Broader Impacts

SHARING MCB SCIENCE: EVIDENCE FOR AUTOPHAGY-DEPENDENT PATHWAYS OF RIBOSOMAL RNA TURNOVER IN ARABIDOPSIS

Ribosomes play an essential role in protein manufacturing in the cell, and are made up of ribosomal RNA (rRNA) and proteins. While scientists understand a great deal about how ribosomes are created, surprisingly little is known about how they are broken down at the end of their useful life. Understanding ribosome turnover is important, because each cell invests a lot of energy and resources to maintain a sufficient number of ribosomes to keep up with its protein production demands.

As described in a recent publication in the journal Autophagy, a collaboration between Iowa State University’s Loomis Professor of Plant Physiology Dr. Diane Bassham, Associate Professor of Biochemistry Dr. Gustavo MacIntosh, and their research groups resulted in the discovery that eukaryotic cells may be using a process called autophagy to break down ribosomes. In autophagy, a compartment (called an autophagosome) is created by autophagy-related proteins (ATGs) around the cargo slated for destruction, and the autophagosome with its cargo is trafficked from the cytoplasm of the cell to an organelle called a vacuole (in plant cells) or a lysosome (in animal cells). Fusion with the vacuole or lysosome results in the cargo being deposited inside the organelle with the enzymes required for its destruction. One such enzyme, called RNS2, is from the RNase T2 family of ribonucleases (enzymes that break down RNA into smaller components).

Hypothesizing that the process of autophagy may play a role in breakdown of ribosomes, the research team developed a method to measure ribosomal RNA accumulation in the vacuole of mutant plant (Arabidopsis thaliana) cells lacking the RNS2 ribonuclease. The mutant is called rns2-2. The researchers used confocal microscopy to look for evidence of autophagy activation and the accumulation of autophagosomes. Fluorescent labeling of an ATG protein on the surface of autophagosomes provided evidence of an increased number of autophagosomes (indicated by small, fluorescent blue dots in the image) in the rns2-2 mutant when compared to normal, wild type (WT) Arabidopsis thaliana plant cells. Bassham DataThis result allowed the research team to further hypothesize that autophagy activation in the rns2-2 mutant was compensation for the plant cells’ inability to degrade rRNA with the vacuolar ribonuclease RNS2.

The research team also found evidence of the involvement of more than one autophagy pathway in the breakdown of ribosomes. As described in their publication, mutations in an autophagy gene (ATG5) blocked the activity of the autophagy pathway and prevented accumulation of rRNA in the vacuole. But, mutations in a different autophagy gene (ATG9), did not prevent accumulation of the rRNA in the vacuole, suggesting the pathway used by ATG5 and ATG9 to deliver rRNA to the vacuole may be different. As Dr. Bassham notes, “Our results shed light on the mechanisms by which ribosomal components are recycled and in turn, on the way in which ribosome number and quality are controlled.”  Dr. Bassham credits NSF MCB support to “allow Dr. Gustavo MacIntosh and I to reinforce and expand our collaboration by establishing a group consisting of a post-doctoral researcher, several graduate students, and undergraduate students to work together in the analysis of the relationship between autophagy and RNA degradation, allowing progress that would have not been possible had our research groups continued to work independently.”

When asked about the broader impacts of her research, Dr. Bassham responded:

“A major impact of our project has been training students in research. In addition to training several graduate students and a post-doc who worked full time on the research project, ten undergraduate students participated in laboratory research in our summer internship program, including several from the primarily undergraduate institution Grand View University in Des Moines, IA, who would otherwise not have the opportunity to gain research experience. A second outcome is the continued development, headed by Iowa State University Professor Eve Wurtele, of an educational video game called Meta!Blast that is used to teach cell biology to undergraduate and high school students. In the game, the player navigates a three-dimensional cellular environment within a plant and completes tasks based on cell functions and biochemical reactions. Interactivity aids retention and understanding of concepts and the use of multimedia allows us to reach diverse populations of students. The process of autophagy was incorporated into the game as a result of this project.”

This work is funded by the Division of Molecular and Cellular Biosciences, Award #MCB-1051818.

The National Alliance for Broader Impacts

The Broader Impacts Merit Review criterion (BI) plays a crucial role in NSF’s mission. BI activities advance scientific knowledge and contribute to socially relevant outcomes. The basics of Broader Impacts were addressed in an infographic we previously shared on the blog.

If you have submitted a proposal to the NSF, you are aware that the BI activities of a project are part of the Foundation’s Merit Review process. But… what are Broader Impacts activities? The term “broader impacts” has wide-ranging implications, thus there are many questions about this subject in our scientific community.

