Interview with a Scientist: Michael Summers, Using Nuclear Magnetic Resonance to Study HIV

For more than 30 years, NIGMS has supported the structural characterization of human immunodeficiency virus (HIV) enzymes and viral proteins. This support has been instrumental in the development of crucial drugs for antiretroviral therapy such as protease inhibitors. NIGMS continues to support further characterization of viral proteins as well as cellular and viral complexes. These complexes represent the fundamental interactions between the virus and its host target cell and, as such, represent potential new targets for therapeutic development.

In this third in a series of three video interviews with NIGMS-funded researchers probing the structure of HIV, Michael Summers,Link to external web site professor of biochemistry at the University of Maryland, Baltimore County, discusses his use of nuclear magnetic resonance (NMR) technology to study HIV. Of recent interest to Summers has been using NMR to investigate how HIV’s RNA enables the virus to reproduce. His goals for this line of research are to develop treatments against HIV as well as learning how to best engineer viruses to deliver helpful therapies to individuals with a variety of diseases.

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Interview with a Scientist: Wes Sundquist, How the Host Immune System Fights HIV

For more than 30 years, NIGMS has supported the structural characterization of human immunodeficiency virus (HIV) enzymes and viral proteins. This support has been instrumental in the development of crucial drugs for antiretroviral therapy such as protease inhibitors. NIGMS continues to support further characterization of viral proteins as well as cellular and viral complexes. These complexes represent the fundamental interactions between the virus and its host target cell and, as such, represent potential new targets for therapeutic development.

In this second in a series of three video interviews with NIGMS-funded researchers probing the structure of HIV, Wes Sundquist,Link to external web site professor of biochemistry at the University of Utah, discusses his lab’s studies of how HIV uses factors in host cells to replicate itself. In particular, Sundquist focuses on the ESCORT pathway that enables HIV to leave infected cells and spread infection elsewhere.

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Interview With a Scientist: Irwin Chaiken, Rendering HIV Inert

For more than 30 years, NIGMS has supported the structural characterization of human immunodeficiency virus (HIV) enzymes and viral proteins. This support has been instrumental in the development of crucial drugs for antiretroviral therapy such as protease inhibitors. NIGMS continues to support further characterization of viral proteins as well as cellular and viral complexes. These complexes represent the fundamental interactions between the virus and its host target cell and, as such, represent potential new targets for therapeutic development.

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Interview with a Scientist: Jeramiah Smith on the Genomic Antics of an Ancient Vertebrate

The first known descriptions of cancer come from ancient Egypt more than 3,500 years ago. Early physicians attributed the disease to several factors, including an imbalance in the body’s humoral fluids, trauma, and parasites. Only in the past 50 years or so have we figured out that mutations in critical genes are often the trigger. The sea lamprey, a slimy, snake-like blood sucker, is proving to be an ideal tool for understanding these mutations.

The sea lamprey, often called the jawless fish, is an ancient vertebrate whose ancestor diverged from the other vertebrate lineages (fish, reptiles, birds and mammals) more than 500 million years ago. Jeramiah Smith,Link to external web site associate professor of biology at the University of Kentucky, has discovered that lamprey have two separate genomes: a complete genome specific to their reproductive cells, consisting of 99 chromosomes (humans have 23 pairs) and another genome in which about 20 percent of genes have been deleted after development. Using the lamprey model, Smith and his colleagues have learned that many of these deleted genes—such as those that initiate growth pathways—are similar to human oncogenes (i.e., cancer-causing genes).

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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.

Click on an image below to launch slideshow.

  • Zahraa Alhabib
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