Strategies for Shared Research Resources for Enhancing Research Sustainability: Communicating Between Stakeholders and Managing Expectations to Maximize Value and Impact.

Shared research resources occupy a unique role in the scientific research landscape. Sometimes called core facilities, shared research resources provide instrumentation, services, and expertise to a wide range of researchers. With dedicated staff maintaining instruments, training users, and supporting collaborations, these resources are well situated to churn out reproducible high-quality data, lead research innovation, create efficiencies, and stimulate economic development all while driving down capital costs for institutions. That being said, in the high-paced disciplines of science with limited resources and competing priorities, these resources are often obligated to demonstrate their worth, especially beyond traditional service delivery models. How can shared research resources quantify and communicate their value and impact to stakeholders for optimal support and sustainability? For best approaches towards value proposition, it is important to understand the various stakeholders in the shared research resource ecosystem, including their needs, expectations, and value systems. This will in turn inform models of support and best approaches for planning, positioning, managing, evaluating, and improving shared research resource output to return the most value to all stakeholders involved. It is imperative that communication is tailored for each unique group of stakeholders, and terminology and expectations are managed accordingly. This work attempts to curate and share approaches and best practices toward this effort, gathered through available literature and focused engagement with various shared research resource stakeholders.

A Shift in Our Thinking: Reframing Shared Research Resources as Investments in Education and Innovation, Not Subsidized Science.

For many researchers, Shared Research Resources are often the most cost-effective means of using state-of-the-art (not to mention expensive) instrumentation. Along with access to the instruments themselves, Shared Research Resources also offer individualized training by highly qualified Shared Research Resource staff-again at deeply discounted costs compared to the operational costs of the facilities. Traditionally, this gap in revenue has been termed a subsidy. But, as with many words, connotation matters, and we posit that this language ought to be changed to reframe our thinking and impart the true impact of Shared Research Resources. We argue here that rather than a subsidy, the revenue gap is better described as an investment. Furthermore, investments of Shared Research Resources lead to positive externalities, including education and innovation.

Establishing a national strategy for shared research resources in biomedical sciences.

Contemporary science has become increasingly multi-disciplinary and team-based, resulting in unprecedented growth in biomedical innovation and technology over the last several decades. Collaborative research efforts have enabled investigators to respond to the demands of an increasingly complex 21st century landscape, including pressing scientific challenges such as the COVID-19 pandemic. A major contributing factor to the success of team science is the mobilization of core facilities and shared research resources (SRRs), the scientific instrumentation and expertise that exist within research organizations that enable widespread access to advanced technologies for trainees, faculty, and staff. For over 40 years, SRRs have played a key role in accelerating biomedical research discoveries, yet a national strategy that addresses how to leverage these resources to enhance team science and achieve shared scientific goals is noticeably absent. We believe a national strategy for biomedical SRRs-led by the National Institutes of Health-is crucial to advance key national initiatives, enable long-term research efficiency, and provide a solid foundation for the next generation of scientists.

Nitrosyl hydride (HNO) replaces dioxygen in nitroxygenase activity of manganese quercetin dioxygenase.

Quercetin dioxygenase (QDO) catalyzes the oxidation of the flavonol quercetin with dioxygen, cleaving the central heterocyclic ring and releasing CO. The QDO from Bacillus subtilis is unusual in that it has been shown to be active with several divalent metal cofactors such as Fe, Mn, and Co. Previous comparison of the catalytic activities suggest that Mn(II) is the preferred cofactor for this enzyme. We herein report the unprecedented substitution of nitrosyl hydride (HNO) for dioxygen in the activity of Mn-QDO, resulting in the incorporation of both N and O atoms into the product. Turnover is demonstrated by consumption of quercetin and other related substrates under anaerobic conditions in the presence of HNO-releasing compounds and the enzyme. As with dioxygenase activity, a nonenzymatic base-catalyzed reaction of quercetin with HNO is observed above pH 7, but no enhancement of this basal reactivity is found upon addition of divalent metal salts. Unique and regioselective N-containing products ((14)N/(15)N) have been characterized by MS analysis for both the enzymatic and nonenzymatic reactions. Of the several metallo-QDO enzymes examined for nitroxygenase activity under anaerobic condition, only the Mn(II) is active; the Fe(II) and Co(II) substituted enzymes show little or no activity. This result represents an enzymatic catalysis which we denote nitroxygenase activity; the unique reactivity of the Mn-QDO suggests a metal-mediated electron transfer mechanism rather than metal activation of the substrate's inherent base-catalyzed reactivity.