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.

Implementing an effective software solution is an important step in managing a portfolio of core facilities. Though commercial options are available, developing or adopting a custom platform is a viable path for many institutions. At Northwestern University (NU), the cores program was reorganized beginning in 2008, and we pursued the latter path in order to retain control of the development priorities and to ensure integration with other enterprise systems. This manuscript describes our experience and results after a decade of effort. The platform, named NUcore, began enrollment in 2011, and full enrollment was achieved in 2019. Key features of NUcore include a stable and secure environment, a responsive and intuitive interface for users and core staff, seamless integration with the university financial system, rules and restrictions to ensure compliance, and both core-specific and enterprise reporting. NUcore now supports nearly half of all sponsored award dollars at NU at a cost of only 1 cent per dollar of business transacted. On average, there are over 4000 active users each year. NUcore is managed as an open-source project, available at no cost to any organization. Five academic organizations currently use the NUcore code base. For NU, NUcore has been a substantial success, and continuous development will ensure that it meets the future needs of our university and its cores.

President Biden’s renewed push to develop cures for society’s most devastating diseases including cancer and Alzheimer’s, in tandem with infrastructure investments to “Build Back Better,” represents an opportunity to harness our nation’s critical shared research resources (SRRs). For over 40 years, SRRs have played a key role in accelerating biomedical research discoveries and innovations by providing widespread access to cutting-edge technologies, services, and scientific expertise. Yet a national strategy that addresses how to leverage these resources to ensure new treatments, cures, and economic vitality is noticeably absent. A national strategy for SRRs—led by the National Institutes of Health (NIH)—is crucial to advance key national initiatives and enable long-term efficiency, coordination, and economic impact of these critical assets.

ddressing the needs of women in the life science workforce can improve work–life integration and contribute to a more diverse and inclusive world economy.

Core facilities are an integral component of modern research institutions. Here, we describe our efforts over the past decade to build a sustainable portfolio of core facilities at Northwestern University. Through careful strategic planning, coordination, investment, and oversight, we have developed a model for managing core facilities that addresses researchers' needs within 3 schools across 2 campuses. Our management model is a partnership between core directors and central administrators that maintains operational control of each facility at the local level to ensure that the needs of researchers are being addressed. Central administrative oversight ensures that facilities are compliant with federal regulations, are financially sound, and align with institutional priorities. This hybrid management model is comprised of 4 pillars that are essential and necessary to ensure the long-term viability and success of facilities: core personnel, core space, institutional investment, and institutional evaluation. With these pillars in place, our facilities are well positioned to fulfill their key value propositions, to demonstrate a robust return on the university's investment, and to ensure that facilities remain vibrant, sustainable components of the research ecosystem for the foreseeable future.

Core Facilities are key elements in the research portfolio of academic and private research institutions. Administrators overseeing core facilities (core administrators) require assessment tools for evaluating the need and effectiveness of these facilities at their institutions. This article discusses ways to promote best practices in core facilities as well as ways to evaluate their performance across 8 of the following categories: general management, research and technical staff, financial management, customer base and satisfaction, resource management, communications, institutional impact, and strategic planning. For each category, we provide lessons learned that we believe contribute to the effective and efficient overall management of core facilities. If done well, we believe that encouraging best practices and evaluating performance in core facilities will demonstrate and reinforce the importance of core facilities in the research and educational mission of institutions. It will also increase job satisfaction of those working in core facilities and improve the likelihood of sustainability of both facilities and personnel.

This presentation will provide an update on two inter-institutional initiatives involving core facilities. The Open Access Initiative among Northwestern, the University of Chicago and the University of Illinois-Chicago was spearheaded by a study conducted by Huron Education. It resulted in a Memorandum of Understanding that allows researchers at each university to use each other's core facilities seamlessly. This means that researchers are treated the same in regard to availability and pricing of equipment and services regardless of their home institution. The second initiative is the formation of a Core Facility Working Group among Big Ten Universities and the University of Chicago. The purpose of this Group is to share best practices, facilitate regional collaborations, and enhance professional development.

Digital image processing utilizes computer-aided enhancement to turn subjective features of an image into data that can be measured, quantified and evaluated. The first step in this process is deciding what features are of interest and tractable. This presentation will address how optical illusions distort and fabricate features due to fundamental properties of human visual perception. Examples of common illusions generated by microscope-based imaging systems will be described as well as ways in which to avoid or account for them.

