National Institutes Of Health Training Research Articles

Hematopoietic stem cell-specific GFP-expressing transgenic mice generated by genetic excision of a pan-hematopoietic reporter gene.

Selective labeling of specific cell types by expression of green fluorescent protein (GFP) within the hematopoietic system would have great utility in identifying, localizing, and tracking different cell populations in flow cytometry, microscopy, lineage tracing, and transplantation assays. In this report, we describe the generation and characterization of a new transgenic mouse line with specific GFP labeling of all nucleated hematopoietic cells and platelets. This new "Vav-GFP" mouse line labels the vast majority of hematopoietic cells with GFP during both embryonic development and adulthood, with particularly high expression in hematopoietic stem and progenitor cells (HSPCs). With the exception of transient labeling of fetal endothelial cells, GFP expression is highly selective for hematopoietic cells and persists in donor-derived progeny after transplantation of HSPCs. Finally, we also demonstrate that the loxP-flanked reporter allows for specific GFP labeling of different hematopoietic cell subsets when crossed to various Cre reporter lines. By crossing Vav-GFP mice to Flk2-Cre mice, we obtained robust and highly selective GFP expression in hematopoietic stem cells (HSCs). These data describe a new mouse model capable of directing GFP labeling exclusively of hematopoietic cells or exclusively of HSCs.

Beyond Academia: Grad Students Offered New Tools to Find the Right Career

Less than one-quarter of students who receive PhDs in the sciences end up in the career for which they were trained—academic research. As part of a growing effort to better prepare graduate students and postdoctoral researchers for nonacademic jobs, the National Institutes of Health (NIH) created the Broadening Experiences in Scientific Training (BEST) program. In 2013 and 2014, BEST awarded nonrenewable 5-year grants of up to $250,000 a year to 17 universities. What emerges from BEST could be adapted by graduate schools in all disciplines, suggests Patricia Labosky, program leader in the NIH Office of the Director, who heads up BEST. BEST grew out of a 2012 report by a working group of the NIH Advisory Committee to the Director, concentrating on the biomedical research workforce. The goal is to broaden the view of what constitutes the scientific enterprise, explains Labosky. Faculty should encourage their trainees (grad students and postdocs) to explore any number of careers, whether as teachers, staff scientists for government or industry, entrepreneurs, policymakers, or science journalists. “All those things could end up benefiting the whole research enterprise in a huge way,” she says. Part of the challenge is changing a culture that views nonacademic jobs as “second class,” explains Ambika Mathur, dean of the graduate school at Wayne State University in Detroit, which was awarded a BEST grant. “The fact that NIH training grants have now changed the language to reflect the fact that these are considered successful careers is a huge victory,” she says. Mathur and colleagues wrote about BEST’s progress in an April 2015 article in Science Translational Medicine. At Wayne State, the BEST program is designed in three phases: In the first, students hear short presentations from panelists representing six career trajectories. In the second, the students can explore three of the six in daylong sessions. And in phase three, they pursue a summer internship in their preferred career path, with financial support from the university. Dan Feldman is a Wayne State grad student whose research is focused on nanoparticle engineering. He hopes to work for a biotech firm or other biological research company, such as Merck, where he had an internship. Through the BEST program, he says, “I was given the chance to network with local companies and different recruiters. I attended an industry-based panel and had a chance to meet with them.” He learned about marketing an idea and developing a business plan, skills he had not expected to learn as a scientist. He also expanded his resume to include opportunities he has been given to collaborate across disciplines and institutions. Those are the same skills that University of California, Davis, promotes through its BEST program, says Frederick J. Meyers, vice dean of the School of Medicine. Although UC Davis already had many careerbuilding initiatives, Meyers says, “The BEST grant brings together all these disparate resources in one coordinated portal for our grad students and post docs.” The portal offers modules in personal and career development, mentor resources, and online career guidance. Participants may receive a certificate that attests to their completing an NIHfunded program that prepares them in teambuilding, communication, and conflict management. UC Davis also expanded internship opportunities to include such careers as technology transfer, advocacy, and policymaking. “One way to change the culture of training is to allow young people to pursue their passions and not to feel like they have to say—but not really mean— that they want to go into academics,” says Meyers. “They can be honest.” At Michigan State University, selfanalysis and being “true to yourself ” is a key component of the BEST program, says Stephanie Watts, assistant dean of the Graduate School. In part because East Lansing has limited internship opportunities, Michigan State keeps its BEST cohort small, roughly 30 students a year. As with other BEST awardees, it will track its participants, comparing them with a non-BEST cohort over time. “We’re going to concentrate on doing this experiment very well,” says Watts. “The goal is to pull together a really good set of data.” The 17 BEST awardees meet periodically, both in person and through webinars, to share what is working and, as important, what is not. They discuss everything from creating a large internship bank to overcoming faculty resistance toward helping students find nonacademic career paths. “These trainees are not our employees,” stresses Mathur. “Our obligation is to provide them with the best career training opportunities.” NIH will share the best practices on its new website (www.nihbest.org) and through journal publications, among other avenues. Says Labosky: “I’m hoping that ten years from now, a competitive [graduate] program would need to have BEST-like activities, the sort of professional development activities that are a core part of what they’re doing,”

