Genomic Gymnastics of a Single-Celled Ciliate and How It Relates to Humans

Laura Landweber
Credit: Denise Applewhite.
Laura Landweber
Grew up in: Princeton, New Jersey
Job site: Columbia University, New York City
Favorite food: Dark chocolate and dark leafy greens
Favorite music: 1940’s style big band jazz
Favorite hobby: Swing dancing
If I weren’t a scientist I would be a: Chocolatier (see “Experiments in Chocolate” sidebar at bottom of story)

One day last fall, molecular biologist Laura Landweber Link to external web site surveyed the Princeton University lab where she’d worked for 22 years. She and her team members had spent many hours that day laboriously affixing yellow Post-it notes to the laboratory equipment—microscopes, centrifuges, computers—they would bring with them to Columbia University, where Landweber had just been appointed full professor. Each Post-it specified the machinery’s location in the new lab. Items that would be left behind—glassware, chemical solutions, furniture, office supplies—were left unlabeled.

As Landweber viewed the lab, decorated with a field of sunny squares, her thoughts turned to another sorting process—the one used by her primary research subject, a microscopic organism, to sift through excess DNA following mating. Rather than using Post-it notes, the creature, a type of single-celled organism called a ciliate, uses small pieces of RNA to tag which bits of genetic material to keep and which to toss.

Landweber is particularly fond of Oxytricha trifallax, a ciliate with relatives that live in soil, ponds and oceans all over the world. The kidney-shaped cell is covered with hair-like projections called cilia that help it move around and devour bacteria and algae. Oxytricha is not only bizarre in appearance, it’s also genetically creative.

Unlike humans, whose cells are programmed to die rather than pass on genomic errors, Oxytricha cells appear to delight in genomic chaos. During sexual reproduction, the ciliate shatters the DNA in one of its two nuclei into hundreds of thousands of pieces, descrambles the DNA letters, throws most away, then recombines the rest to create a new genome.

Landweber has set out to understand how—and possibly why—Oxytricha performs these unusual genomic acrobatics. Ultimately, she hopes that learning how Oxytricha rearranges its genome can illuminate some of the events that go awry during cancer, a disease in which the genome often suffers significant reorganization and damage.

Oxytricha’s Unique Features

Oxytricha carries two separate nuclei—a macronucleus and a micronucleus. The macronucleus, by far the larger of the two, functions like a typical genome, the source of gene transcription for proteins. The tiny micronucleus only sees action occasionally, when Oxytricha reproduces sexually.

Oxytricha trifallax cells in the process of mating
Two Oxytricha trifallax cells in the process of mating. Credit, Robert Hammersmith.

What really makes Oxytricha stand out is what it does with its DNA during the rare occasions that it has sex. When food is readily available, Oxytricha procreates without a partner, like a plant grown from a cutting. But when food is scarce, or the cell is stressed, it seeks a mate. When two Oxytricha cells mate, the micronuclear genomes in each cell swap DNA, then replicate. One copy of the new hybrid micronucleus remains intact, while the other breaks its DNA into hundreds of thousands of pieces, some of which are tagged, recombined, then copied another thousand-fold to form a new macronucleus. Continue reading

Computational Geneticist Discusses Genetics of Storytelling at Sundance Film Festival

About 10 years ago, University of Utah geneticist Mark Yandell developed a software platform called VAAST (Variant Annotation, Analysis & Search Tool) to identify rare genes. VAAST, which was funded by NHGRI, was instrumental in pinpointing the genetic cause of a mystery disease that killed four boys across two generations in an Ogden, UT family.

NIGMS has been supporting Yandell’s creation of the next generation of his software, called VAAST 2, for the past few years. The new version incorporates models of how genetic sequences are conserved among different species to improve accuracy with which benign genetic sequences can be differentiated from disease-causing variations. These improvements can help identify novel disease-causing genes responsible for both rare and common diseases.

Yandell and his colleagues in the Utah Genome Project recently took part in a panel at the Sundance Film Festival called the “Genetics of Storytelling” to discuss film’s ability to convey the power of science and medicine. Yandell told the audience his story about his efforts to use VAAST to trace the Ogden boys’ genetic variation back to their great-great-great-great-great grandmother.