This article addresses the growing interest among U.S. scientific organizations and federal funding agencies in strengthening research partnerships between American universities and the private sector. It outlines how core facilities at universities can contribute to this partnership by offering services and access to high-end instrumentation to both nonprofit organizations and commercial organizations. We describe institutional policies (best practices) and procedures (terms and conditions) that are essential for facilitating and enabling such partnerships. In addition, we provide an overview of the relevant federal regulations that apply to external use of academic core facilities and offer a set of guidelines for handling them. We conclude by encouraging directors and managers of core facilities to work with the relevant organizational offices to promote and nurture such partnerships. If handled appropriately, we believe such partnerships can be a win-win situation for both organizations that will support research and bolster the American economy.

Tetramethylrhodamine methyl ester (TMRM) is a fluorescent dye used to study mitochondrial function in living cells. Previously, we reported that TMRM effectively labeled mitochondria of neurons deep within mouse brain slices. Use of micromolar concentration of dye, which was required to get sufficient staining for two-photon imaging, resulted in typical fluctuations of TMRM. With prolonged exposure, we recorded additional responses in some neurons that included slow oscillations and propagating waves of fluorescence. (Note: We use the terms "fluctuation" to refer to a change in the fluorescent state of an individual mitochondrion, "oscillation" to refer to a localized change in fluorescence in the cytosol, and "wave" to refer to a change in cytosolic fluorescence that propagated within a cell. Use of these terms does not imply any underlying periodicity.) In this report we describe similar results using cultured rat hippocampal neurons. Prolonged exposure of cultures to 2.5 µM TMRM produced a spontaneous increase in fluorescence in some neurons, but not glial cells, after 45-60 minutes that was followed by slow oscillations, waves, and eventually apoptosis. Spontaneous increases in fluorescence were insensitive to high concentrations of FCCP (100 µM) and thapsigargin (10 µM) indicating that they originated, at least in part, from regions outside of mitochondria. The oscillations did not correlate with changes in intracellular Ca(2+), but did correlate with differences in fluorescence lifetime of the dye. Fluorescence lifetime and one-photon ratiometric imaging of TMRM suggested that the spontaneous increase and subsequent oscillations were due to movement of dye between quenched (hydrophobic) and unquenched (hydrophilic) compartments. We propose that these movements may be correlates of intracellular events involved in early stages of apoptosis.

The CAN-CC was established by the ABRF in 2010 to facilitate greater interaction among core scientists and administrators and with the goal of creating a set of references, procedures and best practices for institutions engaged in core facility management and oversight. In particular, we seek to develop a database of core administrators, identify and describe core management model systems, and identify, collect and describe tools for core administration. Here we summarize results from our first survey, representing responses of 172 individuals from 79 institutions. The data highlights the demographics of core facility management/administration; issues of interest to individuals involved in the various areas of core management, scientific oversight and/or administration; and identification of the overall factors and characteristics common to most cores.

The adult brain subventricular zone (SVZ) produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulb (OB) in a specialized niche. Galectin-3 (Gal-3) regulates proliferation and migration in cancer and is expressed by activated macrophages after brain injury. The function of Gal-3 in the normal brain is unknown, but we serendipitously found that it was expressed by ependymal cells and SVZ astrocytes in uninjured mice. Ependymal cilia establish chemotactic gradients and astrocytes form glial tubes, which combine to aid neuroblast migration. Whole-mount preparations and electron microscopy revealed that both ependymal cilia and SVZ astrocytes were disrupted in Gal3(-/-) mice. Interestingly, far fewer new BrdU(+) neurons were found in the OB of Gal3(-/-) mice, than in wild-type mice 2 weeks after labeling. However, SVZ proliferation and cell death, as well as OB differentiation rates were unaltered. This suggested that decreased migration in vivo was sufficient to decrease the number of new OB neurons. Two-photon time-lapse microscopy in forebrain slices confirmed decreased migration; cells were slower and more exploratory in Gal3(-/-) mice. Gal-3 blocking antibodies decreased migration and dissociated neuroblast cell-cell contacts, whereas recombinant Gal-3 increased migration from explants. Finally, we showed that expression of phosphorylated epidermal growth factor receptor (EGFR) was increased in Gal3(-/-) mice. These results suggest that Gal-3 is important in SVZ neuroblast migration, possibly through an EGFR-based mechanism, and reveals a role for this lectin in the uninjured brain.