Biomedical Research: Strength from Diversity

The recent Education Forum by M. J. Graham and Colleagues (“Increasing persistence of college students in STEM,” 27 September, p. [1455][1]) called for widespread implementation of a much-needed framework for increasing persistence of college students in science, technology, engineering, and mathematics (STEM) fields. The Persistence Framework that they describe is evidence based, drawing from a rich body of research that has identified the relevant education and psychosocial issues that must be addressed, as well as effective strategies. Recognizing that the biomedical research enterprise would be greatly strengthened by attracting the most talented individuals from all groups, the National Institutes of Health (NIH) has been intensively engaged for more than 2 years in a planning process. As a result, a distinguished working group ([ 1 ][2]) has made a series of bold recommendations that are now in the process of being implemented. These include the systematic evaluation of NIH training programs, the appointment of a Chief Office for Scientific Workforce Diversity, and the launch of a new three-component program that will provide the resources necessary to implement and assess, on a large scale, approaches such as those described by Graham et al. Developing new ways to engage college students, sustain their interest in research, and provide trainees at all career stages with the strategies and tools to thrive in the biomedical research workforce are the goals of the “Enhancing the Diversity of the NIH-Funded Workforce” program ([ 2 ][3]). This program will consist of three highly integrated initiatives: 1. The National Research Mentoring Network (NRMN) will develop transformative approaches to mentoring. The network will engage diverse mentors from many biomedical research disciplines and link them to mentees at multiple career stages. 2. The Building Infrastructure Leading to Diversity (BUILD) initiative will support relatively under-resourced academic institutions with a demonstrated commitment to students from highly diverse backgrounds. These institutions will have the opportunity to develop a series of potentially transformative education and training activities that address the many factors underlying student/trainee persistence in biomedical research career paths and successful transition into the research workforce. BUILD emphasizes and requires the provision of research opportunities. The program will seek strength through collaboration across the spectrum of types of institutions. 3. The Coordination and Evaluation Center will work with both the BUILD consortium and NRMN to assess the efficacy of the various approaches that are being piloted. ![Figure][4] CREDIT: ANDREW TAYLOR/SHUTTERSTOCK History has revealed that addressing problems that disproportionately affect minority populations has often had a transformative impact for the majority as well ([ 3 ][5]). We predict that transformative approaches to student engagement and training developed through the Common Fund's Diversity Program will have a similar far-reaching impact on training everywhere. 1. [↵][6] NIH Advisory Committee to the Director, Diversity in the Biomedical Workforce Working Group Report (NIH, Bethesda, MD, 2012). 2. [↵][7] NIH, Enhancing the Diversity of the NIH-Funded Workforce ( ). 3. [↵][8] 1. M.N. Davidson , The End of Diversity as We Know It: Why Diversity Efforts Fail and How Leveraging Difference Can Succeed (Berrett-Koehler Publishers, San Francisco, 2011). [1]: http://www.sciencemag.org/content/341/6153/1455.full [2]: #ref-1 [3]: #ref-2 [4]: pending:yes [5]: #ref-3 [6]: #xref-ref-1-1 View reference 1 in text [7]: #xref-ref-2-1 View reference 2 in text [8]: #xref-ref-3-1 View reference 3 in text

“Recombinant protein of the day”: Using daily student presentations to add real‐world aspects to a biotechnology course

“Recombinant protein of the day”: Using daily student presentations to add real‐world aspects to a biotechnology course

Responsible Conduct of Research and Scholarship: Implications for Social Work Research

