Actin’s Many Roles

Skin cancer cells

Skin cancer cells from a mouse. Credit: Catherine and James Galbraith, Oregon Health and Science University, Center for Spatial Systems Biomedicine, Knight Cancer Institute.

This heart-shaped image shows two mouse skin cancer cells connected to each other with actin, a protein that is part of the cellular skeleton. Researchers use mouse cells like these to tease out the molecular methods that cancer uses to invade new tissues in the body. It turns out that actin plays an essential role.

Cells can move as a collective, or independently. Movement of an individual cell requires a series of carefully controlled steps. Among them, a cell must break contacts with its neighbor cells and change its connections to the proteins and fibers around it. In addition, it must sense and follow a chemical path through the tissue it lies in. To do this, a cell changes shape, molding its membrane into flaps or feet called protrusions reaching in the direction it is traveling. Actin, among a variety of other molecules, is involved in all of these steps, but especially the shape change, when it gathers inside the cell membrane to help form the protrusions. Continue reading

On Pi Day, Computational Biologists Share What They Love About Math

Another cool fact about Pi: The mirror reflection of the numbers 3 1 4 spells out P I E.

Why do math lovers around the world call March 14 “Pi Day”? Because Pi, the ratio of a circle’s circumference to its diameter, is 3.14. Pi is a Greek letter (π) that represents a constant in math: All circles have the same Pi, regardless of their size. Pi has been calculated out to as many as 1 trillion digits past the decimal, and it can continue forever without repetition or pattern.

In honor of Pi Day, we asked several biomedical researchers in the field of computational biology to tell us why they love math and how they use it in their research. Continue reading

Online Virus Tracking Tool Nextstrain Wins Inaugural Open Science Prize

Credit: Trevor Bedford and Richard Neher,

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.

Field Focus: High-Quality Genome Sequences Inform the Study of Human Evolution

Leafing through my favorite biology textbook from a handful of years ago, I was struck by the relative brevity of the chapter on human evolution. While other fields of biological research have enjoyed a steady gallop of productivity over the last few decades due in part to advances in computing power, imaging technology and experimental methods, the study of human evolution can be seen as having lagged behind until recently due to an almost complete dependence on fossil evidence.

Fortunately, contemporary biology textbook chapters on human evolution are being primed for a serious upgrade thanks to the recent availability of high-quality genome sequences from diverse modern human populations as well as from ancient humans and other non-human hominids, including the Neanderthals and Denisovans (but, for purposes of this story, not the Great Apes).

Modern human skull (left) and Neanderthal skull (right), shown to scale. There are not enough Denisovan bone fragments to reconstruct its skull. Credit: Wikimedia Commons, hairymuseummatt.

What are the new resources for studying human evolution?

The cost of DNA sequencing has dropped precipitously in the last decade. As a result, more complete human genome sequences become available for analysis with each passing year.

For example, the 1000 Genomes Project Exit icon includes more than 1,000 full human genome sequences of individuals from European, Asian, American and Sub-Saharan African populations. Earlier this year, the Simons Genome Diversity Project Exit icon further increased the number of available human genomes by adding 300 individuals representing 142 populations around the globe. Continue reading

Student Researcher Finds New Clues About Flu with Old Data

Do you like to find new uses for old things? Like weaving old shirts into a rug, repurposing bottles into candle holders or turning packing crates into tables? Katie Gostic, a University of California, Los Angeles (UCLA) graduate student, likes finding new uses for old data. She channeled this interest when she analyzed existing data to study whether childhood exposure to flu affects a person’s future immunity to the disease.

Katie Gostic
Gostic conducted research for the flu project during the summer of 2015 when she was visiting her boyfriend, a tropical biologist, in Alamos, Sonora, Mexico. Credit: Charlie de la Rosa.

As an undergraduate student at Princeton University, Gostic was originally pursuing a degree in engineering. Her focus shifted to biology after taking an infectious disease modeling class. Gostic’s background in math and programming allows her to take large, complex pre-existing data sets and reanalyze them using new tools and methods. The result: Information that wasn’t accessible when the data were first collected.

