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

SHARE YOUR IDEAS ON CYBERINFRASTRUCTURE

A new NSF Dear Colleague Letter (DCL; NSF 17-031) has been posted: Request for Information on Future Needs for Advanced Cyberinfrastructure to Support Science and Engineering Research (NSF CI 2030).

From the DCL:

“NSF Directorates and Offices are jointly requesting input from the research community on science challenges and associated cyberinfrastructure needs over the next decade and beyond. Contributions to this Request for Information will be used during the coming year to inform the Foundation’s strategy and plans for advanced cyberinfrastructure investments. We invite bold, forward-looking ideas that will provide opportunities to advance the frontiers of science and engineering well into the future.”

We encourage MCB to weigh in – what do you see as the cyberinfrastructure that will be needed to advance molecular and cellular biosciences?

The DCL points to an external submission website (http://www.nsfci2030.org/). Please note that the deadline for submissions is April 5, 2017 5:00 PM ET. Questions about this effort and the submission process should be sent to Dr. William Miller, Office of Advanced Cyberinfrastructure, at this email address: nsfci2030rfi@nsf.gov.

CONGRATULATIONS TO 2017 PRESIDENTIAL EARLY CAREER AWARDEE, DR. AHMAD KHALIL!

Dr. Ahmad Khalil is smiling, arms crossed, standing in front of his lab bench while wearing a blue and white checked shirt and glasses.

MCB would like to congratulate Dr. Ahmad (Mo) Khalil, recipient of the 2017 Presidential Early Career Award for Scientists and Engineers (PECASE). The PECASE award is the most prestigious honor a scientist or engineer can receive from the U.S. government early in their independent research career.

PECASE selection is a highly competitive process. As we previously noted on the MCB Blog, awardees must first receive a Faculty Early Career Development (CAREER) award. Dr. Khalil received his CAREER award from the Systems and Synthetic Biology Cluster in the Division of MCB. The National Science Foundation annually nominates up to twenty CAREER awardees for the PECASE award, and the White House Office of Science and Technology Policy makes the final selection of PECASE awardees.

Dr. Khalil was selected to receive a PECASE award because his work is an outstanding example of innovative research at the frontiers of science and technology and because of his strong commitment to service, scientific leadership, education, and outreach. His research uses synthetic biology to engineer cellular networks; the specific focus of his CAREER award is to develop synthetic tools to study the function of prions in yeast cells and populations. You can read more about his research at Boston University on his lab’s website or in a post we featured via the Share MCB Science blog theme.

Please join us in congratulating Dr. Khalil!

This work is partially funded by the Systems and Synthetic Biology Cluster of the Division of Molecular and Cellular Biosciences, CAREER Award #MCB-1350949.

WELCOME TO MCB GRACE MALATO!

Grace is looking into the camera and smiling. There are tropical trees in the background and she is wearing a gray tshirt and holding a green sive full of Rhoadsia altipinna, a small western Ecuadorian Tetra fish which appear rainbow.

Hear from MCB biologist Grace Malato.

What is your educational background?

I received my Bachelor of Science degree in Wildlife Biology with an emphasis in Aquatics from the University of Montana, Missoula. I then received my Master of Science degree in Biology from DePaul University in Chicago, Illinois.

What is your position? When did you start working in MCB?

I started as a Biologist for MCB in January 2017, just after the New Year. I am here as a Presidential Management STEM Fellow (PMF STEM), which is a program that we previously featured on the MCB blog.

What attracted you to work for NSF?

I have had the opportunity to work in a variety of research settings that combine molecular tools with ecological concern; I love the excitement that comes with discovery. After seeing how important but challenging interdisciplinary research can be, I was curious about the bigger picture. I am excited to work at NSF to contribute to the scientific community at large and to be a part of an organization providing critical funding for innovative research.

What have you learned so far from your position?

I have learned, in my short time at NSF, so much about the inner workings of the merit review process as well as how funding and research priorities are set. I have learned just how much work goes into reviewing proposals as well as how decisions on funding influence the future of science.