Computational Biologist Melissa Wilson on Sex Chromosomes, Gila Monsters, and Career Advice

Melissa Wilson wearing a floral dress and speaking beside a podium during her lecture. Dr. Melissa Wilson.
Credit: Chia-Chi Charlie Chang.

The X and Y chromosomes, also known as sex chromosomes, differ greatly from each other. But in two regions, they are practically identical, said Melissa Wilson Link to external web site, assistant professor of genomics, evolution, and bioinformatics at Arizona State University.

“We’re interested in studying how the process of evolution shaped the X and the Y chromosome in gene content and expression and how that subsequently affects literally everything else that comes with being a human,” she said at the April 10 NIGMS Director’s Early-Career Investigator (ECI) Lecture at NIH.

Continue reading “Computational Biologist Melissa Wilson on Sex Chromosomes, Gila Monsters, and Career Advice”

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

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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Online Virus Tracking Tool Nextstrain Wins Inaugural Open Science Prize

Nextstrain’s analysis of the genomes from Zika virus obtained in 25 countries over the past few years.

Credit: Trevor Bedford and Richard Neher, nextstrain.org.

Over the past decade, scientists and clinicians have eagerly deposited their burgeoning biomedical data into publicly accessible databases. However, a lack of computational tools for sharing and synthesizing the data has prevented this wealth of information from being fully utilized.

In an attempt to unleash the power of open-access data, the National Institutes of Health, in collaboration with the Howard Hughes Medical Institute and Britain’s Wellcome Trust, launched the Open Science Prize Exit icon. Last week, after a multi-stage public voting process, the inaugural award was announced. The winner of the grand prize—and $230,000—is a prototype computational tool called nextstrain Exit icon that tracks the spread of emerging viruses such as Ebola and Zika. This tool could be especially valuable in revealing the transmission patterns and geographic spread of new outbreaks before vaccines are available, such as during the 2013-2016 Ebola epidemic and the current Zika epidemic.

An international team of scientists—led by NIGMS grantee Trevor Bedford Exit icon of the Fred Hutchinson Cancer Research Center, Seattle, and Richard Neher Exit icon of Biozentrum at the University of Basel, Switzerland—developed nextstrain as an open-access system capable of sharing and analyzing viral genomes. The system mines viral genome sequence data that researchers have made publicly available online. nextstrain then rapidly determines the evolutionary relationships among all the viruses in its database and displays the results of its analyses on an interactive public website.

The image here shows nextstrain’s analysis of the genomes from Zika virus obtained in 25 countries over the past few years. Plotting the relatedness of these viral strains on a timeline provides investigators a sense of how the virus has spread and evolved, and which strains are genetically similar. Researchers can upload genome sequences of newly discovered viral strains—in this case Zika—and find out in short order how their new strain relates to previously discovered strains, which could potentially impact treatment decisions.

Nearly 100 interdisciplinary teams comprising 450 innovators from 45 nations competed for the Open Science Prize. More than 3,500 people from six continents voted online for the winner. Other finalists for the prize focused on brain maps Exit icon, gene discovery Exit icon, air-quality monitoring Exit icon, neuroimaging Exit icon and drug discovery Exit icon.

nextstrain was funded in part by NIH under grant U54GM111274.

There’s an “Ome” for That

In the 13 years since the sequencing of the human genome, the list of “omes” has proliferated. Drop us a comment with your favorite ome—we may feature it in a follow-up post next month.

Have you ever collected coins, cards, toy trains, stuffed animals? Did you feel the need to complete the set? If so, then you may be a completist. A completist will go to great lengths to acquire a complete set of something.

Scientists can also be completists who are inspired to identify and catalog every object in a particular field to further our understanding of it. For example, a comprehensive parts list of the human body—and of other organisms that are important in biomedical research—could aid in the development of novel treatments for diseases in the same way that a parts list for a car enables auto mechanics to build or repair a vehicle.

More than 15 years ago, scientists figured out how to catalog every gene in the human body. In the years since, rapid advances in technology and computational tools have allowed researchers to begin to categorize numerous aspects of the biological world. There’s actually a special way to name these collections: Add “ome” to the end of the class of objects being compiled. So, the complete set of genes in the body is called the “genome,” and the complete set of proteins is called the “proteome.”

Below are three -omes that NIH-funded scientists work with to understand human health.

Genome

Illustration of the entire outer shell of the bacteriophage MS2. Credit: Wikimedia Commons, Naranson.

The genome is the original -ome. In 1976, Belgium scientists identified all 3,569 DNA bases—the As, Cs, Gs and Ts that make up DNA’s code—in the genes of bacteriophage MS2, immortalizing this bacteria-infecting virus as possessing the first fully sequenced genome.

Over the next two decades, a small handful of additional genomes from other microorganisms followed. The first animal genome was completed in 1998. Just 5 years later, scientists identified all 3.2 billion DNA bases in the human genome, representing the work of more than 1,000 researchers from six countries over a period of 13 years. Continue reading “There’s an “Ome” for That”

Exploring the Evolution of Spider Venom to Improve Human Health

Brown recluse

Female brown recluse spider. Credit Matt Bertone, North Carolina State University.

This Halloween, you’re not likely to see many trick-or-treaters dressed as spiders. Google Trends pegs “Spider” as the 87th most searched-for Halloween costume, right between “Hippie” and “The Renaissance.” But don’t let your guard down. Spiders are everywhere.

“I grew up on a farm in Indiana and had the luxury of exploring and turning over rocks and being curious. Any feelings of being grossed out by spiders were rapidly replaced by my feelings of awe for how amazing and diverse these creatures are.”– Greta Binford”

More than 46,000 species of spiders creepy crawl across the globe, on every continent except Antarctica. Each species produces a venom composed of an average of 500 distinct toxins, putting the conservative estimate of unique venom compounds at more than 22 million. This staggering diversity of venoms, collectively referred to as the venome, has only begun to be explored. Continue reading “Exploring the Evolution of Spider Venom to Improve Human Health”