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MCB AT YOUR MEETING: GENETIC CODE EXPANSION WORKSHOP

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A unique workshop for researchers interested in using emerging technologies in synthetic and chemical biology to create proteins with non-canonical amino acids (unnatural proteins) will be offered July 31 – August 5, 2017 by Dr. Ryan Mehl, Director of the Unnatural Protein Facility at Oregon State University. As part of the broader impacts of research supported by the Molecular Biophysics cluster of the Division of Molecular and Cellular Biosciences (#MCB – 1518265), Dr. Mehl created a week-long Genetic Code Expansion (GCE) workshop. Combining lectures, such as “GCE: When things don’t work, ‘the good, the bad, the ugly,’” with hands-on training in GCE techniques in the lab, workshop attendees will receive the best of what the Unnatural Protein Facility resource provides researchers year-round. Dr. Mehl is experienced in using the technology in his own research to design unnatural proteins and in training collaborators for more than ten years.

The workshop is the ideal opportunity for those who want to learn GCE techniques, are having trouble succeeding with GCE, want up-to-date theoretical and practical knowledge about GCE, or are curious about GCE and want to start out on the right foot when using unnatural proteins in their own research. The interactive format of the workshop not only provides technical know-how, but also allows researchers to learn from each other’s successes and failures, spark ideas, and foster relationships that can develop into collaborations.

To get the most out of the experience, a background in biochemistry and a working knowledge of protein expression techniques are necessary. The workshop is designed for professors, post-doctoral researchers, and graduate students, although advanced undergraduate students have previously attended. Participation is limited and spaces are going fast, so if you are interested, apply today. Registration fees increase after July 1. For more details, including how to apply, visit the website here.

Broadening the Impact of Science

Broader Impacts (BIs) are the contributions to society and advancement of scientific knowledge that result from research. As we previously noted on the MCB blog in this infographic, there are many different ways science can have broader impacts. The BI activities and outcomes spotlighted in this post were submitted by MCB-funded researchers as examples of what they have accomplished with MCB support, not prescriptions for success during the merit review process. If you are: 1) an MCB-funded researcher and 2) would like to share your broader impacts activities with our readers, please fill out this form to be considered in a future post.

The top image shows the Slideboard website homepage which contains pictures of cells tagged with fluorescent markers in green and orange and text that says “Welcome to Slideboards – Explore Slideboards – Learn More.”The bottom image shows an example slideboard. On the bottom left of the slideboard example is a white screen shot of the title “Localization and abundance analysis of human IncRNAs at single cell and single molecule resolution,” authors “Cabili MN*#, Dunagin MC*, McClanahan PD, Biaesch A, Padovan-Merhar O, Regev A*, Rinn JL*#, Raj A*#; *equal contributions, #corresponding authors,” and the reference “Genome Biology 2015, doi:10.1186/s13059-015-0586-4,” followed by the acknowledgement “Great work led by Moran Cabili and Margaret Dunagin. A wonderful collaboration between the Rinn, Regev, and Raj labs!” On the bottom right of the slideboard example is a repeat of the title and author list, a dropdown arrow, twitter symbol, Facebook symbol, and a list of questions with hyperlinks to answers created by the students who made the Slideboard. The questions ask “1. Where can I learn more about IncRNA? 2. How did we choose the IncRNA to screen? 3. Did you test whether any types of stress change localization or abundance? 4. Should I do a two-color validation of my IncRNA FISH? 5. Was there any correlation between whether a probe “failed” and any other factor from RNA-seq? 6. What are these off targets that create the non-specific background? 7. What sorts of inconsistencies did the two color assay reveal? 8. Were these patterns the same across cell types?”

Slideboard website homepage (top) and an example slideboard with title page and Q & A (bottom), which are available at http://slideboard.herokuapp.com/.

