Category: Genes

Posted on

One Mutation Leads to Another—At Least in Yeast

by
0 comments
DNA mutation. Credit: Stock image.
Newly discovered genetic effect in yeast could shed light on carcinogenesis. Credit: Stock image.

Cancer cells typically include many gene mutations, extra or missing genes, or even the wrong number of chromosomes. Scientists know that certain genetic changes lead to ones elsewhere. But they’ve had a chicken-and-egg problem trying to figure out which changes trigger which others—or whether mutations accumulate randomly in tumors.

New research led by J. Marie Hardwick Exit icon of Johns Hopkins University sheds light on the issue. She found that incapacitating a single gene in yeast cells—regardless of which gene it was—spurred mutations in one or two other genes. The process was anything but random: If, say, gene X was knocked out, yeast cells almost always developed a secondary mutation in gene Y. It’s as if knocking out one gene disrupts the genomic balance enough that the cell must alter a different gene to compensate.

Significantly, the secondary mutations—but not the original ones—caused altered yeast cell characteristics, including traits linked to cancer. Also, many of the secondary mutations occurred in genes associated with cancer in humans, further suggesting that these secondary changes might play a role in carcinogenesis.

This new information will help researchers better understand the chain of genetic events that lead to cancer. It might also prompt scientists to reevaluate years of research that attributed changes in cell behavior or appearance to a given gene knockout.

This work also was funded by NIH’s National Institute of Neurological Disorders and Stroke.

Learn more:
Johns Hopkins University News Release Exit icon

Posted on

Abnormal Mitochondria Might Cause Resistance to Radiation Therapy

by
2 comments
Mitochondria. Credit: Judith Stoffer.
Bean-shaped mitochondria are cells’ power plants. The highly folded inner membranes are the site of energy generation. Credit: Judith Stoffer. View larger image

Why some cancers are resistant to radiation therapy has baffled scientists, but research on abnormalities in mitochondria, often described as cells’ power plants, could offer new details. A research team led by Maxim Frolov Exit icon of the University of Illinois at Chicago learned that the E2F gene, which plays a role in the natural process of cell death, contributes to the function of mitochondria. Fruit flies with a mutant version of the E2F gene had misshapen mitochondria that produced less energy than normal ones. Flies with severely damaged mitochondria were more resistant to radiation-induced cell death. Studies using human cells revealed similar effects. The work could help explain why people with cancer respond differently to radiation therapy and might aid the development of drugs that enhance mitochondrial function, thereby improving the effectiveness of radiation therapy.

This work also was funded by NIH’s National Cancer Institute.

Learn more:
University of Illinois at Chicago News Release Exit icon

Posted on

Stop the (Biological) Clock

by
0 comments
Molecular structure of the three proteins in blue-green algae’s circadian clock. Credit: Johnson Lab, Vanderbilt University.
Molecular structure of the three proteins in blue-green algae’s circadian clock. Credit: Johnson Lab, Vanderbilt University.

Many microorganisms can sense whether it’s day or night and adjust their activity accordingly. In tiny blue-green algae, the “quartz-crystal” of the time-keeping circadian clock consists of only three proteins, making it the simplest clock found in nature. Researchers led by Carl Johnson of Vanderbilt University recently found that, by manipulating these clock proteins, they could lock the algae into continuously expressing its daytime genes, even during the nighttime.

Why would one want algae to act like it’s always daytime? The kind used in Johnson’s study is widely harnessed to produce commercial products, from drugs to biofuels. But even when grown in constant light, algae with a normal circadian clock typically decrease production of biomolecules when nighttime genes are expressed. When the researchers grew the algae with the daytime genes locked “on” in constant light, the microorganism’s output increased by as much as 700 percent. This proof of concept experiment may be applicable to improving the commercial production of compounds such as insulin and some anti-cancer drugs.

Learn more:

Vanderbilt University Press Release Exit icon
Johnson Laboratory Exit icon
Circadian Rhythms Fact Sheet

Posted on

Genetic Discovery Could Enable More Precise Prescriptions

by
0 comments
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)

Posted on

NIH Director Blogs About Value of Model Organisms in Drug Discovery Research

by
0 comments
(Left) Untreated yeast cells, (Right) Treated yeast cells. Credit: Daniel Tardiff, Whitehead Institute.
Treating yeast cells with the NAB compound reverses the toxic effects of elevated levels of alpha synuclein protein. Credit: Daniel Tardiff, Whitehead Institute. View larger image

These eye-catching images and the NIGMS-funded research that yielded them were recently featured by NIH Director Francis Collins on his blog. Scientists led by a team at the Whitehead Institute for Biomedical Research engineered yeast to produce too much of a protein, alpha synuclein. In Parkinson’s disease, elevated levels or mutated forms of this protein wreak havoc on the cell. Using the model system, the researchers tested tens of thousands of compounds to identify any that reversed the toxic effects. One did. The compound, abbreviated NAB, worked similarly in an animal model and in rat neurons grown in a lab dish. Collins described the approach as “an innovative strategy for drug hunting that will likely be extended to other conditions.”