MCB is excited about the first, of what we hope to be many, posts featuring the BI activities of MCB-funded investigators. We hope to share a sampling of projects that represents the diversity of activities and their outcomes. If you are: 1) an MCB-funded researcher and 2) would like to share your research and broader impacts activities, please fill out this form to be considered for a future post.

The National Alliance for Broader Impacts (NABI) is a national network of individuals from universities, professional societies, and science organizations that focuses on promoting Broader Impacts activities locally, nationally, and internationally (NSF award #MCB-1313197). NABI is committed to creating a community of practice by achieving the following four objectives:

  • identify and curate promising models, practices, and evaluation methods for the BI community;
  • expand engagement in and support the development of high-quality BI activities by educating current and future faculty and researchers on effective BI practices;
  • develop the human resources necessary for sustained growth and increased diversity of the BI community; and
  • promote cross-institutional collaboration on and dissemination of BI programs, practices, models, materials, and resources.

An important aspect of NABI’s mission is to provide professional development and support for researchers. To do so, offices have been created at many institutions to help researchers design, implement, and evaluate their BI activities. A great example of this effort is the Broader Impacts Network at the University of Missouri (NSF award #MCB-1408736).

NABI also coordinates the annual Broader Impacts Summit (award #IIA-1437105). The summit is a great platform to discuss issues related to BI, to cultivate new ideas, and move the field of BI forward. The summit also presents a unique professional-development opportunity for BI support staff.

When asked about the future of NABI, Dr. Susan D. Renoe, adjunct professor of anthropology at the University of Missouri and director of the Broader Impacts Network, responded:

We will continue to provide high-quality professional development for individuals and broader impacts support for researchers through our programming. In addition, the future of NABI represents the future of broader impacts. As our network grows, so, too, will the scope and scale of the broader impacts of research.”

Award #MCB-1408736 is co-funded by the Division of Molecular and Cellular Biosciences and Emerging Frontiers in the Directorate for Biological Sciences and by the Division of Chemistry in the Directorate for Mathematics and Physical Sciences.

MCB Bids Farewell to the Summer 2015 Interns

This summer, the Division of Molecular and Cellular Biosciences had the pleasure of hosting three summer interns. These outstanding undergraduate students culled through proposals, awards and annual reports to identify trends related to informal science education, minority involvement in broader impacts, and the impact of statistical and quantitative analyses on MCB-funded projects. The preliminary data produced by the interns generated several follow-up questions to be explored in the future.

Anita AlbanFullSizeRenderese, a rising senior at the University of Nevada, Reno, investigated informal science education in  active awards in the division. With the help of her mentors, she created a working definition of informal science education as any educational activity the PI participates in outside of the required curricula. These activities included training graduate and undergraduate students, K-12 outreach, lectures or blog posts targeted toward the public, and creating workshops and conferences. In addition to investigating the types of informal education, Anita also considered the length of time that principal investigators were funded, as well as their institutional resources. The division will use these data to continue to investigate what environments influence successful informal science education activities.

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Melissa Sam, a rising junior at Northeastern State University used her love of math and statistics to learn more about the use of Big Data analyses in MCB-funded projects. Melissa included the use of both statistical methods, such as the Markov Model, network analysis, bioinformatics, and principal component analysis, and quantitative methods, such as mass spectrometry, NMR spectroscopy, ChIP-sequencing, and next generation sequencing, to define “Big Data Analyses” for her research this summer. She investigated the number of different statistical or quantitative methods per proposal, the costs associated with employing these methods, as well as the impact on the scientific community ( ie. papers, presentations, and book chapters).  Her research findings will be useful to the division whose priorities for research support include quantitative and predictive cell and molecular biology.

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Mikah Barrueta,a rising senior at Otternbein University, spent her summer investigating minority involvement in the broader impacts of MCB-funded research by comparing promises to include underrepresented groups in proposals to reported outcomes in annual reports for a representative sample of awards. In addition, Mikah surveyed program directors and principal investigators to learn more about how the involvement of underrepresented groups is reported to NSF. She evaluated several topics including ways to improve reporting to better capture the demographics of participants in broader impact activities. Mikah’s data and analysis will be considered by the division, as it conducts follow-up research to address questions which emerged as a result of her research.

iBiology: Sharing Research One Video At a Time

The growth in interdisciplinary science over the past decade has led to new developments in biological knowledge and techniques. For example,  CRISPR technology allows scientists to make specific changes to genomes and has transformed the field of genetics. As the field of biology increases in complexity due to technological innovations and expansion of knowledge, new ways to teach and communicate science must be developed. iBiology addresses this challenge by sharing science in the form of easy-to-watch video seminars,  and aims to lead the way in creating ways to spread interest in science for educational and scientific communities.