Now a graduate researcher in the ecology and evolutionary biology lab of James Lloyd-Smith Exit icon, Gostic studies infectious diseases. The lab builds mathematical models to investigate zoonotic diseases—diseases that animals can transmit to humans but that humans don’t frequently spread between each other. Examples include diseases caused by Leptospira, a type of bacteria that infects household pets and many other animals, and monkeypox, a virus whose transmission to humans is increasing since the eradication of smallpox. The lab also studies bird flus, a category of flu viruses that infect birds and other animals and only occasionally jump to people. A very small number of cases of human-to-human transmission of bird flus have been recorded. However, if a bird flu virus mutated in a way that allowed it to spread among humans, it could cause a pandemic. Continue reading

On this Darwin Day, Evolutionary Geneticist Dr. Dan Janes Discusses the Scientific Contributions of Charles Darwin

This Sunday, February 12, is Darwin Day—an occasion to recognize the scientific contributions of 19th-century naturalist Charles Darwin. In this video (originally posted on Darwin Day 2016), our own evolutionary geneticist, Dan Janes, answers questions about Darwin and the role of evolution in health and biomedicine.

Continue reading

Not Discounting His Future: Austin Works Toward His Goals

This is the second post in a new series highlighting NIGMS’ efforts toward developing a robust, diverse and well-trained scientific workforce.

Austin Phanouvong
Credit: Christa Reynolds.
Austin Phanouvong
Academic Institution: Portland State University
Major: Biology
Minor: Chemistry
Mentor: Suzanne Mitchell
Favorite Book: The Alchemist, by Paulo Coelho
Favorite Food: Sushi
Hobbies: Hiking, cooking and traveling

BUILD and the Diversity Program Consortium

The Diversity Program Consortium (DPC) aims to enhance diversity in the biomedical research workforce through improved recruitment, training and mentoring nationwide. It comprises three integrated programs—Building Infrastructure Leading to Diversity (BUILD), which implements activities at student, faculty and institutional levels; the National Research Mentoring Network (NRMN), which provides mentoring and career development opportunities for scientists at all levels; and the Coordination and Evaluation Center (CEC), which is responsible for evaluating and coordinating DPC activities.

Ten undergraduate institutions across the United States have received BUILD grants, and together, they serve a diverse population. Each BUILD site has developed a unique program intended to engage and prepare students for success in the biomedical sciences and maximize opportunities for research training and faculty development. BUILD programs include everything from curricular redesign, lab renovations, faculty training and research grants, to student career development, mentoring and research-intensive summer programs.

Austin Phanouvong, 21, likes biology because it teaches him about life.

“Even the way we walk, the way we breathe – there’s all these little components to it that we don’t even think about but they’re very helpful, and one hiccup in that system can lead to many diseases and sicknesses,” Phanouvong says.

Born and raised in Portland, Oregon, Phanouvong is a senior at Portland State University (PSU), where he is in the Building Infrastructure Leading to Diversity (BUILD) EXITO program. As a student in BUILD EXITO Exit icon (which stands for “Enhancing Cross-Disciplinary Infrastructure and Training at Oregon”), Phanouvong takes biomedical science courses, conducts research and participates in professional development workshops and seminars. He has learned about preparing a CV and writing personal statements. In spring 2017, Phanouvong will graduate with a major in biology and a minor in chemistry. He will continue to pursue research opportunities as he applies for medical school, and he hasn’t ruled out the possibility of pursuing a Ph.D. in the future.

Since high school, Phanouvong’s desire has been to help people through a healthcare career. Originally, he was interested in nursing, but he decided he could push his career plans and education farther by going to medical school. Because of his interest in hands-on research, last year Phanouvong’s honors thesis advisor recommended he apply for the BUILD program, and Phanouvong realized BUILD EXITO would be a great opportunity to engage in research as an undergraduate student. Continue reading

Cool Image: Inside a Biofilm Build-up

A growing Vibrio cholerae biofilm.

A growing Vibrio cholerae biofilm. Each slightly curved comma shape represents an individual bacterium from assembled confocal microscopy images. Different colors show each bacterium’s position in the biofilm in relation to the surface on which the film is growing. Credit: Jing Yan, Ph.D., and Bonnie Bassler, Ph.D., Department of Molecular Biology, Princeton University, Princeton, NJ.