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What Zombie Ants Are Teaching Us About Fungal Infections: Q & A with Entomologists David Hughes and Maridel Fredericksen

 

I can still remember that giddy feeling I had seven years ago, when I first read about the “zombie ant.” The story was gruesome and fascinating, and it was everywhere. Even friends and family who aren’t so interested in science knew the basics: in a tropical forest somewhere there’s a fungus that infects an ant and somehow takes control of the ant’s brain, forcing it to leave its colony, crawl up a big leaf, bite down and wait for the sweet relief of death. A grotesque stalk then sprouts from the poor creature’s head, from which fungal spores rain down to infect a new batch of ants.

A fungal fruiting body erupts through the head of a carpenter ant infected by a parasitic fungus in Thailand. Credit: David Hughes, Penn State University.

The problem is, it doesn’t happen quite like that. David Hughes Exit icon , the Penn State University entomologist who reported his extensive field observations of the fungus/ant interactions in BMC Ecology Exit icon, which caused much excitement back in 2011, has continued to study the fungus, Ophiocordyceps unliateralis, and its carpenter ant host, Camponotus leonardi.

In late 2017, Hughes and his colleagues published an article in PNAS Exit icon in which they used sophisticated microscopy and image-processing techniques to describe in great detail how the fungus invades various parts of the ant’s body including muscles in its legs and head.

Although Hughes’s earlier BMC Ecology paper showed fungus in the head of an ant, the new study reveals that the fungus never actually enters the brain.

To me, the new finding somehow made the fungus’ control over the ant even more baffling. What exactly was going on?

To find out, I spoke with Hughes and his graduate student Maridel Fredericksen.

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Interview With a Scientist: Joel Kralj, Electromicist

Every one of our thoughts, emotions, sensations, and movements arise from changes in the flow of electricity in the brain. Disruptions to the normal flow of electricity within and between cells is a hallmark of many diseases, especially neurological and cardiac diseases.

The source of electricity within nerve cells (i.e., neurons) is the separation of charge, referred to as voltage, across neuronal membranes. In the past, scientists weren’t able to identify all the molecules that control neuronal voltage. They simply lacked the tools. Now, University of Colorado biologist Joel Kralj Exit icon has developed a way to overcome this hurdle. His new technique—combining automated imaging tools and genetic manipulation of cells—is designed to measure the electrical contribution of every protein coded by every gene in the human genome. Kralj believes this technology will usher in a new field of “electromics” that will be of enormous benefit to both scientists studying biological processes and clinicians attempting to treat disease.

In 2017, Kralj won a New Innovator Award from the National Institutes of Health for his work on studying voltage in neurons. He is using the grant money to develop a new type of microscope that will be capable of measuring neuronal voltage from hundreds of cells simultaneously. He and his research team will then attempt to identify the genes that encode any of the 20,000 proteins in the human body that are involved in electrical signaling. This laborious process will involve collecting hundreds of nerve cells, genetically removing a single protein from each cell, and using the new microscope to see what happens. If the voltage within a cell is changed in any way when a specific protein is removed, the researchers can conclude that the protein is essential to electrical signaling.

In this video, Kralj discusses how he plans to use his electromics platform to study electricity-generating cells throughout the body, as well as in bacterial cells (see our companion blog post “Feeling Out Bacteria’s Sense of Touch” featuring Kralj’s research for more details).

Dr. Kralj’s work is funded in part by the NIH under grant 1DP2GM123458-01.

Two NIGMS MARC Scholars Receive Prestigious Rhodes Scholarship

Oxford University. Credit: Andrew Shiva, Wikimedia Commons CC BY-SA.

MARC U-STAR Scholars Jasmine Brown and Naomi Mburu were among 32 Americans to recently receive the prestigious Rhodes Scholarship at Oxford University in England. Rhodes Scholars are chosen for their academic and research achievements, as well as their commitment to others and leadership potential.

As current MARC U-STAR Scholars, Brown and Mburu are part of an NIGMS research training program for undergraduate junior and senior honor students. MARC is designed to increase the number of people from groups underrepresented in biomedical sciences by preparing students for high-caliber, doctorate-level training.

Here’s more about these two distinguished women:

Credit: The Source, Washington University in St. Louis.

Jasmine Brown, 21

Brown, of Hillsborough, New Jersey, is a senior at Washington University in St. Louis and works as a research assistant at the Washington University School of Medicine. There, she studies genes that are protective against mental defects that result from West Nile-induced brain inflammation. After she receives her bachelor’s degree in biology, she plans to earn a doctorate degree in neuroscience as a Rhodes Scholar at Oxford University.