One of the main goals of iBiology is to bring research questions currently being explored by top-level scientists to students, scientists, and educators. This is most visible in the recently launched video series, “Great Questions in Life Sciences.” Investigators reveal the great scientific problems at the intersection of physics, computation, and biology that will demand attention over the coming decade. These videos offer the viewer a unique glimpse into the forefront of research and are intended to spark the curiosity of young scientists and students considering a career in life sciences research.

In talking to iBiology’s Associate Director, Dr. Shannon Behrman, we learned that, not only does iBiology want to expose the biological questions that are being actively pursued; they also hope to demystify what it would be like to become a researcher in various fields of biology answering those very questions.  Videos under the “How I Became a Scientist” section show interviews with various well-known scientists outlining their journeys to becoming researchers. Other videos under the “Careers” section show different career paths that are open to someone with a science degree. Each of these videos help to make this broad field more accessible by providing professional advice to aspiring students.  This early exposure to research helps young scientists feel like they can fit into and make a difference in the scientific community.

iBiology does not just provide a tool for students to see what current leaders in the field of biology are working on. They also provide a much-needed teaching resource. The program provides a plethora of educational resources and study tools for students in several different fields of biology, including biochemistry, genetics, microbiology, and human health. To support science teachers, iBiology provides possible questions for various assessments for students, along with a key terms index to help shape their curriculum.

For science to thrive, it needs innovative ideas.  iBiology answers this call with new approaches for getting students to become more interested in science, and by providing these students with resources to help them succeed in their scientific endeavors.  As a result, the iBiology team hopes to see more young people bringing in new and innovative approaches to current research problems in the future.

Cecilia McIntosh Recognized for Research and Mentoring

Dr. Cecilia McIntosh has studied the structure and function of secondary metabolites in fruit for over 20 years at East Tennessee State University (ETSU). She has had the opportunity to mentor and train over 60 students in her role as a professor of biological science and now, as Dean of the School of Graduate Studies. This year, Dr. McIntosh’s commitment to scientific education and outreach has been recognized by various organizations at ETSU and in the surrounding communities.  The Bristol YWCA has selected McIntosh to receive one of twelve Tribute to Women Awards this year. This annual award program recognizes the outstanding achievements of individuals throughout East Tennessee and Southwest Virgina. Recipients are nominated by area organizations and selected to represent the arts, education, business, and community efforts. In addition to being recognized by her larger community, Dr. McIntosh has been named a 2015 Notable Woman of ETSU and selected to receive the 2015 ETSU College of Arts and Sciences Outstanding Faculty Research Award.  Dr. McIntosh credits NSF support as a significant factor in her ability to have a productive research career.  Congratulations to Dr. McIntosh for her achievements!

Dr. Brian Hoffman selected as a fellow for the International EPR (ESR) Society

The International Electron Paramagnetic Resonance (Electron Spin Resonance) Society has announced  Brian Hoffman  as a 2015 Fellow.   The Hoffman research group at Northwestern University studies electron transfer and resonance in proteins and metalloenzymes using a combination of nuclear magnetic resonance (NMR) and electron spin resonance (ESR) techniques.  This interdisciplinary approach to understanding the fundamental processes through which protein-protein interactions occur has made significant strides in the field, evidenced by a robust publication record and over two decades of research funding from the Division of Molecular and Cellular Biosciences.  Congratulations, Dr. Brian Hoffman!

Making the Leap From RUI to Graduate Research Fellowship

In 2013, Emina Stojkovic, Associate Professor at Northeastern Illinois University was awarded a Research in Undergraduate Institutions (RUI) grant from MCB to study light-responsive proteins in the development of myxobacteria. The RUI award mechanism is designed to support faculty at predominately undergraduate institutions conducting research that engages them in their professional field, builds capacity for research at their home institution, and supports the integration of research and undergraduate education.

We are excited to report that Dr. Stojkovic’s research, mentoring, and advising activities at the undergraduate level have resulted in four students being awarded National Science Foundation Graduate Research Fellowships to support their graduate studies. Two of the students, Angela Varela and Anna Baker, were undergraduate researchers trained in Stojkovic’s laboratory by working on the RUI project. The other two students, Daniel Westcott and Christopher Craddock were trained in research groups that collaborated with Stojkovic on interdisciplinary projects.  The students share more about their research interests in this press release provided by Northeastern Illinois University. In response to this news Dr. Stojkovic states, “The impact that NSF has had on our alumni and the students who are on their way to graduate from our department is tremendous. I am honored and grateful to serve in the role of a mentor and primary investigator.”

Jennifer Doudna featured as Influential Scientist in Time Magazine

Time Magazine recently published the “Time 100“, a list of influential leaders in their respective fields. We are pleased to report that MCB-funded investigator Jennifer Doudna was included as an influential scientist for her transformative research to develop gene editing technology.