As number of students and faculty in schools of social work conducting research continues to increase, especially research funded by National Institutes of Health (NIH) and National Science Foundation (NSF), they have also had to pay greater attention to subject of responsible conduct of research and (RCRS). NIH and NSF mandate that undergraduate, graduate, and doctoral students, and postdoctoral fellows, receive training on RCRS. In this editorial, we provide a brief summary of history and nature of RCRS followed by examples of two differing RCRS training programs including a discussion of corresponding benefits and challenges. We conclude with recommendations for social work research and questions social work educators and researchers need to consider concerning RCRS education. RCRS refers to the practice of scientific and scholarly investigation with integrity. It involves awareness and application of established professional norms and ethical principles in performance of all activities related to scientific research and to scholarship (see http://www.scholarlyintegrity.umich.edu/guidelines/). Attention to subject of research integrity became a public issue in United States in 1981, when first congressional hearing was held on subject propelled by a series of allegations of misconduct (see http://ori.dhhs.gov/about/history.shtml. In fact, all aspects of research misconduct concerning NIH-funded research fall under authority of Department of Health and Human Services Office of Research Integrity (see http://ori.dhhs.gov/). As a result of this increased attention to research integrity, legislation has been passed to improve procedures by which applicants, institutions, and federal agencies prevent and address research misconduct. One of significant changes occurring since 1989 when NIH submitted first notice of policy related to instruction on research integrity (see http://grants.nih.gov/grants/guide/historical/ 1989_12_22_Vol_18_No_45.pdf) is that all trainees, fellows, participants, and scholars receiving any NIH support for training receive instruction in RCRS. Specifically, as stated in NIH's NOT-OD-10-019: NIH requires that all trainees, fellows, participants, and scholars receiving support through any NIH training, career development award (individual or institutional), research education grant, and dissertation research grant must receive instruction in responsible conduct of research. This policy will take effect with all new and renewal applications submitted on or after January 25, 2010, and for all continuation (Type 5) applications with deadlines on or after January 1, 2011. This Notice applies to following programs: D43, D71, F05, F30, F31, F32, F33, F34, F37, F38, K01, K02, K05, K07, K08, KU12, K18, K22, K23, K24, K25, K26, K30, K99/R00, KL1 KL2, R25, R36, T15, T32, T34, T35, T36, T37, T90/R90, TL1, TU2, and U2R. This policy also applies to any other NIH-funded programs supporting research training, career development, or research education that require instruction in responsible conduct of research as stated in relevant funding opportunity announcements (see http://grants1.nih.gov/grants/ guide/notice-files/NOT-OD-10-019.html) Core RCRS topics include following: * Data Acquisition, Management, Sharing, and Ownership * Conflict of Interest and Commitment * Protection of Human Beings Subjects * Research Misconduct, including Data Fabrication and Falsification * Personal, Professional, and Financial Conflicts of Interest and Commitment * Publication Practices and Responsible Authorship * Supervisory and Mentoring Relationships and Responsibilities * Responsibilities of Collaborative Research * Welfare of Laboratory Animals When Research Involves Human Participants and Animal Subjects It is important to comment here that preceding outline of topics clearly indicates that RCRS training encompasses a much broader and richer set of topics on RCRS than traditional training involving human subjects protection issues that researchers are quite familiar with. …

Patients, cells, and organelles: The intersection of science and serendipity

Patients, cells, and organelles: The intersection of science and serendipity

Dissociation of Neural Mechanisms Underlying Orientation Processing in Humans

Orientation selectivity is a fundamental, emergent property of neurons in early visual cortex, and the discovery of that property has dramatically shaped how we conceptualize visual processing. However, much remains unknown about the neural substrates of this basic building block of perception, and what is known primarily stems from animal physiology studies. To probe the neural concomitants of orientation processing in humans, we employed repetitive transcranial magnetic stimulation (rTMS), which can significantly attenuate neuronal spiking activity, hemodynamic responses, and local field potentials within a focused cortical region. Using rTMS to suppress neural responses evoked by stimuli falling within a local region of the visual field, we were able to dissociate two distinct components of the neural circuitry underlying orientation processing: selectivity and contextual effects. Orientation selectivity gauged by masking was unchanged by rTMS, whereas an otherwise robust orientation repulsion illusion was weakened after rTMS. This dissociation implies that orientation processing in humans relies on distinct mechanisms, only one of which was impacted by rTMS. These results are consistent with models positing that orientation selectivity is governed by patterns of convergence of thalamic afferents onto cortical neurons, with intracortical activity then shaping population responses amongst those cortical neurons.

Accelerating Research Productivity in Social Work Programs: Perspectives on NIH's Postdoctoral T32 Research Training Mechanism.