In addition to her current training as a MARC Scholar, Brown has spent her summers as an undergraduate research assistant, engaging in the study of these other notable subjects:

  • Lung cancer, at the Broad Institute of MIT and Harvard (2017)
  • Specific drugs’ cough-suppressing effects, at Johns Hopkins University School of Medicine (2015)
  • Long-term neurological effects of cocaine and other stimulants on the teen brain, at the University of Miami Miller School of Medicine (2014)

“What I love about science is that it gives me tools to generate answers and to improve human health. It’s a fun process for me, but also a satisfying one because I can make an impact,” Brown said in a statement.

Equally important to her studies, Brown is a champion for other underrepresented students in the sciences. After her own experience as the target of prejudice, Brown started the Minority Association of Rising Scientists (MARS) to support underrepresented students participating in research and inform faculty members about implicit bias. With the help of the National Science Foundation, Brown is working to expand MARS nationwide.

Brown has given back to the community in other ways. She was a member of The Synapse Project Exit icon, which prepares high school students for a neuroscience competition called Brain Bee Exit icon. She was also a 2014-2015 candidate for Mx. WashU Exit icon, an organization that raises money for a children’s program called City Faces Exit icon.

Naomi Mburu, 21

Credit: Marlayna Desmond for UMBC.

Naomi Mburu, of Ellicott City, Maryland, is the daughter of Kenyan immigrants and the first student in the history of the University of Maryland Baltimore County (UMBC) to receive the Rhodes Scholarship. The senior in chemical engineering plans to complete a doctorate in engineering science and to research heat transfer applications for nuclear fusion reactors.

“I believe the Rhodes Scholarship will allow me to foster a stronger community amongst my fellow scholars because we will all be attending the same institution,” Mburu said in a statement.
Mburu is currently working with Gymama Slaughter Exit icon, UMBC associate professor of computer science and electrical engineering, to develop a machine that ensures human organs remain healthy as they await transplantExit icon.
During her recent summer internship with Intel, Mburu developed an interactive model to estimate the cost of coatings applied to equipment. Her work helped improve pricing negotiations and established additional cost estimates for other chemical processes.

Her other areas of research have included:

  • Assessing phosphate’s effects on the ribosomal protein L4 as a student at Mount Hebron High School
  • Measuring the impurities found in the Large Hadron Collider particle accelerator, at the European Organization for Nuclear Research, Geneva, Switzerland

Mburu’s aspirations involve not just science but education advocacy. Her passion for STEM Exit icon education and increasing diversity in STEM fields led to her current involvement as a MARC trainee, where she’s learned to communicate her desire to make a global impact through her science research and her efforts to remove barriers to education equality.

In her free time, Mburu has helped K-12 students with their homework during her time at UMBC. She continues to mentor youth and helps high school girls on STEM-related research projects.

How I Spent My Summer Vacation

One of NIGMS’ primary goals is to provide support to train the next generation of biomedical research scientists. In pursuit of this goal, NIGMS aims to enhance the diversity of the scientific workforce and develop research capacities throughout the country. NIGMS-administered training programs at the undergraduate level provide support for trainees underrepresented in the biomedical sciences to develop skills to successfully transition into doctoral programs. Three unique NIGMS-administered undergraduate-focused programs are highlighted below.

  • Building Infrastructure Leading to Diversity (BUILD) grant awards help undergraduate institutions implement and study ways to engage and retain students from diverse backgrounds in biomedical research. The program aims to help these students on the pathway to becoming scientists. Primary institutions eligible for BUILD awards have fewer than $7.5 million in total NIH research project grant funding and a student population with at least 25 percent Pell Grant recipients. BUILD is part of the Common Fund Diversity Program Consortium, a national collaborative dedicated to enhancing diversity in the biomedical research workforce.
  • Maximizing Access to Research Careers Undergraduate Student Training in Academic Research (MARC U-STAR) awards provide support for undergraduate trainees from underrepresented backgrounds to gain skills and improve their preparation for high-caliber graduate training at the doctoral level. Awards are made to colleges and universities that offer the baccalaureate degree.
  • The Research Initiative for Scientific Enhancement (RISE) program aims to help reduce the existing gap between underrepresented and well-represented students in completing doctoral degrees. RISE supports institutions that award the baccalaureate, master’s, or doctoral degree in biomedical science fields; programs include well-integrated developmental activities designed to strengthen students’ academic preparation, research training, and professional skills.