Once a scientist makes a discovery, it is off to the presses to publish. The resulting journal article can be lengthy and filled with jargon, because it serves as a how-to guide for other scientists in the field to repeat experiments. Though very informative to experts, scientific publications can be challenging for students and the general public to read quickly and understand. Dr. Arjun Raj, MCB CAREER recipient and Associate Professor of Bioengineering at the University of Pennsylvania, and his research team came up with a new way to communicate science called “Slideboards.” As shown at the bottom of the image, slideboards contain the title, citation, and authors of journal articles, followed by lists of frequently-asked questions with in-line answers. Teams of graduate and high-school students generate each slideboard by asking and answering their own questions about the paper. Online readers can use a form at the bottom of the slideboard to submit their own questions, which are answered by the students. Creating a slideboard allows the team to practice using web-based technology, and translating complex scientific literature into a summarized question-based format. This outreach project also helped graduate students develop skills necessary to present their own research, while encouraging high-school students to learn about scientific projects at the leading edge of the field. To view the Slideboard website, go to http://slideboard.herokuapp.com/.

This work is partially funded by the Cellular Dynamics and Function Cluster of the Division of Molecular and Cellular Biosciences, Awards #MCB – 1350601.

A group of students and graduate student Laura Bankers stand on a bridge over water in front of trees and grass on a nature hike at the Science Booster Club’s 2016 evolution summer camp (top left). Graduate student Kyle McElroy talks with a group of students in front of trees and grass by water during the 2016 evolution summer camp. He is gesturing with his hand, and wearing a green shirt and orange and black ball cap. One of the students, a young girl is smiling wearing a checkered blouse and green lanyard (middle left). A group of young men who are seated in a classroom at a table smile at the camera and hold up vials of DNA that they learned how to extract during the 2016 evolution summer camp while wearing a blue and orange tee-shirt, grey tee-shirt, blue tee-shirt and blue and white ball cap, or a black tee-shirt. Two are wearing orange lanyards around their neck and one is wearing purple lab gloves. In the background other youth participants are standing in front of a monitor glowing on the wall. (bottom left). Dr. Emily Schoerning is dressed up as Captain Planet in a green wig, red shirt and shorts, and blue nylons. She is standing with her arms up in a superhero pose in front of a window near potted plants (top right). Undergraduate student Jorge Moreno, wearing a black polo shirt and jeans with a yellow badge, and graduate student Laura Bankers in a grey dress. Both are standing in front of a yellow and black wall with a display monitor, and are standing behind a table with candy, flyers, and other materials, talking to off-screen participants (bottom right).

Attendees at the Science Booster Club’s 2016 evolution summer camp enjoyed nature hikes with graduate student Laura Bankers (top left), discussions of the evolution of parasites with graduate student Kyle McElroy (middle left), and gained hands-on experience extracting DNA with Integrated DNA Technologies (bottom left). The Science Booster Club hosted visits with Dr. Emily Schoerning as Captain Planet (top right), and discussions with undergraduate Jorge Moreno and graduate student Laura Bankers at the Iowa State Fair (bottom right).

As you look around the sidelines at a sporting event, you may notice a group of parents enthusiastically raising funds for new team uniforms or sporting equipment (booster club). Taking that concept out of the world of sports and into the world of science, Dr. Maurine Neiman (Associate Professor of Biology at the University of Iowa) and Dr. Emily Schoerning (Director of Research and Community Organizing at the National Center for Science Education) teamed up with students at the University of Iowa to create a Science Booster Club. The Science Booster Club held a summer camp (images on the left) and participated in community-organized events such as the Iowa State Fair (images on the right). At each event, club members facilitated fun, interactive science activities and discussions with the public. The group also raised funds to purchase and donate equipment to local science teachers. Young people attending these events, often from underserved areas that lacked scientific resources, have the chance to see themselves as scientists by learning through a hands-on approach. Graduate and undergraduate booster club members also gained valuable grant writing and proposal review, outreach, communication, education, and event planning experience – skills that are useful in future professional scientific careers. As such, for his work in the science booster club, graduate student Kyle McElroy received a 2017 summer stipend from MCB’s NSF 16-067 supplement to improve graduate student preparedness for entering the workforce. Dr. Schoerning noted, “We worked with over 54,000 Iowans last year during this pilot project at the University of Iowa, and have expanded into a national program in 11 states.” Click here to learn more about the Science Booster Club at the University of Iowa.

This work is partially funded by the Genetic Mechanisms Cluster of the Division of Molecular and Cellular Biosciences, Awards #MCB – 1122176.

