MCB

A photo of Alexis Patullo in her graduation gown for George Mason University. Alexis is standing in front of a fountain and holding green and yellow pom-poms.

WELCOME TO MCB ALEXIS PATULLO!

Hear from Program Assistant Alexis Patullo.

What is your educational background?

I recently graduated from George Mason University with a bachelor’s degree in Forensic Science and a minor in Biology.

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

I started working at NSF in September 2015 as a Pathways Student in the Office of the Assistant Director for the Directorate for Biological Sciences. Later that year, I transitioned to a detail position, which is a short term preview of another role that develops new skills, within the Division of Molecular and Cellular Biosciences (MCB). Upon graduation, I was eligible for a Program Assistant position in MCB, and I applied because I thoroughly enjoyed my detail in the Division. As a Program Assistant, I support the Genetic Mechanisms (GM) and Systems and Synthetic Biology (SSB) programs.

What attracted you to work for NSF?

I often walked through the NSF atrium on my way to another job. Every time I thought, I should stop in to see what NSF is all about. As I looked for student internships on USAJOBS.gov, I came across a Pathways position at NSF. After reading more about what NSF does and finding out that several of my professors were either awarded NSF funding or served as NSF Program Directors, I decided to apply. It seemed like a great opportunity to put the skills I have to good use while taking classes and continuing to learn about science.

What have you learned so far from your position?

I think one of the most important things I have learned is the importance of teamwork and effective communication as most tasks involve several people and moving parts. Learning new technologies and procedural changes that reflect updated policies or regulations means that most days I feel like I learn something new in my position.

MCB AT YOUR MEETING: OUTREACH AT THE UNIVERSITY OF PUERTO RICO AT CAROLINA

Image of Dr. Jose Garcia (Investigator at UPRC), Dr. Karilys González Nieves (Investigator at UPRC), Dr. Luis Cubano (Co-Project Director, UPRC Title V), Dr. Reyda González-Nieves (MCB Acting Operations Manager), Dr. Larry Halverson (SSB Program Director), Ms. Raquel Marti (Project Director, UPRC Title V), Dr. Linda Hyman (MCB Division Director), Dr. Wilson Francisco (MB Program Director), Dr. Jose Alvarez (Faculty Development, UPRC Title V), Dr. Moisés Orengo Avilés (UPRC Chancellor), Dr. Awilda Nueñez (Academic Dean at UPRC), and Dr. Jose Santiago (Investigator at UPRC)

Workshop Coordinators and Presenters (from left): Dr. Jose Garcia (Investigator at UPRC), Dr. Karilys González Nieves (Investigator at UPRC), Dr. Luis Cubano (Co-Project Director, UPRC Title V), Dr. Reyda González-Nieves (MCB Acting Operations Manager), Dr. Larry Halverson (SSB Program Director), Ms. Raquel Marti (Project Director, UPRC Title V), Dr. Linda Hyman (MCB Division Director), Dr. Wilson Francisco (MB Program Director), Dr. Jose Alvarez (Faculty Development, UPRC Title V), Dr. Moisés Orengo Avilés (UPRC Chancellor), Dr. Awilda Nueñez (Academic Dean at UPRC), and Dr. Jose Santiago (Investigator at UPRC)

MCB Program Directors and Division leadership regularly attend scientific meetings and workshops to garner input from the scientific community, spread the word about funding opportunities, recruit panelists, and otherwise provide information to encourage the submission of grant proposals. In September, Dr. Linda Hyman (MCB Division Director), Dr. Wilson Francisco (MCB Program Director for Molecular Biophysics (MB)), Dr. Larry Halverson (MCB Program Director for Systems and Synthetic Biology (SSB)), and Dr. Reyda González-Nieves (MCB Acting Operations Manager) traveled to Puerto Rico to support the “How to Write an Excellent Proposal” workshop hosted by the University of Puerto Rico at Carolina (UPRC).

This workshop provided an overview of the National Science Foundation (NSF) and MCB, discussed best practices in NSF grant writing and submission, and highlighted funding opportunities in MCB and across NSF. Prior to the start of the workshop, Drs. Hyman, Francisco, and Halverson met with workshop coordinators at the University of Puerto Rico at Carolina to strategize how best to conduct personalized outreach during the workshop given the larger than expected number of registrants. The workshop was attended by over 60 participants from eight different institutions throughout the island of Puerto Rico. During the morning session of the workshop, MCB representatives gave three presentations: “Overview of NSF and the Directorate for Biological Sciences,” “Cluster Overviews and Opportunities between MCB and other Divisions/Directorates,” and “How to Write an Excellent Proposal.”