The Midwest Association of Core Directors (MWACD) was organized in 2010 by a group of scientists at 6 different institutions to foster closer interactions among directors and managers of core facilities throughout the Central Plains. The organization shares the same goals as ABRF, and it has applied to become a chapter of ABRF. The MWACD differs from ABRF only in that its focus is on regional matters rather than on issues of national concern. Towards this goal, the first annual meeting of the MWACD took place on October 21–23, 2010, at the Crowne Plaza Hotel in Chicago. The goal of the meeting was to provide an opportunity for networking among core directors and managers, to enable interactions with colleagues, sharing of technical advice, and discussions of continuing challenges associated with the operation of shared research resources and technologies. Keynote presentations were delivered by leaders of NIH-NCRR and FASEB, and there were panel discussions on networking, bioinformatics, and information management systems. There was a poster session, vendor exhibits, and breakout sessions on 8 different core-related topics. The meeting was attended by 120 researchers and supported by 17 corporate and not-for-profit organizations.

The mission of the ABRF is to advance life sciences core facilities and biotechnology laboratories through research, communication, and education. To facilitate this mission, the ABRF has implemented ABRF Affiliates and Chapters and the ABRF Affiliates and Chapters Committee for the following purposes: a) To encourage the establishment, support the operations, and facilitate the coordination of new regional and special interest groups that have goals related to those of the ABRF in support of life sciences shared resources; b) To establish partnerships and collaborate with other existing organizations that have goals related to those of the ABRF in support of life sciences shared resources; c) To promote the technologies, research support and administration of biomolecular resource facilities; d) To promote the development and applications of biotechnologies as shared research resources and to facilitate the advancement of life sciences research; e) To play a leadership role in networking core laboratories, researchers, and students, matching those with similar and complementary interests and skills; e) To enhance communication on the regional, national and international level regarding ABRF activities; to enhance the visibility of the ABRF in the scientific community; to educate the scientific community about the value of the ABRF; and to broaden the number and diversity of core laboratories and biotechnology laboratories that take advantage of the ABRF research group studies and ABRF membership networking opportunities; and f) To enhance the visibility of the ABRF with funding agencies that support the development, acquisition and application of core facility shared research resources. ABRF Chapters are special interest groups which may be formed based on common interests and/or geographical boundaries and support grassroots networks of individuals who wish to help advance ABRF goals and promote the mission of shared resource facilities and biomolecular resources. ABRF Affiliates are special interest organizations that are autonomous from the ABRF, have common and complementary interests with the ABRF, and have the goal of developing a collaborative relationship with the ABRF. Please join us for the ABRF Affiliates and Chapters Open Mic Session from 6:00 pm to 6:45 pm on Sunday.

Neuroblasts born in the adult subventricular zone (SVZ) migrate long distances in the rostral migratory stream (RMS) to the olfactory bulbs where they integrate into circuitry as functional interneurons. As very little was known about the dynamic parameters of SVZ neuroblast migration, we used two-photon time-lapse microscopy to analyze migration in acute slices. This involved analyzing 3D stacks of images over time and uncovered several novel aspects of SVZ migration: chains remain stable, cells can be immotile for extensive periods, morphology does not necessarily correlate with motility, neuroblasts exhibit local exploratory motility, dorsoventral migration occurs throughout the striatal SVZ, and neuroblasts turn at distinctive angles. We investigated these novel findings in the SVZ and RMS from the population to the single cell level. In this review we also discuss some technical considerations when setting up a two-photon microscope imaging system. Throughout the review we identify several unsolved questions about SVZ neuroblast migration that might be addressed with current or emerging techniques.

Neuroblasts generated in the adult subventricular zone (SVZ) migrate through the rostral migratory stream (RMS) to the olfactory bulb (OB). Previous work uncovered motility ranging from straight to complex, but it was unclear if directional changes were stochastic or exhibited stereotypical patterns. Here, we provide the first in-depth two-photon time-lapse microscopy study of morphological and dynamic features that accompany turning and direction reversals in the RMS. We identified three specific kinds of turning (30-90 degrees): bending of the leading process proximal to the cell body (P-bending 47% of cases), bending of the distal leading process (D-bending 30%) or branching of the leading process or lamellipodium (23%). Bending and branching angles were remarkably constrained and were significantly different from one another. Cells reversed direction (> 90 degrees) through D-bendings (54%), branching (11%) or de novo growth of processes from the soma (23%), but not P-bending. Direction reversal was often composed of several iterations of D-bending or branching as opposed to novel modalities. Individual neuroblasts could turn or change direction in multiple patterns suggesting that the patterns are not specific for different lineages. These findings show that neuroblasts in the RMS use a limited number of distinct and constrained modalities to turn or reverse direction.