Spotlight on MCB-funded Science

 

A spotlight illuminates the words 'Spotlight on MCB-funded Science.'

Photo Credit: Matusciac Alexandru/Shutterstock.com

Sharing MCB Science is one of our six blog themes where you can learn about exciting MCB-funded research submitted by our investigators (via this webform). We greatly appreciate the overwhelmingly positive response of the MCB scientific community and have received many more submissions than can be featured in long form on the blog. Enjoy this shorter spotlight of submissions we have received!

Ever wonder how a cell makes a tough decision? When food is scarce, Bacillus subtilis (a common soil bacteria) faces a difficult choice of when to shut down cellular processes and become dormant via sporulation (spore formation). Timing is key: wait too long and die from starvation; sporulate too early and die from crowding by rapidly dividing neighboring bacteria. What serves as the trigger – a specific biochemical signal or a more general physiological response – to enable starvation sensing and sporulation was unknown. As part of a collaborative project, Dr. Oleg Igoshin, an Associate Professor in the Department of Bioengineering at Rice University, Dr. Masaya Fujita, an Associate Professor in the Department of Biology and Biochemistry at the University of Houston, and their research teams applied computational and mathematical tools to this biological question. As described in this publication, they discovered the rate at which the cell grows may serve as a signal of starvation, triggering spore formation. This work could lessen food spoilage and control food-borne pathogens by offering new ways to inhibit sporulation in close relatives of B. subtilis that live on food.

This work is partially funded by the Systems and Synthetic Biology Cluster of the Division of Molecular and Cellular Biosciences, Awards #MCB – 1244135 and #MCB – 1244423.

Diatoms (a unicellular photosynthetic microalgae) are an important part of food webs, especially in areas of the ocean with an abundance of fish frequented by the fishing industry. Because conditions and availability of environmental resources change, diatoms regulate physiological functions (such as the carbon-concentrating mechanisms (CCMs) and photorespiration previously described) at the level of gene expression. Instead of focusing on one environmental condition or type of diatom, Dr. Justin Ashworth (Post-doctoral Fellow),  Dr. Monica Orellana (Principal Scientist) and Dr. Nitin Baliga (Senior Vice President and Director) of the Institute for Systems Biology integrated all publicly available microarray data (displaying gene expression levels) from multiple conditions for the model diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum to look for trends. As described in this publication and in the resulting integrative analysis available online at the Diatom Portal, the research team uncovered common patterns of gene expression and function. They also identified potential cis-regulatory DNA sequence motifs and distinct regions induced in response to changes in ocean pH levels and the availability of nitrate, silicic acid, and carbon. A greater understanding of this fundamental level of regulation enables scientists to better support diatoms in their role as biogeochemical nutrient recyclers.

This work is partially funded by the Cellular Dynamics and Function Cluster of the Division of Molecular and Cellular Biosciences, Award #MCB – 1316206.

As we previously described on the MCB Blog, the laboratory of Dr. Alexander Mankin and Dr. Nora Vázquez-Laslop at the Center for Biomolecular Sciences, University of Illinois – Chicago, studies fundamental mechanisms in protein synthesis. Ribosomes inside the cell read three mRNA nucleotides at a time (a reading frame) during protein synthesis (translation). Sometimes, the ribosome slips one or two nucleotides on the mRNA to a different reading frame (frameshift). Recent work on the E. coli bacterial copper transporter gene (copA) by Drs. Mankin, Vázquez-Laslop, and their research team uncovered a slippery sequence in the mRNA that led to “programmed frameshifts.” Depending on whether or not the ribosome slipped, two different proteins were made – a previously unidentified copper chaperon protein or a copper transporter protein. Together, the copper chaperon and transporter proteins help protect the bacterial cell from internalizing too much copper. This work provides new insight into how bacteria change gene expression in different environmental conditions and offers training for student researchers such as lead author Sezen Meydan, who was highlighted in the ‘Meet the Author’ section of Molecular Cell.

This work is partially funded by the Genetic Mechanisms Cluster of the Division of Molecular and Cellular Biosciences, Awards #MCB – 1244455 and #MCB – 1615851.

