Genetic Discovery Could Enable More Precise Prescriptions

Prescription pad with DNA illustration on it. Credit: Jane Ades, NIH’s National Human Genome Research Institute.
New insight into the genes that affect drug responses may help doctors prescribe the medications and doses best suited for each individual. Credit: Jane Ades, NIH’s National Human Genome Research Institute.

Scientists know that variations in certain genes can affect the way a person responds to medications. New research by Wolfgang Sadee Exit icon at Ohio State University shows that drug responses also depend on previously overlooked parts of DNA—sections that regulate genes, but are not considered genes themselves. This study focused on an important enzyme abbreviated CYP2D6 that processes about one-fourth of all prescription drugs. Differences in the enzyme’s performance, which range from zilch to ultra-rapid, can dramatically alter the effectiveness and safety of certain medications. Researchers discovered two new genetic variants that impact CYP2D6 performance. One of these, located in a non-gene, regulatory region of DNA, doubles or even quadruples enzyme activity. Coupling these findings with genetic tests could help doctors better identify each patient’s CYP2D6 activity level, enabling more precise prescriptions. The findings also open up a whole new area of investigation into genetic factors that impact drug response.

This work also was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Learn more:

Ohio State University News Release (no longer available)
Using Genes to Guide Prescriptions Article from Inside Life Science Series

Healing Wounds, Growing Hair

Wound healing in process. Credit: Yaron Fuchs and Samara Brown in the lab of Hermann Steller, Rockefeller University.

Credit: Yaron Fuchs and Samara Brown in the lab of Hermann Steller, Rockefeller University.

Whether injured by a scrape, minor burn or knife wound, skin goes through the same steps to heal itself. Regrowing hair over new skin is one of the final steps. All the hair you can see on your body is non-living, made up of “dead” cells and protein. It sprouts from living cells in the skin called hair follicle stem cells, shown here in red and orange. For more pictures of hair follicle stem cells—and many other stunning scientific images and videos—go to the NIGMS Image and Video Gallery.

Learn more:

Rockefeller University News Release Exit icon
Steller Lab Exit icon

Cell Biology Advances and Computational Techniques Earn Nobels for NIGMS Grantees

The winners of the 2013 Nobel Prize in physiology or medicine discovered that cells import and export materials using fluid-filled sacs called vesicles. Credit: Judith Stoffer.
The winners of the 2013 Nobel Prize in physiology or medicine discovered that cells import and export materials using fluid-filled sacs called vesicles. Credit: Judith Stoffer.

Every October, a few scientists receive a call from Sweden that changes their lives. From that day forward, they will be known as Nobel laureates. This year, five of the new Nobelists have received funding from NIGMS.

In physiology or medicine, NIGMS grantees James Rothman (Yale University) and Randy Schekman (University of California, Berkeley) were honored “for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells.” They share the prize with Thomas C. Südhof of Stanford University.

Rothman and Schekman started out working separately and in different systems—Schekman in yeast and Rothman in reconstituted mammalian cells—and their conclusions validated each others’. It’s yet another example of the power of investigator-initiated research and the value of model systems.

Highly accurate molecular models like this one are based on computational techniques developed by the winners of the 2013 Nobel Prize in chemistry. Credit: Rommie E. Amaro, University of California, San Diego.
Highly accurate molecular models like this one are based on computational techniques developed by the winners of the 2013 Nobel Prize in chemistry. Credit: Rommie E. Amaro, University of California, San Diego.

The three Nobelists in chemistry are NIGMS grantees Martin Karplus (Harvard University), Michael Levitt (Stanford University) and Arieh Warshel (University of Southern California), who developed “multiscale models for complex chemical systems.” They used computational techniques to obtain, for the first time, detailed structural information about proteins and other large molecules. Because of that work, scientists around the world are now able to access, with a few keystrokes, highly accurate models of nearly 100,000 molecular structures. Studying these structures has advanced our understanding of countless diseases, pharmaceuticals and basic biological processes.

Learn more:

NIGMS Nobel Prize News Announcement
NIGMS Nobelists Fact Sheet
Crossword Puzzle: Test Your Nobel Knowledge | Accessible Version

Cool Video: How Bee Venom Toxin Kills Cells

Credit: Huey Huang, Rice University.

Credit: Huey Huang, Rice University.

A new video, starring the toxin in bee venom, might help scientists design new drugs to combat bacterial infections. The video, by Rice University biophysicist Huey Huang Exit icon, condenses 6.5 minutes into less than a minute to show how the toxin, called melittin, destroys an animal or bacterial cell.

What looks like a red balloon is an artificial cell filled with red dye. Melittin molecules are colored green and float on the cell’s surface like twigs on a pond. As melittin accumulates on the cell’s membrane, the membrane expands to accommodate it. In the video, the membrane stretches into a column on the left.

When melittin levels reach a critical threshold, countless pinhole leaks burst open in the membrane. The cell’s vital fluids—red dye in the video—leak out through these pores. Within minutes, the cell collapses.

Many organisms use such a pore-forming technique to kill attacking bacterial cells. This research reveals molecular-level details of the strategy, bringing pharmaceutical scientists a step closer to harnessing it in the design of new antibiotics.

Learn more:

Rice University News Release Exit icon

Chemist Phil Baran Joins “Genius” Ranks as MacArthur Fellow

Cake decorated with a two-dimensional structure of the molecule, stephacidin B
When Baran’s research team succeeds in synthesizing an important natural product, the group sometimes celebrates with a cake decorated with a two-dimensional structure of the molecule. This molecule, stephacidin B, was isolated from a fungus and has anticancer properties. See images of other Baran lab cakes Exit icon.

As a newly appointed MacArthur Fellow, Phil Baran Exit icon is now officially a genius. The MacArthur award recognizes “exceptionally creative” individuals who have made significant contributions to their field and are expected to continue doing so. Baran, a synthetic organic chemist at Scripps Research Institute in La Jolla, Calif., was recognized today for “inventing efficient, scalable, and environmentally sound methods” for building, from scratch, molecules produced in nature. Many of these natural products have medicinal properties. Baran has already concocted a host of natural products, including those with the ability to kill bacteria or cancer cells. In addition to emphasizing the important pharmaceutical applications of his work, Baran embraces its creative aspects: “The area of organic chemistry is such a beautiful one because one can be both an artist and an explorer at the same time,” he said in the MacArthur video interview Exit icon.

Learn more:

NIGMS “Meet a Chemist” Profile of Baran
NIH Director’s Blog Post on Baran’s Recent Work