the intersection of public health, structural racism, and biomedical sciences

Using Functional Signature Ontology (FUSION) to Identify Mechanisms of Action for Natural Products

A challenge for biomedical research is the development of pharmaceuticals that appropriately target disease mechanisms. Natural products can be a rich source of bioactive chemicals for medicinal applications but can act through unknown mechanisms and can be difficult to produce or obtain. To address these challenges, we developed a new marine-derived, renewable natural products resource and a method for linking bioactive derivatives of this library to the proteins and biological processes that they target in cells. We used cell-based screening and computational analysis to match gene expression signatures produced by natural products to those produced by small interfering RNA (siRNA) and synthetic microRNA (miRNA) libraries. With this strategy, we matched proteins and miRNAs with diverse biological processes and also identified putative protein targets and mechanisms of action for several previously undescribed marine-derived natural products. We confirmed mechanistic relationships for selected siRNAs, miRNAs, and compounds with functional roles in autophagy, chemotaxis mediated by discoidin domain receptor 2, or activation of the kinase AKT. Thus, this approach may be an effective method for screening new drugs while simultaneously identifying their targets

Culturally relevant pedagogy constructs for the Virtual BUILD Research Collaboratory 2020.

Culturally relevant pedagogy constructs for the Virtual BUILD Research Collaboratory 2020.</p

Median science identity and intent to pursue bioinformatics for the Virtual BUILD Research Collaboratory 2020.

Median science identity and intent to pursue bioinformatics for the Virtual BUILD Research Collaboratory 2020.</p

Engagement speakers and topics for the virtual BUILD Research Collaboratory 2020.

Engagement speakers and topics for the virtual BUILD Research Collaboratory 2020.</p

Demographic characteristics of the Virtual BUILD Research Collaboratory 2020.

Demographic characteristics of the Virtual BUILD Research Collaboratory 2020.</p

Evaluation measures for the Virtual BUILD Research Collaboratory 2020.

Evaluation measures for the Virtual BUILD Research Collaboratory 2020.</p

Elements of culturally responsive pedagogy in VBRC.

Elements of culturally responsive pedagogy in VBRC.</p