Emily Carlson

About Emily Carlson

Emily, who edits this blog and the Inside Life Science article series, writes about a wide range of NIGMS-funded research and NIGMS policies. One of her goals is to help people better understand and appreciate basic research and the NIH role in funding it.

Raking the Family Tree for Disease-Causing Variations

Silhouettes of people with nucleic acid sequences and a stethoscope.
A new software tool analyzes disease-causing genetic variations within a family. Credit: NIH’s National Human Genome Research Institute.

Changes in your DNA sequence occur randomly and rarely. But when they do happen, they can increase your risk of developing common, complex diseases, such as cancer. One way to identify disease-causing variations is to study the genomes of family members, since the changes typically are passed down to subsequent generations.

To rake through a family tree for genetic variations with the highest probabilities of causing a disease, researchers combined several commonly-used statistical methods into a new software tool called pVAAST. The scientific team, which included Mark Yandell and Lynn Jorde of the University of Utah and Chad Huff of the University of Texas MD Anderson Cancer Center, used the tool to identify the genetic causes of a chronic intestinal inflammation disease and of developmental defects affecting the heart, face and limbs.

The results confirmed previously identified genetic variations for the developmental diseases and pinpointed a previously unknown variation for the intestinal inflammation. Together, the findings confirm the ability of the tool to detect disease-causing genetic changes within a family. Another research team has already used the software tool to discover rare genetic changes associated with family cases of breast cancer. These studies are likely just the beginning for studying genetic patterns of diseases than run in a family.

This work also was funded by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute; National Human Genome Research Institute; National Heart, Lung, and Blood Institute; and National Institute of Mental Health.

Learn more:
University of Utah News Release Exit icon
Yandell Exit icon, Jorde Exit icon and Huff Exit icon Labs

New Compound Improves Insulin Levels in Preliminary Studies

compound
A new compound (chemical structure shown here) blocks the activity of an enzyme involved in glucose regulation.

The discovery of a compound that slows the natural degradation of insulin in mice opens up a new area of investigation in the search for drugs to treat diabetes. The research team, which included David Liu Exit icon and Alan Saghatelian Exit icon of Harvard University, Markus Seeliger Exit icon of Stony Brook University School of Medicine, and Wei-Jen Tang Exit icon of the University of Chicago focused on insulin-degrading enzyme, or IDE. Using a method called DNA-templated synthesis, the scientists made 14,000 small molecules and found one that bound to the enzyme, suggesting it might modulate the enzyme’s activity. Work in test tubes and in animal models confirmed this—and showed that blocking IDE activity improved insulin levels and glucose tolerance. The researchers also learned that the enzyme is misnamed: In addition to insulin, it degrades two other hormones involved in glucose regulation.

NIGMS’ Peter Preusch says, “This is a very interesting fusion of chemical methods and biology that has uncovered new basic science findings about insulin processing with potential clinical impact.”

This work also was funded by NIH’s National Cancer Institute and the Office of the Director.

Learn more:
Harvard University News Article Exit icon
Chemistry of Health Booklet

Revealing the Human Proteome

An artistic interpretation of the human proteome. Credit: Corinne Sandone and Jennifer Fairman, Johns Hopkins University.
An artistic interpretation of the human proteome. Credit: Corinne Sandone and Jennifer Fairman, Johns Hopkins University.

Genes control the most basic functions of the cell, including what proteins to make and when. In 2003, the Human Genome Project created a draft map of our genes, and now researchers have completed a draft map of the human proteome—the set of all our proteins. The map, which includes proteins encoded by more than 17,000 genes as well as ones from regions of the genome previously thought to be non-coding, will help advance a broad range of research into human health and disease.

Read more about the proteome map in this NIH Research Matters article.

Knowing Networks

Artist's rendition of a network diagram. Credit: Allison Kudla, Institute for Systems Biology.
Artist’s rendition of a network diagram. Credit: Allison Kudla, Institute for Systems Biology.

Networks—both real and virtual—are everywhere, from our social media circles to the power grid that delivers electricity. The interactions of genes, proteins and other molecules in a cell are examples of networks, too.

Scientists working in a field called systems biology study and chart living networks to learn how the individual parts work together to make a functioning whole and what happens when these complex, dynamic systems go awry. For example, the network diagram here depicts yeast cells (superimposed circles) and the biochemical “chatter” between them (lines) that tells the cells to gather together in clumps. This clumping helps them survive stressful conditions like a shortage of nutrients.

Network diagrams provide more than just hub-and-spoke pictures. They can yield information that helps us better understand—and potentially influence—complex phenomena that affect our health.

Read more about network analysis and systems biology in this Inside Life Science article.