Dr. Doudna , along with colleagues and collaborators, developed a now widely used genome editing tool known as the CRISPR-Cas1 system.  This invention emerged from Dr. Doudna’s interest in learning how an apparent bacterial adaptive immune system functions on a molecular level that is capable of protecting bacteria from deleterious foreign nucleic acids, including those delivered by bacteriophages. She and others found that CRISPR sequences represent a form of “memory” resulting from previous exposure to foreign DNAs and showed that fragments of these exogenous DNAs are integrated into the CRISPR array. Upon phage invasion, the CRISPR sequence is transcribed, together with a down-stream cas gene that encodes an endonuclease, such as Cas9 in Streptococcus pyogenes. The long, non-coding pre-CRISPR RNA (pre-crRNA) transcript is then processed, producing multiple different crRNAs. The crRNAs form a hybrid to a second CRISPR-encoded RNA called transactivating CRISPR RNA (tracrRNA), which has regions of complementarity to the various crRNAs. These RNA hybrid oligomers associate with the endonuclease and serve as a guide to target newly invading nucleic acids. Recognition of the foreign DNA triggers precise double-stranded cleavage, leading to complete nucleolytic degradation.

Understanding the molecular events by which CRISPRs function on the molecular level led Dr. Doudna and her collaborators to develop the pioneering genome editing capability that functions broadly across many species. Dr. Doudna gives an overview of this technology in the following video.

NSF funding for Dr. Doudna’s groundbreaking research began in 2007 and continues today.  Her research represents an excellent example of how fundamental research inspires innovation.

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1CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. These repeats are often associated with coding sequences for RNA-guided DNA endonuclease enzymes, general denoted “Cas” for CRISPR-associated.

Working Towards Gender Equity in Science

Broader impacts associated with NSF grants come in all forms and address issues such as:

  • public understanding of the science NSF funds
  • engaging the next generation of elementary school children in science to nurture the excitement of our future generation of science leaders
  • bringing computational science education to the biological sciences at the undergraduate level to ensure that the newest biologists to enter the field can succeed at the quantitative, predictive, theory driven cell and molecular biological sciences that NSF supports.

This week, the Editors share an example of Broader Impacts from a researcher supported by MCB that addresses the issue of unconscious bias and gender equity in science.

As part of her broader impacts, Dr. Karen Fleming, professor of Biophysics at Johns Hopkins University, is hosting a series of professional workshops focusing on gender equity in science. The goal of these workshops is to empower women in the STEM fields with tools for success. The workshops do this by facilitating a dialogue between graduate students, postdoctoral students and faculty members on diversity topics highlighted by readings from the social psychology literature. Topics covered to date include: unconscious bias, the confidence gap, and emotion in the workplace.

In her first workshop, Dr. Fleming discussed Jo Handelsman’s 2011 PNAS paper entitled “Science faculty’s subtle gender biases favor male students.” This paper investigated women and men faculty’s response to hiring a male or female for a laboratory manager position based on the exact same application except the first name was either John or Jennifer. One extraordinary finding from this paper that contradicts what many would expect is that both men and women faculty discriminated against the female applicant. The reason for this observation is thought to be unconscious bias, which has been another subject of one of Dr. Fleming’s workshops. Prior to this meeting, attendees were encouraged to measure their own unconscious biases using online modules put forth by Project Implicit. Another key finding from the literature that was discussed this year included the confidence gap. Systematic confidence differences between men and women are documented – women exhibit a tendency to underrate themselves, while men overrate themselves. This confidence gap becomes detrimental to a woman’s career when it hinders her ability to take action in the workplace. The most recent workshop considered the topic of emotion in the workplace. This is not viewed equally for both genders: studies have shown that men and women displaying emotion in the workplace are rewarded and penalized, respectively.

After a brief review of the findings of each journal article, the studies are discussed in-depth along with the applications of the findings to the social context of academia. Although current graduate students have raised concerns about the future of equity in the academic science workplace, tenured faculty have noted the leaps towards gender equity that have occurred in the past decades. Discussions have concluded that fostering an attitude of awareness, openness, and accountability of both men and women in science will aid in achieving gender equity in science. Before these workshops were available at JHU, there were few opportunities to regularly discuss these issues because neither unconscious bias nor gender equity training is mandatory in the sciences at many universities, JHU included.

Future seminars in the 2015 academic calendar include a panel of tenured women faculty in various science departments who will answer questions and comment on their experiences with gender equity in science. Further reading and links to the primary literature mentioned above can be found on Dr. Karen Fleming’s blog on achieving gender equity in science.

Do you have a great example of broader impacts that you would like to share? Please email the editors at mcbnews@nsf.gov or write to us using a feedback form.