This article describes the experiences of four social work researchers who pursued an alternative career path immediately following their doctorate in social work by accepting a postdoctoral training fellowship funded by the National Institutes of Health (NIH). As schools of social work look for creative ways to build research capacity, this article describes the authors' perspectives regarding the considerations to accept postdocs, key elements in their training programs, lessons learned, and outcomes from training. To provide an overview of the funding mechanism and distribution of funds to institutes and centers relevant to social work, data were obtained from databases that list NIH training grants awarded each year. Study results showed a limited amount of variation in fellows' training plans. The majority of training time was spent building skill in manuscript preparation, grant development, and socialization to the NIH culture. Above all other themes, the desire for advanced research training was a critically important factor in accepting a postdoctoral training position. Finally, the outcomes of training may have a profound effect on professional development, yet the long-term trajectory of postdoctoral fellows in academic positions as compared with people without postdoctoral training in social work programs requires further study.

Reported Goals for Knowledge to Be Learned in Responsible Conduct of Research Courses

EDUCATION IN RESPONSIBLE CONDUCT OF RESEARCH (RCR) has been a required part of training for students on U. S. National Institutes of Health (NIH) training grants for over 15 years. However, there is little evidence of commonly accepted goals for RCR instruction, making it difficult to assess effectiveness. As part of a larger study examining RCR instructors' goals for RCR education, this report focuses on those reported goals categorized as knowledge. To identify RCR instructors, e-mail requests were sent to the 116 recipients of NIH training grants awarded in 2000. Of 67 verified RCR instructors, 50 (75% response rate) from 37 different institutions were successfully interviewed. Despite a shared sense of the basics to be taught in RCR courses, these instructors were diverse in their views and understanding of goals for RCR education. This diversity suggests a challenge to be overcome not only for improving the effectiveness of RCR education, but also for attempts to assess that effectiveness.

Symbiosis: Chemical Biology at Wisconsin

C hemical biology has been percolating at the University of Wisconsin (UW)–Madison for most of the university’s history (www.chemicalbiology. wisc.edu; 1–4). UW–Madison played a predominant role in early research on vitamins—those small molecules that are essential in trace amounts for human life. There, Harry Steenbock developed the irradiation process for the production of vitamin D and thereby eliminated the scourge of rickets (5, 6). Vitamin A was discovered at Wisconsin, as were the vitamin B complex and the hormonal form of vitamin D. Karl Paul Link isolated the potent anticoagulant dicoumarol there and then synthesized warfarin, an analogue that is still a common chemotherapeutic agent. Microbial fermentation methods developed at UW–Madison enabled the large-scale biosynthesis of penicillin and other antibiotics. H. Gobind Khorana carried out the first chemical synthesis of a gene there (7), andW. S. Johnson and Eugene van Tamelen devised synthetic routes to steroids inspired by the biosynthesis of this critical class of natural products (8). The use of natural protease inhibitors to devise highly effective inhibitors of aspartyl proteases was an insight that arose atWisconsin andwas used to design potent HIV protease inhibitors (9). These and other triumphs demonstrate an early symbiosis of chemistry and biology, which fostered the training of eminent interdisciplinary scientists such as Carl Djerassi and Ralph Hirschmann. Seeking to coalesce the well-established success in research at the interface between chemistry and biology, Dan Rich sought one of the initial Chemistry–Biology Interface (CBI) Training Grants from the National Institutes of Health (NIH) in 1993. His vision was to provide graduate students with a multitude of opportunities for interdisciplinary training in chemistry and biology. The process of preparing the grant application launched the UW–Madison program in chemical biology (www.chemical biology.wisc.edu). The now long-standing NIH training grant remains a core component of graduate training in chemical biology at the university. Since the inception of the training program, UW–Madison’s commitment to graduate-student training in chemical biology has increased. For example, the university has made the recruitment of faculty members with research interests in chemical biology a priority. As a result, graduate students have a wide variety of research options from which to choose. In addition, a powerful infrastructure for conducting chemical biology research has been built. Third, courses in chemical biology have been developed that employ innovative teaching methods. These courses are designed not only to introduce students to concepts in chemical biology but also to build their skills in critical thinking, creative problem selection, and communication. Lastly, students affiliated with *Corresponding author, kiessling@chem.wisc.edu.