Image of MCB Workshop Presenters: (top) Dr. Linda Hyman; (bottom left) Dr. Wilson Francisco; and (bottom right) Dr. Larry Halverson

MCB Workshop Presenters: (top) Dr. Linda Hyman; (bottom left) Dr. Wilson Francisco; and (bottom right) Dr. Larry Halverson

These presentations were followed by individual meetings between MCB representatives and PIs, faculty, and graduate students from the University of Puerto Rico at Carolina to discuss project ideas and their fit for funding opportunities within MCB and NSF. These personalized sessions provided attendees the opportunity to have their questions answered by MCB experts, and to get to know MCB Division Leadership, Program Directors, and staff. In post-workshop feedback, attendees rated their experience “excellent.”

Drs. Hyman, Francisco, Halverson, and González-Nieves felt this workshop was a unique opportunity to encourage new collaborations, cultivate new ideas, discuss funding opportunities, and keep inspiring new and undiscovered talent in the scientific community. The Division of MCB would like to thank the University of Puerto Rico at Carolina for hosting MCB at Your Meeting. To find out about our future travel plans, visit the “MCB at Your Meeting” page on the MCB Blog.

SHARING MCB SCIENCE: REGULATING NITROGENASE FORMATION IN CYANOBACTERIA

thiel-1b

Cyanobacteria are blue-green colored microbes with a simple cellular structure (like bacteria) and the ability to convert sunlight into chemical energy through photosynthesis (like plants). They also perform nitrogen fixation, a process by which nitrogen is extracted from the air and converted into ammonia, using an enzyme (a specialized protein) called nitrogenase. Since ammonia is a potent plant fertilizer, cyanobacteria can live symbiotically with plants in a variety of soil, water, and marsh habitats – enabling some farmers to use cyanobacteria in place of traditional fertilizers to improve the yields of rice and other staple food crops. Because of its function in nitrogen fixation, research on nitrogenase has the ability to create a firm foundation for future advances in agriculture and food security in support of the NSF’s mission to “…advance the national health, prosperity, and welfare…”

Associate Dean Dr. Teresa Thiel and her lab in the Department of Biology at the University of Missouri – St. Louis study a type of cyanobacteria called Anabaena variabilis. Uniquely, this cyanobacterium has three different nitrogenase enzymes, each capable of performing nitrogen fixation in different environmental conditions. The Thiel team previously studied each of the three nitrogenases and characterized a group of fifteen genes (called the nif1 gene cluster) whose expression through transcription (DNA to RNA) and translation (RNA to protein) is necessary to make the primary nitrogenase in Anabaena variabilis. They also identified potential sites of regulation; cells often regulate discrete steps in the protein production process as a way to conserve cellular resources by limiting the amount of protein produced when it is not needed. For years, scientists knew the important role nitrogenase played in nitrogen fixation, but had yet to uncover how cyanobacterial regulation of production of this important enzyme.

In a recent publication, Dr. Thiel and her team describe their research on one regulatory site called an RNA stem-loop. The investigators predicted this secondary structure would occur before an important gene in the nif1 cluster (called nifH1). The nifH1 gene encodes a protein largely responsible for nitrogenase enzyme assembly and function. Using a process called polymerase chain reaction (PCR) to mutate the RNA stem-loop, they studied how changes in the stem-loop altered nifH1 transcript stability and processing. The Thiel team found that mutations impacting the structure or sequence of the RNA stem-loop also severely inhibited the levels of nifH1 transcript, and most importantly, limited cyanobacteria’s ability to perform nitrogen fixation.

These findings have potential for modulating the efficiency of nitrogen fixation in cyanobacteria, leading to more fertilizer production, and a potential source of renewable energy by harnessing the hydrogen created during nitrogen fixation. This work also may impact an exciting area of bioengineering research. As described in a MCB awarded US and UK research BBSRC-collaboration Ideas Lab proposal, bioengineers are attempting to create a “nitroplast” cellular structure, patterned after the nitrogenase in cyanobacteria, to allow plants to make their own fertilizer.

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

The engagement of scientists with the larger scientific and non-scientific community is critical to promoting a public understanding of science and in attracting students to careers in science. To do so, the broader impacts of my research include integrating research within graduate, undergraduate, and high school education. Students from Jennings Senior High School, a predominantly African-American high school located in North St. Louis County, have participated in 6 weeks of summer research as part of the Jennings at UMSL Program, which is designed to help students succeed in college. Additionally, a student from the UMSL SUCCEED program, which supports vocational experiences for students with intellectual or developmental disabilities works as a laboratory aide in my lab. Furthermore, I participate in educational outreach activities in the St. Louis community, working with local high school teachers to incorporate hands-on microbiology activities in their classrooms.