How Cells Take Out the Trash

Proteins entering the proteasome. Credit: Office of Biological and Environmental Research of the U.S. Department of Energy Office of Science.
When proteins enter the proteasome, they’re chopped into bits for re-use. Credit: Office of Biological and Environmental Research of the U.S. Department of Energy Office of Science.

As people around the world mark Earth Day (April 22) with activities that protect the planet, our cells are busy safeguarding their own environment.

To keep themselves neat, tidy and above all healthy, cells rely on a variety of recycling and trash removal systems. If it weren’t for these systems, cells could look like microscopic junkyards—and worse, they might not function properly. Scientists funded by the National Institutes of Health are therefore working to understand the cell’s janitorial services to find ways to combat malfunctions.

Read more about how cells take out the trash and handle recycling in this Inside Life Science article.

Basic Research Fuels Medical Advances

Genetic defect that causes myotonic dystrophy type 2 and used that information to design drug candidates to counteract the disease. Credit: Ilyas Yildirim, Northwestern University.
Scientists revealed a detailed image of the genetic change that causes myotonic dystrophy type 2 and used that information to design drug candidates to counteract the disease. Credit: Ilyas Yildirim, Northwestern University. View larger image

This image may look complicated, but it tells a fairly straightforward tale about basic research: Learning more about basic life processes can pave the way for medical and other advances.

In this example, researchers led by Matthew Disney of the Scripps Research Institute’s Florida campus focused on better understanding the structural underpinnings of myotonic dystrophy type 2, a relatively rare, inherited form of adult-onset muscular dystrophy. While this work is still in the preliminary stages, it may hold potential for someday treating the disorder.

Some 300,000 NIH-funded scientists are working on projects aimed at improving disease diagnosis, treatment and prevention, often through increasing understanding of basic life processes.

Read the complete Inside Life Science article.

Meet Jeff Shaman

Jeff Shaman
Jeff Shaman
Field: Climatology
Works at: Columbia University’s Mailman School of Public Health, N.Y.
Favorite high school subject: Biology
First job: Guide at the Franklin Institute in Philadelphia, Pa.
Alternative career: Opera singer
Credit: Anne Foulke

Before he wrote any scientific papers, Jeff Shaman wrote operas. At the premiere of one of his operas, an 80-minute story about psychoanalysis, reviewers said the work “crackle[d] with invention.”

After 4 years of training to become an opera singer, Shaman realized that the work wouldn’t offer him career stability. He started thinking about his other interests. After college, where he majored in biology with a focus on ecology, he had volunteered to help with HIV clinical trials and developed a fascination with understanding infectious diseases. He wondered if the quantitative tools and methods used to study the physical sciences—another interest area—could inform how contagions spread and possibly even lead to systems for monitoring or predicting their transmission.

So Shaman returned to school—this time, for advanced degrees in earth and environmental sciences. He now studies the relationship between soil wetness and mosquito-borne diseases such as malaria in Africa and West Nile in Florida.

“I love science—probing questions, thinking about problems, finding solutions, pursuing my ideas,” says Shaman.

His Findings

A few years ago, Shaman took some of his scientific compositions in another direction by focusing on seasonal flu outbreaks. For more than 60 years, researchers have linked seasonal flu outbreaks with environmental data like humidity and temperature. Shaman analyzed this work and figured out that absolute humidity, rather than relative humidity, was the best predictor of outbreaks. Now he’s applied state-of-the-art mathematical modeling and real-time observational estimates of influenza incidence to predict when outbreaks will likely occur.

His forecasting technique mimics that used by meteorologists to predict weather conditions like temperatures, precipitation and even hurricane landfall. Shaman’s version incorporates variables like how transmissible a virus is, the number of days people are contagious and sick, and how much humidity is in the air.

The flu forecasts build on a series of studies in which Shaman and his colleagues used data from previous influenza seasons to test their predictions and improve reliability of their model. The work culminated with real-time predictions for 108 cities during the 2012-2013 influenza season. The forecasts could reliably estimate the peaks of flu outbreaks up to 9 weeks before they occurred.

For the 2013-2014 flu season, the researchers continued to make weekly predictions. But instead of first publishing the results in a scientific journal, they posted them on a newly launched influenza forecasts Web site Exit icon where the public could view the projections.

“People understand the limitations and capabilities of weather forecasts,” says Shaman. “Our hope is that people will develop a similar familiarity with the flu forecasts and use that information to make sensible decisions.” For instance, the prediction of high influenza activity may motivate them to get vaccinated and practice other flu-prevention measures.

As he waits for the start of the next flu season, Shaman continues to tweak his forecast system to improve its reliability. He’s also beginning to address other questions, such as how to predict multiple outbreaks of different influenza strains and how to predict the spread of other respiratory illnesses.