Although BUILD, MARC, and RISE offer a variety of activities at more than 100 supported institutions during the school year—including laboratory research opportunities, faculty mentoring, seminars, and workshops—the programs also provide training experiences throughout the summer. The slideshow below gives a quick peek into what several students participating in MARC, RISE, and BUILD activities did over the summer.

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Having a BLaST in Alaska … and Beyond

Lori Gildehaus and her lovable, mischievous dog, Charley. Credit: Lori Gildehaus.

Lori Gildehaus loves her job because she’s almost always doing something different. Some days, she leads professional development sessions for undergraduate students at the University of Alaska, Fairbanks (UAF). Other days, she’s weathered down in isolated communities along Alaska’s coast while leading community science and outreach events. These activities are just a few of her many responsibilities. Gildehaus is a laboratory research and teaching technician for UAF’s Biomedical Learning and Student Training Exit icon (BLaST) program.

UAF’s BLaST program is one of 10 sites across the country in the Building Infrastructure Leading to Diversity (BUILD) initiative. As a component of the NIH Diversity Program Consortium, BUILD aims to find the best ways to engage and retain students from diverse backgrounds in biomedical research. Each BUILD site is as unique as the community it serves. UAF’s BLaST program embraces Alaska Native culture and the unique landscape that its students, faculty, and staff call home.

UAF attracts students from across Alaska, making for a diverse student body. BLaST serves not only UAF but also seven other campuses throughout Alaska, ranging from IỊisaġvik College in Utqiaġvik (formerly Barrow) at the northern tip of the state, to the University of Alaska Southeast in Sitka, more than 1,000 miles away. In any area that large, it would be difficult to organize community science outreach and foster connections between institutions. But in Alaska, there aren’t even roads connecting most rural campuses to Fairbanks.

Bridging gaps

Gildehaus and BLaST’s four other laboratory research and teaching technicians help bridge these gaps and bring science to local communities. They also serve as intermediaries between undergraduate students doing research and their professors. For undergraduates, talking to professors can be intimidating, and navigating the university landscape can be overwhelming. One of Gildehaus’ responsibilities is providing guidance to students.

“We want undergraduates to have a really good opportunity to explore their interests and have a good experience on their research projects,” Gildehaus says.

Gildehaus has a broad background, including biological sciences, human anatomy and physiology, science outreach, and mentoring. This experience helps her develop BLaST’s mentoring component. BLaST uses a tiered mentoring approach to provide opportunities for undergraduate and graduate students to share experiences and participate in mentoring.

Gildehaus has planned three mentoring workshops for fall 2017. One of these workshops, organized with assistance from the National Research Mentoring Network Exit icon, will focus on culturally aware mentoring. Another will teach attendees how to navigate conversations, share stories, and increase awareness and understanding of Alaska Native and other cultures.

Bringing science outside the lab

BLaST’s diverse group of students includes many people who reside in rural areas and live a subsistence lifestyle. Traditional lab work schedules and science education can often seem disconnected from these communities. To better engage students, BLaST implements the One Health Approach, which emphasizes the interconnectedness between human, animal, and environmental health by promoting ways to expand interdisciplinary collaborations to attain optimal health for all. The program helps students recognize that there are opportunities to be involved in biomedical research in their communities, such as researching the natural vegetation of the Alaskan tundra, studying marine mammals, or finding cures for illnesses.   Continue reading

Fall 2017 Issue of Findings Magazine

It’s back! Check out the new issue of Findings magazine.

Findings presents cutting-edge research from scientists in diverse biomedical fields. The articles are aimed at high school students with the goal of making science—and the people who do it—interesting and exciting, and to inspire young readers to pursue careers in biomedical research. In addition to putting a face on science, Findings offers activities such as quizzes and crossword puzzles and, in its online version, video interviews with scientists.

The Fall 2017 issue profiles Yale University biologist Enrique De La Cruz, who studies how actin—a protein chain that supports cell structure—breaks so easily. Also profiled is University of California, Berkeley, biologist Rebecca Heald and her study of developmental factors that control an animal’s size.

This issue also features:

  • A virtual reality program designed to help burn patients manage pain
  • The promise of gene therapy for glaucoma
  • The many ways scientists categorize the biological world using “omics”
  • What researchers know—and don’t know—about how general anesthetics work
  • How animation helps researchers visualize interactions between biological molecules
  • How cells use sugary outer coatings to distinguish friend from foe
  • What makes our tissues stiff, squishy, solid, or see-through (hint: its initials are ECM)
  • How super-powerful microscopes are revealing views of biology never possible before

View Findings online, or order a print copy (classroom sets of up to 30 copies are available for educators).