This work is partially funded by the Division of Molecular and Cellular Biosciences, Award #MCB-1052241.

MCB WELCOMES DR. CASONYA JOHNSON, PROGRAM DIRECTOR FOR THE GENETIC MECHANISMS CLUSTER

Casonya Johnsonbiology

What were you doing before you came to the NSF?

I am an associate professor in the Department of Biology at Georgia State University. I teach courses in genetics to students at all levels and conduct research with my students to investigate the underlying mechanisms by which transcriptional regulators direct post-embryonic development—in other words, we want to understand how the molecules that regulate the process of making RNA from DNA affect the development of an organism after the embryo stage.

What attracted you to work for NSF?

I was attracted by the opportunity to be at the forefront of cutting edge research, to expand my own knowledge of my research field, and to understand how funding trends are directed.

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

My first impression was that the impact of NSF (on science as a whole) extends far beyond the individual research laboratory. I have only been here a month, but my impression stands.

What are the personal goals you most want to accomplish while at NSF?

I want to learn as much as I can, about everything I can; to find ways to broaden my research focus; to find ways to communicate to the research community the ways in which NSF supports research; and to find ways to better engage the general public so that everyone can understand the need for and benefits of basic scientific research.

What has surprised you most about working at NSF?

I think I am most surprised about how much support – from IT to administrative to security – is offered here. That type of support is sometimes missing in academia, so I am used to spending time trying to figure things out for myself, when here all I need to do is ask for help.

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

The learning curve is very steep. The biggest challenge is fighting the feeling that I’m not moving fast enough to get things done. The other challenge is making sure that my students and my personal research do not suffer while I am here.

What would you tell someone who is thinking about serving as a program director at NSF?

Do it! Your colleagues at NSF will help you succeed and at a minimum, you will leave with a much better understanding of how NSF works.

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

All have responded “What an amazing opportunity!” Then, they ask if I like it and who is taking care of my lab.

SHARING MCB SCIENCE: DISCOVERY OF A NON-BASE FLIPPING MECHANISM IN DNA REPAIR

Eichmangroup1

Eichman Lab members involved in the study (from left to right): Dr. Elwood Mullins, Dr. Brandt Eichman, Rongxin Shi, and Dr. Zachary Parsons. Photo Credit: Susan Urmy/Vanderbilt

The DNA of humans, like that of all other organisms, can be damaged, acquiring what are referred to as “lesions.” A common form of DNA damage is DNA alkylation, where a small group of carbons and hydrogens (alkyl group) are chemically bound to the base of DNA nucleotides (the As, Ts, Cs, and Gs that make up DNA). When a DNA base is alkylated, the normal function of the cell’s DNA is disrupted and the genetic information being stored is mutated, which has the potential to develop into some types of cancer and threaten the survival of the organism.

To protect the organism from the effects of DNA lesions, cells have processes to repair DNA. One such process is called base excision repair, which was one subject of last year’s Nobel Prize in Chemistry. As shown in the figure below, base excision repair begins with DNA glycosylase (ie. a protein with enzymatic function that initiates a process), which is able to bind to double-stranded DNA and look for DNA lesions using a base-flipping mechanism. In base-flipping, a DNA nucleotide that is suspected of containing an alkyl group is flipped away from its base pair partner and into the active site of the DNA glycosylase. If the DNA glycosylase sees a lesion, it severs the chemical bond that links the DNA base to the DNA backbone and initiates subsequent repair steps, ultimately restoring the DNA to an undamaged state.

Until recently, it was thought that all DNA glycosylases used base-flipping to repair damaged DNA. A paradigm shift occurred in the DNA repair field when a non-base-flipping DNA glycosylase enzyme, called AlkD, was discovered by Professor Dr. Brandt Eichman in the Department of Biological Sciences and Center for Structural Biology at Vanderbilt University and his research group, in collaboration with Professor Dr. Sheila David and her research group at University of California Davis and Professor Dr. Yasuhiro Igarashi at the Toyama Prefectural University in Japan. Repair that does not involve base-flipping has also been shown by the Eichman team to uniquely allow the repair of bulky DNA lesions.

research-summary.png

Space-filling models (left) and illustrations (right) showing base-flipping excision repair (top) and non-base-flipping excision repair (bottom). Top: A damaged DNA base (blue) from a double stranded DNA helix (orange and yellow) is inserted, or “flipped,” into the active site of the DNA glycosylase enzyme (white or grey). Bottom: A bulky chemical group (purple) attached to a DNA base (blue) results in a lesion within a double stranded DNA helix (orange and yellow) that is repaired without base-flipping by a DNA glycosylase enzyme (AlkD) (white or grey).