MCB WELCOMES DR. EJ CRANE, PROGRAM DIRECTOR FOR THE SYSTEMS AND SYNTHETIC BIOLOGY CLUSTER

EJ is sitting on the ground in front of a laptop, several open books and papers, as well as boxes and electrical equiptment. He is sitting in sand near a large log and has electrodes connected to wires several feet away in an expanse of smoldering ash.

Photo Credit: Fotios Kafantaris

What were you doing before you came to the NSF?

I am a Professor in the Department of Biology at Pomona College in southern California, and teach biochemistry, microbial ecology, and cell biology courses. My research team and I study the microbiology and biochemistry of sulfur-based respiration in natural environments, such as sediment from the deep sea and mud volcanoes from hot springs.

What attracted you to work for the NSF?

I enjoyed serving as a panelist on merit review panels. As a panelist, I saw so much new science and the intensity of going over proposals in detail in a relatively short period of time appealed to me. Also, it seemed like being a program officer would be a real challenge. It is so different from the experience that one has as a professor – where you can still feel very isolated even though you are interacting with your research group and a lot of students.

What was your first impression of the NSF? Has this impression changed since you began serving as a rotator?

My first impression after serving on merit review panels was positive; it hasn’t changed. Coming to NSF as a rotator was a pretty big move for me, so I researched the position. I asked questions when I visited the NSF and talked to former program officers that I know – everyone said that it’s a hard job, but that it’s worth doing due to the amount you learn and the ability to impact the direction that science takes.

What personal goals would you like to accomplish while at the NSF?

In the past, I tended to focus on scientific areas directly related to my research, so I’m hoping to learn to think much more broadly about where the natural and physical sciences are going and how different disciplines collaborate and complement each other. I’d also like to think more about where science could be going in the future.

What has surprised you most about working at the NSF?

What surprised me is the amazing efficiency of NSF. From the staff handling the logistics of the proposals and review panels, to the person running the office, to the IT staff – anytime you have a question or problem it gets dealt with immediately and correctly. It makes it much easier for program directors to focus on science.

What are some of the challenges of serving as a rotator?

I think the biggest challenge so far is not having my research lab right next door where I can go and be a part of my students’ daily lives and work when I get tired of being in my office. For me, much of the fun of science is working in the lab, so I miss not having cultures to look at in the microscope, not being able to spend a few hours with my students constructing and troubleshooting an experiment, or even the excitement of viewing new results such as looking through sequencing data to see what kinds of new microbes we may have discovered.

What would you tell someone who is thinking about serving as a Program Director at the NSF?

I’d tell them that if they’ve had experience with the merit review process as a panelist or reviewer and enjoyed it, they would most likely be a good fit at NSF. Having experience writing proposals is also important – if a person does not enjoy writing proposals, they’re probably not going to enjoy looking at them all day long!

When friends or colleagues find out that you work at the NSF, what do they say or ask?

I was kind of surprised at their responses. Almost everyone asks, “So what is your average day like? What do you actually do all day?”

MCB AT YOUR MEETING: ‘FINDING YOUR INNER MODELER’ AS A CELL BIOLOGIST

This image shows a blue and yellow flyer with the drawing of a cell beside the title that announces the ‘Finding Your Inner Modeler’ workshop at the University of Illinois on July 13, 2017. The workshop was funded by NSF MCB. Participants can register for free by April 15, 2017 at http://tinyurl.com/NSFmodelingworkshop. Support for travel and lodging expenses are available for a limited number of participants. Graduate students, post-doctoral researchers, and under-represented minorities at all career stages are strongly encouraged to apply. For information, contact Dr. David Stone at dstone@uic.edu.

Join us on July 13, 2017 at the University of Illinois at Chicago for a one-day workshop entitled “Finding Your Inner Modeler.” Funded by MCB, this is the first in a series of one-day workshops offered over the next three years and organized by Dr. David Stone, Professor, Department of Biological Sciences at University of Illinois at Chicago.