Posted on

Healing Wounds, Growing Hair

by
1 comment
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

Posted on

Flu Finds a Way In

by
0 comments
Influenza virus proteins in the act of self-replication. Credit: Wilson, Carragher and Potter labs, Scripps Research Institute.
Influenza virus proteins in the act of self-replication. Credit: Wilson, Carragher and Potter labs, Scripps Research Institute.

Flu viruses evolve rapidly, often staying one step ahead of efforts to vaccinate against infections or treat them with antiviral drugs. Work led by Jesse Bloom of the Fred Hutchinson Cancer Research Center has uncovered a surprising new flu mutation that allows influenza to infect cells in a novel way. Normally, a protein called hemagglutinin lets flu viruses attach to cells, and a protein called neuraminidase lets newly formed viruses escape from infected cells. Bloom’s lab has characterized a mutant flu virus where neuraminidase can enable the virus to attach to host cells even when hemagglutinin’s binding is blocked. Although the researchers generated the neuraminidase mutant studied in these experiments in their lab, the same mutation occurs naturally in strains from several recent flu outbreaks. There’s a possibility that flu viruses with such mutations may be able to escape antibodies that block the binding of hemagglutinin.

This work also was funded by NIH’s National Institute of Allergy and Infectious Diseases.

Learn more:

Bloom Lab Exit icon

Posted on

New Approach Subtypes Cancers by Shared Genetic Effects

by
0 comments
Cancer

Cancer tumors are like snowflakes—no two ever share the same genetic mutations. Their unique characteristics make them difficult to categorize and treat. A new approach proposed by Trey Ideker and his team at the University of California, San Diego, might offer a solution. Their approach, called network-based stratification (NBS), identifies cancer subtypes by how different mutations in different cancer patients affect the same biological networks, such as genetic pathways. As proof of principle, they applied the method to ovarian, uterine and lung cancer data to obtain biological and clinical information about mutation profiles. Such cancer subtyping shows promise in helping to develop more effective, personalized treatments.

Learn more:

University of California, San Diego News Release
Ideker Lab

Posted on

How Some Bacteria Colonize the Gut

by
1 comment
A section of mouse colon with gut bacteria (center, in green). Credit: S. Melanie Lee, Caltech; Zbigniew Mikulski and Klaus Ley, La Jolla Institute for Allergy and Immunology.
A section of mouse colon with gut bacteria (center, in green) residing within a protective pocket. Credit: S. Melanie Lee, Caltech; Zbigniew Mikulski and Klaus Ley, La Jolla Institute for Allergy and Immunology.

Have you ever felt that your gut was trying to tell you something? The guts of germ-free mice have told scientists a few new things about our resident microorganisms. By studying a genus of bacteria called Bacteriodes that live in the gastrointestinal tract, Sarkis Mazmanian of the California Institute of Technology discovered how Bacteriodes species stake their claim in a mouse’s gut. Mazmanian and his colleagues introduced different species of Bacteriodes into germ-free mice to learn how the microbes competed and found that most of them peacefully co-existed. However, when microbes of a species that was already present were introduced, they couldn’t take up residence. Further investigation revealed that Bacteriodes species, due to a set of specific genes, can live in tiny pockets or “crypts” of the colon, where they are sheltered from antibiotics and infectious microbes passing through. Understanding how these microorganisms colonize could help devise ways to correct for abnormal changes in bacterial communities that are associated with disorders like inflammatory bowel disease.

This work also was funded by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases.

Learn more:

California Institute of Technology News Release
Mazmanian Lab
Mazmanian Video Interview Exit icon

Posted on

Making Strides in Genomic Engineering of Human Stem Cells

by
1 comment
Genetically engineered human stem cells. Credit: Jeff Miller, University of Wisconsin-Madison.
Genetically engineered human stem cells hold promise for basic biomedical research as well as for regenerative medicine. Credit: Jeff Miller, University of Wisconsin-Madison.

Human pluripotent stem cells (hPSCs) can multiply indefinitely and give rise to virtually all human cell types. Manipulating the genomes of these cells in order to remove, replace or correct specific genes holds promise for basic biomedical research as well as medical applications. But precisely engineering the genomes of hPSCs is a challenge. A research team led by Erik Sontheimer of Northwestern University and James Thomson of the Morgridge Institute for Research at the University of Wisconsin-Madison developed a technique that could be a great improvement over existing, labor-intensive methods. Their approach uses an RNA-guided enzyme from Neisseria meningitidis bacteria—part of a recently discovered bacterial immune system—to efficiently target and modify specific DNA sequences in the genome of hPSCs. The technique could eventually enable the repair or replacement of diseased or injured cells in people with some types of cancer, Parkinson’s disease and other illnesses.

This work also was funded by NIH’s National Center for Advancing Translational Sciences.

Learn more:

Thomson Bio Exit icon