As described in a recent publication in Nature, the Eichman research team used a technique called X-ray crystallography to capture a series of time-lapsed 3D renderings of AlkD as it repaired a lesion. The Eichman team’s conclusion that AlkD removes DNA damage using a non-base-flipping mechanism was supported by their crystallographic analysis which showed the AlkD enzyme mainly contacted the DNA backbone, not the DNA lesion. Thus, non-base-flipping broadens the spectrum of DNA damage that DNA glycosylases are known to repair. Also, the 3D structure of AlkD is common to proteins that do not have enzymatic functions, which makes it difficult for researchers to identify non-base-flipping DNA glycosylases just based on their structure. Therefore, there is a strong possibility there are other DNA repair proteins that scientists have yet to identify.

When asked about the broader impacts of his research, Dr. Eichman responded: “This research program has involved trainees from all levels—undergraduate, graduate, and postdoctoral—several of whom have continued on in a number of scientific careers, including medical school, science policy, and industry. Most importantly, it has enabled us to expose undergraduates to cutting edge structural biology and to the practical aspects of X-ray crystallography, both in the classroom and in the lab.”

This work is funded jointly by the Genetic Mechanisms program in the Division of Molecular and Cellular Biology (MCB) and the Chemistry of Life Processes Program in the Division of Chemistry in the Directorate of Mathematical and Physical Sciences, Award #MCB-1122098 and Award #MCB-1517695.

FAREWELL TO DR. MANJU HINGORANI

manju farewell 2

First Row (Left to Right): Dr. Karen Cone, Dr. Theresa Good, Dr. Manju Hingorani, Dr. Charlie Cunningham; Second Row (Left to Right): Keshanti Tidwell, Dr. Stacy Kelley, Dr. Linda Hyman, Dr. Susanne von Bodman, and Dr. Wilson Francisco

The Division of Molecular and Cellular Biosciences (MCB) gave a warm send off to Dr. Manju Hingorani, former Program Director in the MCB Genetic Mechanisms program.

During her two year tenure at the NSF, Dr. Hingorani worked with investigator-driven proposals submitted to both the Genetic Mechanisms and the Cellular Dynamics and Function programs. As a rotating Program Director, Dr. Hingorani managed proposal reviews and awards and responded to inquiries from principal investigators conducting fundamental research related to the central dogma of biology. Dr. Hingorani noted she particularly enjoyed managing CAREER proposal reviews because it gave her glimpses of potential future leaders in science and education. Dr. Hingorani also aided in the review of NSF Graduate Research Fellowship Program proposals, appreciating the chance to serve in a program that has benefitted students from her home institution.

As Dr. Hingorani returns to her position as Professor of Molecular Biology and Biochemistry at Wesleyan University, she looks forward to reconnecting with her students “in 3D,” in her laboratory, and in classes. Unfortunately for us, she will take most of her Swiss chocolate stash back with her!

MCB would like to thank Dr. Manju Hingorani for her service, and we wish her all the best in the future. If you are interested in serving like Dr. Hingorani as a rotating MCB Program Director, please contact us at 703-292-8440 and read the rotator Dear Colleague Letter.

Welcome to MCB Ann Larrow!

Hear from Program Specialist Ann Larrow

What is your educational background?

I have an Associate degree in science lab technology with a concentration in histotechnology; a BA in History; and an MS in Organizational Development and Leadership (a cross-disciplinary degree from Sociology and Political Science). I recently completed coursework for the Project Management Professional certification and have taken a variety of other self-study classes over the years.

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

I started as a Program Specialist with MCB on July 11, 2016.

What attracted you to work for NSF?

I was looking for a position where I could continue building a solid resume for professional development. Learning that MCB is interested in creating/maintaining a flexible, adaptable organization by staffing it with creative, forward-looking people was intriguing.

What have you learned so far from your position?

I was impressed with the professionalism of employee orientation; loved hearing HR refer to new hires as “Top Talent,” then following up by inviting us to attract similar talent by updating our Linked In profiles; and have been thrilled with the reception and helpfulness of staff members throughout the building. I have been impressed with what I’ve seen of how the organization uses technology to manage processes and look forward to learning more about where it works best, where it doesn’t work as well, and helping to plan and implement improvements. As for my job duties…ask me in a month or so.