This workshop series was designed to help cell biologists with no experience in modeling gain confidence and build fruitful collaborations with computational experts. As Dr. Richard Cyr, MCB Program Director in the Cellular Dynamics and Function (CDF) cluster, notes, “With increasing frequency, successful NSF proposals integrate computational models with experimental work. Many researchers want to learn how to apply them to their research in a meaningful way, but are unaware of the new tools that are available and where they can begin their modeling efforts.” Dr. Stone continues, “A primary goal of the year one workshop is to promote new collaborations between cell biologists and experienced computational modelers.” One of the co-organizers of the workshop, Dr. Liz Haswell, an Associate Professor in the Department of Biology at Washington University in St. Louis says, “One of the unique aspects of this workshop is our match-making website that will help biologists and modelers pair up to solve complex problems in cell biology.” In years two and three of the workshop, participants will be invited to present their collaborative projects to computational and systems biology experts. Dr. Cyr adds, “We want to build a large and robust community of researchers who can help one another with their projects.”

Please register by April 15, 2017   http://tinyurl.com/NSFmodelingworkshop

There is no fee to register. Travel and lodging support for a limited number of eligible participants is available. Registrations received by April 15, 2017 will have full consideration for the limited travel and lodging support.

Graduate students, post-doctoral researchers, and under-represented minorities at all career stages are strongly encouraged to apply.

Keynote addresses will be presented by Dr. Wallace Marshall (University of California, San Francisco) and Dr. Rob Philips (California Institute of Technology).

Other presenters and panelists include: Dr. Mary Baylies (Memorial Sloan-Kettering Cancer Center), Dr. Angela DePace (Harvard University), Dr. Leslie Loew (University of Connecticut), Dr. Carlos Lopez (Vanderbuilt University), Dr. Alex Mogilner (New York University), Drs. Ben Prosser and Vivek Shenoy (University of Pennsylvania), Dr. Max Staller (Washington University in St. Louis), Dr. Marcos Sotomayor (Ohio State University), and Dr. Shelby Wilson (Morehouse College).

For a detailed schedule of events, go to https://pages.wustl.edu/haswell/finding-your-inner-modeler. For additional information, please contact Dr. David Stone at dstone@uic.edu.

To search for an interdisciplinary collaborator, sign up at the workshop’s collaborator-matching website: https://compmodelmatch.github.io/main/ (starting May 1, 2017).

SHARING MCB SCIENCE: UNRAVELING THE DYNAMICS OF TRANSMEMBRANE PROTEINS

Alt Caption (for ADA compliance): Undergraduate honors student Armin Mortazavi, wearing a blue dress shirt, and faculty mentor Dr. Roger Koeppe, wearing a black suitcoat, dress shirt, and glasses, are seated in a laboratory in front of a computer screen looking at deuterium nuclear magnetic resonance data (not shown).

An alpha helix is a stretch of amino acids coiled in three-dimensional space, similar to a spring, which can serve a variety of functions in transmembrane proteins (proteins that span the membrane of a cell). For example, a protein may be anchored into the membrane by one or more alpha helices. Or, since alpha helices physically link the interior and exterior of the cell, they can stimulate the initiation of a signaling cascade inside the cell in response to an external binding event. In addition, multiple alpha helices bundled together can form a channel, enabling ions to move across the hydrophobic interior of the cell membrane where they are otherwise excluded. These are just a small sample of the large number of biological processes and pathways thought to involve alpha helices in transmembrane proteins; therefore, researchers like Dr. Roger Koeppe II and his students are studying alpha helices to fill in the gaps in our fundamental understanding of the dynamics of transmembrane proteins.

One such gap involves identifying the factors that stabilize tilted transmembrane alpha helices. Alpha helices display a variety of orientations within a membrane. Some may reside in the membrane vertical to its axis; others tilt across the membrane at different angles. In his lab in the Department of Chemistry and Biochemistry at the University of Arkansas, Fayetteville, Dr. Koeppe and his students established an experimental model and used a biophysical technique to determine the positions of amino acid residues inside tilted alpha helices in a membrane environment.

In a recent publication, the team described their efforts to design, synthesize, and purify a series of nearly-identical peptides (23 amino acid strands that only varied slightly in amino acid composition). At the ends of each peptide, the team placed deuterium (radioactive isotope) labels on two alanine amino acid residues (at positions 3 and 21). When the team exposed these peptides to lipids (fatty acids that compose the interior of a cell membrane), they formed tilted alpha helices. Using a technique called solid-state deuterium nuclear magnetic resonance (NMR), a series of spectra were gathered for each helix.