Striatal dopamine depletion profoundly reduces the density of spines and corticostriatal glutamatergic synapses formed on D(2) dopamine receptor expressing striatopallidal medium spiny neurons, leaving D(1) receptor expressing striatonigral medium spiny neurons relatively intact. Because D(2) dopamine receptors diminish the excitability of striatopallidal MSNs, the pruning of synapses could be a form of homeostatic plasticity aimed at restoring activity into a preferred range. To characterize the homeostatic mechanisms controlling synapse density in striatal medium spiny neurons, striatum from transgenic mice expressing a D(2) receptor reporter construct was co-cultured with wild-type cerebral cortex. Sustained depolarization of these co-cultures induced a profound pruning of glutamatergic synapses and spines in striatopallidal medium spiny neurons. This pruning was dependent upon Ca(2+) entry through Cav1.2 L-type Ca(2+) channels, activation of the Ca(2+)-dependent protein phosphatase calcineurin and up-regulation of myocyte enhancer factor 2 (MEF2) transcriptional activity. Depolarization and MEF2 up-regulation increased the expression of two genes linked to synaptic remodeling-Nur77 and Arc. Taken together, these studies establish a translational framework within which striatal adaptations linked to the symptoms of Parkinson's disease can be explored.

We used two-photon imaging of the fluorescent dye tetramethyl-rhodamine methyl ester (TMRM) to visualize spontaneous oscillations of mitochondrial membrane potential in cultured rat hippocampal neurons. TMRM-loaded cells displayed two distinct forms of spontaneous oscillation when imaged in artificial cerebral spinal fluid (ACSF) at room temperature: fast oscillation of individual mitochondria (flickering) corresponding to periods of depolarization lasting several seconds, and slow oscillation of groups of mitochondria (wave) corresponding to depolarizations lasting 1-3 minutes. Similar types of spontaneous oscillation have been reported previously using isolated mitochondria and cultured cells, although the underlying cause(s) of the oscillations is unclear. In isolated mitochondria, flickering can be triggered by mitochondrial Ca uptake (Biophys. J. 87: 3585, 2004) and waves can be induced by local Ca elevation (Cell 89: 1145, 1997). We tested whether Ca could exert similar effects in cultured hippocampal neurons by testing cells loaded with both TMRM and a Ca-sensitive fluorophore (fura-2 or fluo-3). Cellular fluorescence was imaged repeatedly every second for up to 60 minutes. Under our conditions (in ACSF at room temperature), neurons displayed spontaneous oscillations in both TMRM and Ca-sensitive dyes, but there was no correlation between these signals. Furthermore, some neurons displayed fast and slow TMRM oscillations without alteration in Ca levels, while others exhibited fast Ca oscillations (lasting 3-8 sec) but no TMRM oscillations. In addition, Ca oscillations were often synchronized in adjacent neurons, whereas TMRM oscillations were not. These results indicate that oscillations in cytosolic calcium levels do not appear to be directly coupled to oscillations in mitochondrial membrane potential in cultured hippocampal neurons. This does not rule out the possibility that Ca might influence mitochondrial oscillations through an indirect action.

BACKGROUND:The adult subventricular zone (SVZ) contains stem and progenitor cells that generate neuroblasts throughout life. Although it is well accepted that SVZ neuroblasts are migratory, recent evidence suggests their progenitor cells may also exhibit motility. Since stem and progenitor cells are proliferative and multipotential, if they were also able to move would have important implications for SVZ neurogenesis and its potential for repair. METHODOLOGY/PRINCIPAL FINDINGS:We studied whether SVZ stem and/or progenitor cells are motile in transgenic GFP+ slices with two photon time lapse microscopy and post hoc immunohistochemistry. We found that stem and progenitor cells; mGFAP-GFP+ cells, bright nestin-GFP+ cells and Mash1+ cells were stationary in the SVZ and rostral migratory stream (RMS). In our search for motile progenitor cells, we uncovered a population of motile betaIII-tubulin+ neuroblasts that expressed low levels of epidermal growth factor receptor (EGFr). This was intriguing since EGFr drives proliferation in the SVZ and affects migration in other systems. Thus we examined the potential role of EGFr in modulating SVZ migration. Interestingly, EGFr(low) neuroblasts moved slower and in more tortuous patterns than EGFr-negative neuroblasts. We next questioned whether EGFr stimulation affects SVZ cell migration by imaging Gad65-GFP+ neuroblasts in the presence of transforming growth factor alpha (TGF-alpha), an EGFr-selective agonist. Indeed, acute exposure to TGF-alpha decreased the percentage of motile cells by approximately 40%. CONCLUSIONS/SIGNIFICANCE:In summary, the present study directly shows that SVZ stem and progenitor cells are static, that EGFr is retained on some neuroblasts, and that EGFr stimulation negatively regulates migration. This result suggests an additional role for EGFr signaling in the SVZ.