Learn more:
Influenza Forecasts Web Site Exit icon
Forecasting Flu Article from Inside Life Science
What Drives Seasonal Flu Patterns? Article and Podcast from Inside Life Science

What Students Want to Know About Cells

Cell Day 2014

During a live online chat dubbed “Cell Day,” scientists at NIGMS recently fielded questions about the cell and careers in research from middle and high school students across the country. Here’s a sampling of the questions and answers, some of which have been edited for clarity or length.

What color are cells?
While cells with lots of iron, like red blood cells, may be red, usually cells are colorless.

How many different types of cells can be found inside the human body?
There are about 200 cell types and a few trillion total cells in the human body. That does not include bacteria, fungi and mites that live on the body.

Is it possible to have too many or not enough cells?
The answer depends on cell type. For example, within the immune system, there are many examples of diseases that are caused by too many or not enough cells. When too many immune cells accumulate, patients get very large spleens and lymph nodes. When too few immune cells develop, patients have difficulty fighting infections.

How fast does it take for a cell to produce two daughter cells?
Some cells, for example bacterial ones, can produce daughter cells very fast when nutrients are available. The doubling time for E. coli bacteria is 20 minutes. Other cells in the human body take hours or days or even years to divide.

Do skin cells stretch or multiply when you gain weight?
The size of cells is tightly regulated and maintained so they do not stretch much. As the surface area of the body increases with weight gain, the number of skin cells increases.

Why do cells self-destruct?
The term for cellular self-destruction is “apoptosis” or “programmed cell death.” Apoptosis is very important for normal development of humans and other animals as it ensures that we do not have too many cells and that “unhealthy” cells can be eliminated without causing harm to the surrounding cells. For instance, did you know that human embryos have webbing between their fingers and toes (just like ducks!)? Apoptosis eliminates the cells that form the web so that you are born with toes and fingers.

In what field is there a need for new scientists?
I would say that there is a need for scientists who can work at the interface between the biological and biomedical sciences and the data sciences. Knowing sophisticated mathematics and having computer skills to address questions like ‘what does this biomedical data tell us about particular diseases’ is still a challenge.

What is a scientist’s daily work day like? Is all of your time spent in a lab testing or like in an office throwing ideas around?
There are lots of different kinds of jobs a scientist can have. Many work in labs where they get to do experiments AND throw ideas around. Working in a lab is a lot of fun—you learn things about the world that no one has known before (how cool is that?). Other important jobs that scientists can do include writing about science as a journalist, helping other scientists patent new technologies they invent as a patent agent or lawyer, or working on important scientific policy issues for the government or other organizations.

Read more questions and answers

Capitalizing on Cellular Conversations

Fat cells
Fat cells such as these listen for incoming signals like FGF21, which tells them to burn more fat. Credit: David Gregory and Debbie Marshall. All rights reserved by Wellcome Images.

Living things are chatty creatures. Even when they’re not making actual sounds, organisms constantly communicate using chemical signals that course through their systems. In multicellular organisms like people, brain cells might call, “I’m in trouble!” signaling others to help mount a protective response. Single-celled organisms like bacteria may broadcast, “We have to stick together to survive!” so they can coordinate certain activities that they can’t carry out solo. In addition to sending out signals, cells have to receive information. To help them do this, they use molecular “ears” called receptors on their surfaces. When a chemical messenger attaches to a receptor, it tells the cell what’s going on and causes a response.

Scientists are following the dialogue, learning how cell signals affect health and disease. They’re also starting to take part in the cellular conversations, inserting their own comments with the goal of developing therapies that set a diseased system right.

Continue reading this new Inside Life Science article

Resetting Our Clocks: New Details About How the Body Tells Time

VIP in time-keeping brain cells
Boosting doses of a molecule called VIP (green) in time-keeping brain cells (blue) helped mice adjust quickly to major shifts in light-dark cycles. Credit: Cristina Mazuski in the lab of Erik Herzog, Washington University in St. Louis.

Springing clocks forward by an hour this Sunday, traveling across time zones, staring at a computer screen late at night or working the third shift are just a few examples of activities that can disrupt our daily, or circadian, rhythms. These roughly 24-hour cycles influence our physiology and behavior, and they’re driven by our body’s network of tiny timekeepers. If our daily routines fall out of sync with our body clocks, sleep, metabolic and other disorders can result.

Researchers funded by the National Institutes of Health have spent decades piecing together the molecular mechanisms of our biological clocks. Now, they’re building on that basic knowledge to better understand the intricate relationship among these clocks, circadian rhythms and physiology—and ultimately, find ways to manipulate the moving parts to improve our modern-day lives.

Continue reading this new Inside Life Science article