December 28 Research Roundup: Super Leukemia Drug, Synthetic Antibiotics, How Marijuana Changes the Genetics of Sperm, and More
There are plenty of great scientific research stories out this week. Here’s a look at just a few of them.
Super Drug for Pediatric Leukemia
Researchers at Northwestern University have found two drugs that slowed the progress of pediatric leukemia in mice. They have published three studies over the last two years, with the final paper published recently in Genes & Development.
The most recent study found that when a key protein is stabilized, leukemia progression slows. In children diagnosed with MLL-translocation leukemia, the survival rate is only 30 percent. The two most common types of pediatric leukemias are acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL).
“These white blood cells infiltrate many of the tissues and organs of the affected individuals and is a major cause of death in leukemia patients,” stated Ali Shilatifard, senior author and the Robert Francis Furchgott Professor of Biochemistry and Molecular Genetics and Pediatrics. “This is a monster cancer that we’ve been dealing with for many years in children.”
Possible New Approach to Synthesizing Antibiotics
University of Colorado Boulder chemists developed a new way to synthesize and optimize a naturally-occurring compound that has potential to treat drug-resistant infections. The work is built on the concept of thiopeptides, which are naturally-occurring antibiotic compounds, and have shown some effectiveness against methicillin-resistant Staphylococcus aureus (MRSA) and other species of bacteria. But thiopeptides are difficult to synthesize.
“We re-evaluated the structural commonalities of these thiopeptides in light of current superbugs, because no one had looked at them and analyzed them in modern context,” stated Maciej Walczak, lead author of the research and an assistant professor in CU Boulder’s Department of Chemistry.
They developed a new catalyst that drives reactions that help the synthesis of the thiopeptides. Their work, published in the journal Chemical Science, describes two new broadly representative antibiotics, micrococcin P1 and thiocillin I.
Genes Linked to Eye Disease, at Least in Mice
Researchers at the University of California, Davis, part of the International Mouse Phenotyping Consortium, identified hundreds of new genes in mice linked to blindness and other vision disorders. The research was published in Nature Communications Biology.
“This is extremely valuable for people with hereditary eye disease,” stated Ala Moshiri, associate professor of ophthalmology and vision science at the UC-Davis’ School of Medicine and Eye Center. “The whole ophthalmic community is going to start using these data.”
The consortium has generated more than 7,000 strains of gene-knockout mice, and 4,364 have been characterized across 11 organ systems. Previous gene sets were associated to deafness, genes essential to life, and even some linked to hereditary bad breath. This group identified 347 genes, 86 which were either already linked to eye disease or associated with vision, while 261 genes were not previously linked to cause eye disease in mice.
New and Improved Single-Cell RNA Sequencing
Single-cell RNA sequencing is a low-cost, high-throughput technique for single-cell genomics. But it doesn’t always capture complete RNA transcription data. Now, researchers at Cornell University have developed a technique that improves upon it. Their research was published in the journal Nature Methods.
The technique is called DART-seq (droplet-assisted RNA targeting by single-cell sequencing). In it, individual cells are encapsulated with labeled microparticles that launch reverse transcription of cellular mRNA. The researchers created an effective method to enzymatically customize the beads before performing conventional Drop-seq analysis. This allows for recovery and subsequent analysis of more molecules than was available through Drop-seq sequencing.
Marijuana Exposure Affects the Genetic Profile of Sperm
Researchers at Duke University Medical Center investigated the effect of THC exposure, the psychoactive ingredient in cannabis, on the epigenetics of sperm. They published their research in the journal Epigenetics. The results were similar those found in exposure to tobacco smoke, pesticides, flame retardants and even obesity—largely negative.
Exposure to THC triggers structural and regulatory changes in the DNA of sperm in marijuana users. The team conducted research on both rats and 24 men. THC appears to affect genes in two major cellular pathways and alters DNA methylation, which affects how genes are turned on and off. It’s not yet known if the changes to the sperm are passed along to any children or what the effects might be.
“We know that there are effects of cannabis use on the regulatory mechanisms in sperm DNA, but we don’t know whether they can be transmitted to the next generation,” stated lead author Susan K. Murphy, associate professor and chief of the Division of Reproductive Sciences in obstetrics and gynecology at Duke. “In the absence of a larger, definitive study, the best advice would be to assume these charges are going to be there. We don’t know whether they are permanent. I would say, as a precaution, stop using cannabis for at least six months before trying to conceive.”
How Skin Ages
Dermal fibroblasts are specialized skin cells. They create the connective tissue for skin and assist in recovering from injury. Some fibroblasts can change into fat cells that live just under the dermis, which gives the skin a young look. It also creates a chemical that plays a pivotal role in fighting infections. Researchers with the University of California, San Diego (UCSD) School of Medicine published research in the journal Immunity that described how fibroblasts change into fat cells and identified the pathway that stops functioning as people age.
Much of it is related to a protein called transforming growth factor beta (TGF-b). This protein stops dermal fibroblasts from converting into fat cells. It also prevents cells from creating the antimicrobial peptide cathelicidin.
“Babies have a lot of this type of fat under the skin, making their skin inherently good at fighting some types of infections,” stated Richard Gallo, senior author of the study and Distinguished Professor and chair of the Department of Dermatology at UC San Diego School of Medicine. “Aged dermal fibroblasts lose this ability and the capacity to form fat under the skin. Skin with a layer of fat under it looks more youthful. When we age, the appearance of the skin has a lot to do with the loss of fat.”