National Institutes of Health (NIH) activities concerning nutrition research related to food composition databases

Approximately 4% of the research expenditures for the US National Institutes of Health (NIH) is used to support nutrition research and training within NIH laboratories (intramural program) and in research institutions in the US and abroad (extramural program). In fiscal year (FY) 2000, the funding for NIH nutrition research and training was $694.9 million for 3150 projects. The research areas are broad and include the functions of nutrients and other food components in biological systems, the dietary intakes needed to prevent disease and/or promote optimal health, variables that affect nutrient functions and requirements, and genetic differences in needs and responses. The results of the many nutrition research projects and programs may help the Agriculture Research Service (ARS) of the US Department of Agriculture (USDA) establish priorities for analyzing food components and including them in USDA food composition databases. NIH research projects are described and tracked through the Human Nutrition Research Information Management (HNRIM) system. A recent search for the key word antioxidants, food components of great interest to database developers and users, identified 131 projects, many with direct relevance to specific foods. NIH, along with other government agencies, provides financial support for the ARS, USDA National Food and Nutrient Analysis Program (NFNAP), which began in 1997. NIH support for NFNAP amounted to $1 850 000 in FY 2001. NIH is currently providing support for four NFNAP complementary databases: Native American foods, USDA commodity foods, choline, and fluoride. NIH provides support for segments of the National Health and Nutrition Examination Survey (NHANES) conducted by the National Center for Health Statistics (NCHS). NIH support for NHANES was about $5.3 million in FY 2001 (about 12.4% of FY 2001 costs for the survey), and discussions are underway to assure continued NIH support for this survey.

The NIH Stroke Scale is unreliable in untrained hands

Background and Purpose: The NIH (National Institutes of Health) Stroke Scale helps to define candidates for thrombolytic treatment and other important clinical decisions. We evaluated its use by last-year medical students who had no specific training in use of this scale. Methods: The scale (principles, utilization, methods for scoring, main pitfalls) was presented between 2 stroke lectures. Following a 30-minute study period, a case from the NIH training videotape (case 1, tape 2, total score 4) was presented, and the 13 items were scored by 42 voluntary students. The analysis focused on possible errors of potential clinical relevance. Results: Only 15 students (36%) scored all items correctly. Twenty (48%) gave results at least 2 points apart from the correct total score, and 14 students had scores ≥6, which could lead to the inappropriate use of recombinant tissue-type plasminogen activator (rt-PA). At least 10% of the students made mistakes in most (8 of 13) items of the scale. Conclusions: Graduating medical students are not ready to use the NIH Stroke Scale without specific training. The magnitude of the mistakes found in this study is enough to inappropriately include or exclude patients from rt-PA treatment. Training programs should be considered a sine qua non for qualification for rt-PA use in daily clinical practice. Copyright © 2002 by National Stroke Association

Graduate education in the biomedical sciences

Several aspects of the processes for the pre- and postdoctoral training of PhDs and the postdoctoral research training of MDs are critically examined. The size of the predoctoral pipeline, the sources of support for the students in it, trends in the annual production of bioscience PhDs, and prospects for growth in opportunities, as defined in increases in availability of public and private funds for research, are catalogued. Evidence for the existence of a surplus of research scientists--based on the size and growth of the pool of postdoctorals, the success rates now being experienced by young postdoctorals in competing for National Institutes of Health (NIH) grants, and the success of young postdoctorals in securing career employment--is evaluated, and the conclusion that the nation is producing too many research scientists is suggested. The pros and cons of "downregulating" the production of scientists are explored, the difficulties of reaching a national consensus on the degree of reduction and the partition of reduction among fields of science and academic institutions and academic departments are described, and the mechanisms conceivably available for accomplishing the task--reducing NIH training funds, autoregulation by academic institutions and/or scientific disciplines, and reliance on the decisions of well-informed (probably by the National Academy of Sciences) degree candidates--are enumerated; a preference for the last of these mechanisms is indicated. The NIH's formal training programs are compared with its informal support of training under research grants; questions that the latter practice raises are identified. The striking disparity between the duration of training for conventional predoctoral PhD candidates and that for dual-degree (MD-PhD) aspirants is noted. The measurement problems of assessing the duration of postdoctoral training are highlighted. The fact that dual-degree scientists seem to compete little, if any, more successfully for the great bulk of NIH research grants than do singly-degreed MDs or PhDs is noted, suggesting the advisability of a fresh and objective review of these dual-degree programs, especially the NIH's Medical Scientist Training Program, to reassess their value in the light of their cost. Some characteristics of careers in the biomedical sciences are outlined. Data are presented on the high turnover rates of first-time-ever entrants into the pool of NIH grantees or, stated otherwise, the relatively low rates of survival of principal investigators (PIs) in the NIH research grant system; a method of estimating the steady-state number of NIH ex- PIs "around" at any given moment is proposed.(ABSTRACT TRUNCATED AT 400 WORDS)