As the cover for the March 2016 issue of ChemBioChem depicts, the team detected a deviation between actual and expected orientations of the deuterium-labeled alanine residues at positions 3 and 21 – they actually appeared far from their expected orientations as part of the alpha helix (blue curve). In this way, Dr. Koeppe and his research team discovered that the first and last few amino acids at each end of the tilted alpha helix were unraveled from and no longer part of the alpha helix.

A driving force behind the formation of an alpha helix is the increased stability that results from numerous interactions between the amino acids in the helix, so unraveling these interactions at the ends of the helix may seem to disrupt stability. However, Dr. Koeppe and his team noted that unwinding the helix at both ends creates a larger surface area, enabling new interactions to occur between the amino acids in the helix and the surrounding membrane lipids – providing additional conformational stability in support of the tilt and limiting the helix’s motion. These research findings contribute to our understanding of fundamental biological processes including lipid-protein interactions, membrane protein stability, and membrane biophysics.

When asked about the broader impacts of his research, Dr. Koeppe responded:

“Notably, much of this research involved an undergraduate honors student, Armin Mortazavi. The opportunities for undergraduate students to conduct cutting-edge research alongside graduate students provide students with valuable hands on experience, exposure to new techniques, and mentoring at an early stage in their scientific careers. We have also increased the exposure of communities in Arkansas to science – establishing science cafés and statewide infrastructure projects such as a laboratory where you can explore proteins using virtual reality technology. These efforts broaden the participation of non-traditional or underrepresented groups in science.”

This work is partially funded by the Molecular Biophysics Cluster of the Division of Molecular and Cellular Biosciences, Award #MCB – 1327611.

A Word from Dr. Theresa Good, Acting Division Director

tgood-photo

As many of you may know, our Division Director, Dr. Linda Hyman, recently returned to her previous position as Associate Provost for the Division of Graduate Medical Sciences at Boston University. Linda led MCB through some difficult times: the death of a dear friend and colleague, Dr. Kamal Shukla; the retirement of a dedicated colleague and advocate for the synthetic biology community, Dr. Susanne Von Bodman; and the transition of a number of staff members into different roles within the Foundation and elsewhere in federal service. From all of us at MCB, thank you Linda, for the time you took away from your role at Boston University to lead us and for your year and a half of service to the Foundation. Good luck as you return back to Boston University.

As I now take on the role of Acting Division Director, I am thankful to have the support of talented program directors, staff, and colleagues, like Dr. Gregory Warr, who have previously served in this role.  All are dedicated to the NSF mission of transforming the frontiers of science and engineering, and stimulating innovation to address societal needs through research and education. While change is occasionally uncomfortable, it often brings about opportunities. We are excited to have a number of new program directors who you will meet over the coming months (Dr. E.J. Crane, Dr. Michael Weinreich, and Dr. Jarek Majewski), new staff members (Grace Malato), and the expert leadership of a new Operations Manager (Dr. Reyda Gonzalez-Nieves). Two of our dedicated program directors, first Dr. Michelle Elekonich, and then Dr. Karen Cone, will serve as the acting Deputy Division Director in two respective 120 day rotations. Michelle and Karen both have experience in division leadership and will work with me to ensure the efficient operations and attention to science vision for which MCB is known.

In addition, a new solicitation will be issued and some new workshops are being developed to catalyze conversations about the future directions of MCB science. Within MCB, we are poised to do our part to invest in science, engineering, and education for the nation’s future.

We look forward to engaging the scientific community during panels, meetings, and outreach visits about how to best serve science and the needs of the nation. We ask you to continue to work with us by: submitting your best ideas in proposals, continuing to participate in peer review, serving on panels, meeting with us at NSF workshops or at other scientific meetings, serving as rotating program directors, continuing to do outstanding research and broader impacts activities, and communicating the results of those efforts to the broader community.

As always, MCB welcomes your questions and input on how we can better serve the scientific community. You should always feel free to give us feedback or reach out to a program director with questions.

 

Best wishes,

 

Dr. Theresa Good

Acting Division Director