 

Engage Students in Science with SEPA-Funded Education Materials

As school starts up again, we look forward to a year that further enhances health and science literacy and brings students closer to pursuing science as an exciting future career. The National Institutes of Health continues to help both educators and students toward these goals through its Science Education Partnership Award (SEPA) Program Exit icon.

What Is SEPA?

SEPA funds innovative science, technology, engineering, and mathematics (STEM), and informal science education (ISE) projects for students in pre-kindergarten through grade 12 (P-12), as well as public outreach activities such as science museum exhibits. Its goal is to invest in educational activities, including interactive online resources, that improve the training of a future workforce to meet the country’s biomedical research needs. SEPA encourages partnerships between biomedical researchers and P-12 teachers, schools, and other interested groups. SEPA provides:

  • Opportunities for students from underserved communities to learn about careers in basic or clinical research.
  • Professional development, skills, and knowledge building for science teachers.
  • Support for science centers and museum exhibits on health and medicine to improve community health literacy.

In March 2017, SEPA found its new home with the National Institute of General Medical Sciences (NIGMS). Congress mandated the move so that SEPA could more efficiently integrate with our other institution-building and research training programs and increase collaboration opportunities between them.

SEPA-Funded Resources

The following are just some of the various SEPA-funded resources that educators can use to engage their students in science:

Spiral of Life Mural Series: Animal Evolution Exit icon. Credit: Duquesne University.

The Partnership in Education: movies, games, and curricula Exit icon (elementary and middle school)

The Partnership in Education at Duquesne University specializes in using cutting-edge technologies and creative media platforms—including videos, apps, posters, and lesson plans—to bring science to life and inspire lifelong learning. Topics include development Exit icon, evolution Exit icon, the science of sleep, and regenerative medicine Exit icon. Continue reading

Happy Birthday, BioBeat

This month, our blog that highlights NIGMS-funded research turns four years old! For each candle, we thought we’d illuminate an aspect of the blog to offer you, our reader, an insider’s view.

Who are we?

Over the years, the editorial team has included onsite science writers, office interns, staff scientists and guest authors from universities. Kathryn, who’s a regular contributor, writes entirely from her home office. Chris, who has a Ph.D. in neuroscience and now manages the blog, used to do research in a lab. Alisa has worked in NIGMS’ Bethesda-based office the longest: 22 years! She and I remember when we first launched Biomedical Beat as an e-newsletter in 2005. You can read more about each of the writers on the contributors page and if you know someone who’s considering a career in science communications, tell them to drop us a line.

How do we come up with the stories?

We get our story ideas from a range of sources. For instance, newspaper articles about an experimental pest control strategy in Florida and California prompted us to write about NIGMS-funded studies exploring the basic science of the technique. A beautiful visual from a grantee’s institution inspired a short post on tissue regeneration research. And an ongoing conversation with NIGMS scientific staff about the important role of research organisms in biological studies sparked the idea for a playful profile of one such science superstar.

A big change in our storytelling has been shifting the focus from a single finding to broader progress in a lab or field. So instead of reporting on a study just published in a scientific journal, we may write about the scientist’s career path or showcase a collection of recent findings in that particular field. These approaches help us demonstrate that scientific understanding usually progresses through the slow and steady work undertaken by many labs.

What are our favorite posts?

I polled the writers on posts they liked, and the list is really long! Here are the top picks.


Four Ways Inheritance Is More Complex Than Mendel Knew


The Endoplasmic Reticulum: Networking in the Cell


Interview With a Scientist: Janet Iwasa, Molecular Animator


From Basic Research to Bioelectric Medicine


An Insider’s Look at Life: Magnified, an Airport Exhibit of Stunning Microscopy Images

What are your favorite posts?

We regularly review data about the number of times a blog post has been viewed to identify the ones that interest readers the most. That information also helps guide our decisions about other topics to feature on the blog. The Cool Image posts are among the most popular! Below are some other chart-topping posts.


Our Complicated Relationship With Viruses


The Proteasome: The Cells Trash Processor in Action


Demystifying General Anesthetics


Meet Sarkis Mazmanian and the Bacteria That Keep Us Healthy


5 Reasons Biologists Love Math

We always like hearing from readers! If there’s a basic biomedical research topic you’d like us to write about, or if you have feedback on a story or the blog in general, please leave your suggestions in the comment field below or email me.