Bacteria use many methods to overcome threats in their environment. One of these ways is forming colonies called biofilms on surfaces of objects. Often appearing like the bubble-shaped fortress represented in this image, biofilms enable bacteria to withstand attacks, compete for space and survive fluctuations in nutrient supply. Bacteria aggregated within biofilms inside our bodies, for example, resist antibiotic therapy more effectively than free swimming cells, making infections difficult to treat. On the other hand, biofilms are also useful for making microbial fuel cells and for waste-water treatment. Learning how biofilms work, therefore, could provide essential tools in our ongoing battle against disease-causing agents and in our efforts to harness beneficial bacterial behaviors. Researchers are now using new imaging techniques to watch how biofilms grow, cell by cell, and to identify more effective ways of disrupting or fostering them.

Until now, poor imaging resolution meant that scientists could not see what individual bacteria in the films are up to as the biofilms grow. The issue is that bacteria are tiny, making imaging each cell, as well as the ability to distinguish each cell in the biofilm community, problematic. Continue reading

Cool Tools: Pushing the Limits of High-Resolution Microscopy

Cell biologists would love to shrink themselves down and actually see, touch and hear the inner workings of cells. Because that’s impossible, they have developed an ever-growing collection of microscopes to study cellular innards from the outside. Using these powerful tools, researchers can exhaustively inventory the molecular bits and pieces that make up cells, eavesdrop on cellular communication and spy on cells as they adapt to changing environments.

In recent years, scientists have developed new cellular imaging techniques that allow them to visualize samples in ways and at levels of detail never before possible. Many of these techniques build upon the power of electron microscopy (EM) to see ever smaller details.

Unlike traditional light microscopy, EM uses electrons, not light, to create an image. To do so, EM accelerates electrons in a vacuum, shoots them out of an electron gun and focuses them with doughnut-shaped magnets onto a sample. When electrons bombard the sample, some pass though without being absorbed while others are scattered. The transmitted electrons land on a detector and produce an image, just as light strikes a detector (or film) in a camera to create a photograph.

This image, showing a single protein molecule, is a montage. It was created to demonstrate how dramatically cryo-EM has improved in recent years. In the past, cryo-EM was only able to obtain a blobby approximation of a molecule’s shape, like that shown on the far left. Now, the technique yields exquisitely detailed images in which individual atoms are nearly visible (far right). Color is artificially applied. Credit: Veronica Falconieri, Subramaniam Lab, National Cancer Institute.

Transmission electron microscopes can magnify objects more than 10 million times, enabling scientists to see the outline and some details of cells, viruses and even some large molecules. A relatively new form of transmission electron microscopy called cryo-EM enables scientists to view specimens in their natural or near-natural state without the need for dyes or stains.

In cryo-EM—the prefix cry- means “cold” or “freezing”—scientists freeze a biological sample so rapidly that water molecules do not have time to form ice crystals, which could shove cellular materials out of their normal place. Cold samples are more stable and can be imaged many times over, allowing researchers to iteratively refine the image, remove artifacts and produce even sharper images than ever before. Continue reading

Interview With a Scientist: Thomas O’Halloran, Metal Maestro

Inside our bodies is a surprising amount of metal. Not enough to set off the scanners at the airport or make us rich, but enough to fill each of our cells with billions of metal ions, including calcium, iron, copper and zinc. These ions facilitate critical biological functions.

However, too much of any metal can be toxic, while too little can cause disease. Our cells carefully monitor and control their metal content using a whole series of proteins that bind, sense and transport metal ions.

Keeping tabs on why and how metals flow into and out of our cells is a passion of Thomas O’Halloran Exit icon, professor of chemistry and molecular biosciences at Northwestern University in Illinois. For the past three decades, O’Halloran has investigated how fluctuations in the amount of metal ions inside cells influence gene expression, cell growth and other vital functions. Using a variety of approaches, he has uncovered new types of proteins that bind metal ions and investigated the role that imbalances in these ions play in a number of disease-related physiological processes.

One recent focus of his studies has been how zinc regulates oocyte (egg cell) maturation and fertilization. Ultimately, his work could help us better understand infertility, cancer and certain bacterial infections.