This month, Insights & Outcomes kicks off the new semester with a dash of quantum chemistry, a smidgen of beta cells and choosy enzymes, and a bunch of spud-spoiling bacteria.
Spoiling spuds with a pathogen trick
To the bane of potato farmers, bacteria that invade plants have developed a neat trick — they can essentially alter their own genetic code. Yale researchers have discovered that bacteria from the genus Streptomyces can deliberately mistranslate their own genetic instructions.
While Streptomyces is best known for being a rich source of antibiotics and other bioactive molecules, a small group of Streptomyces species are pathogenic and wreak havoc on annual potato crops. Yale’s Oscar Vargas-Rodriguez and Sergey Melnikov, both from the lab of Dieter Söll, the Sterling Professor of Molecular Biophysics and Biochemistry, discovered how these bacteria manage this feat.
According to the rules of the genetic code, proteins that carry out cellular functions are created from combinations of 20 different amino acids. The specific combination of amino acids within a protein is based on information stored in the DNA and translated by the ribosome, the cell’s protein-making machinery. Key components in this process are aminoacyl-tRNA synthetase enzymes and transfer RNAs (tRNAs).
The Yale team found that some Streptomyces have evolved a new pair of aminoacyl-tRNA synthetase and tRNA molecules that allow the bacteria to change the genetic instructions contained in DNA and insert the amino acid proline at positions that should contain alanine. Essentially, the process allows the bacteria to mistranslate instructions from its own DNA, thereby altering the biochemical architecture of its proteins. Söll and Vargas-Rodriguez speculate that, for the bacteria, having the ability to quickly diversify their protein pool may be a key survival tool in times of stress, and possibly serves as a mechanism to avoid a plant’s immune defenses or increase pathogenicity during infection.
Their study appears in the journal Proceedings of the National Academy of Sciences.
Yale to launch and lead a quantum computing chemistry center
Yale will lead a new project to simulate the dynamics of complex chemical reactions using quantum computing technology.
The new Center for Quantum Dynamics on Modular Quantum Devices, led by Victor Batista, the John Randolph Huffman Professor of Chemistry, is Yale’s first project for quantum computing in chemistry. The National Science Foundation Centers for Chemical Innovation awarded a $1.8 million grant for the center, which aims to bridge the gap between today’s quantum computing tech and the problems for which a quantum computer could be useful in chemistry research.
For example, quantum computing could be used to study chemical reaction dynamics, such as the reactions that initiate the process of vision in the human retina. Yale will contribute to the project by developing a new generation of quantum processors and algorithms.
Batista is a member of the Yale Quantum Institute and the Energy Sciences Institute at West Campus. Collaborators in the new center are Michel Devoret, the F.W. Beinecke Professor of Applied Physics and Physics at Yale, Kais Saber at Purdue University, Lea Ferreira Dos Santos of Yeshiva University, and Eitan Geva of the University of Michigan.
Building a better beta cell
In Type 1 diabetes, immune system cells attack insulin-producing beta cells in the pancreas, leaving patients dependent upon a life-long course of insulin injections for survival. In a novel twist to the story, a Yale research team has discovered that beta cells may harbor the seeds of their own destruction.
In a new study, a team led by Yale immunologist Kevan Herold, the C.N.H. Long Professor of Immunobiology and of Medicine, found that the expression of a protein, TET2, within beta cells aids in the activation of the self-destructive T lymphocytes that attack beta cells. In mouse models in which the animals have Type 1 diabetes but lack TET2, pathologic T cells were not activated and did not kill beta cells.
Herold’s lab is investigating ways to eliminate TET2 in diabetic patients in an attempt to restore beta cells even in those in whom the proteins have been destroyed during the development of Type 1 diabetes. The study was published in the journal Nature Communications.
The e-cigarette knowledge gap
The health impacts of e-cigarettes have long been debated because of the products’ appeal among youth and the question of whether encouraging the use of e-cigarettes might help adults transition away from traditional cigarettes.
“There is emerging evidence that e-cigarettes help some adults quit smoking, but there are gaps in our knowledge,” said Krysten Bold, assistant professor of psychiatry and co-author of a literature review on the question. “Right now, we don’t know what to recommend. What devices should people use? For how long? We just don’t know.”
Will new and ongoing studies examining the role of e-cigarettes for smoking cessation fill the gaps? To answer that question, Yale researchers combed through dozens of completed and ongoing studies registered in the World Health Organization’s international clinical trial registries to examine whether ongoing studies will help provide new information to answer critical questions.
The review of 66 studies showed that many of them suffer from similar flaws — most had small sample sizes, lacked behavioral support for smoking cessation, did not include long-term follow-up with subjects or consider the use of newer e-cigarette devices designed to deliver nicotine more like cigarettes, the authors found.
“Our findings suggest that ongoing trials are unlikely to help answer these questions, and this is an important area for future work,” Bold said.
Yale’s Felicia Hung, Joshua Wallach (assistant professor in the Department of Environmental Health Sciences, Yale School of Public Health) and Stephanie O’Malley (the Elizabeth Mears and House Jameson Professor of Psychiatry) are co-authors of the study, which was published in the journal JAMA Psychiatry.
‘Choosy’ enzymes hit pause to find genes that fit
Researchers at Yale’s Institute of Biomolecular Design and Discovery have devised a new way to measure one of the early “pause points” in the gene expression process, when enzymes “choose” which genes are turned on and off. The study appears in the journal Molecular Cell.
To express a gene, an enzyme called RNA polymerase copies DNA into RNA, which transmits genetic code for protein creation. Though this can happen quickly, cells sometimes control whether or not the polymerase gets out of the starting gate in a process called “promoter-proximal pausing.”
“There’s a lot we don’t know about how our genes are read as part of the gene expression process, but we found that these enzymes often halt in their tracks for minutes at a time before deciding to either select or reject the gene to express,” said first author Josh room, a graduate student in the lab of Matthew Simon, associate professor in the Department of Molecular Biophysics & Biochemistry.
The team developed a method to measure the polymerase pause at the beginning of gene expression. And they combined their method with hormone treatments to show how the pause point is critical for gene expression. The findings revealed pause-release rates to be highly variable but with a surprisingly “choosy” 80% of RNA polymerase molecules prematurely terminating at this point.
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