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Archive for the ‘Interesting Studies’ Category

Suprise! mRNA and Protein Levels Do Not Always Correspond!

 :: Posted by American Biotechnologist on 03-27-2014

The central dogma of molecular biology states that DNA codes for RNA and RNA codes for protein. It was widely understood that because protein is translated from mRNA, the amount of mRNA in a cell would somewhat correspond to the quantity of cellular protein. In a new study out of Notre Dame, scientists have shown that this theory is not always correct. While in many cases mRNA and protein levels do correspond, there are a surprisingly high number of exceptions, demonstrating that the amounts of a particular protein can be controlled by multiple mechanisms.

Bioanalytical chemist Norman Dovichi and molecular biologist Paul Huber identified and measured the levels of about 4,000 proteins, which exhibited patterns of expression that reflect key events during early Xenopus development resulting in the largest data set on developmental proteomics for any organism.

The study was conducted in Xenopus laevis embryos, which is a favored model for this type of research. In Xenopus, development takes place in well-defined stages outside the mother, thereby allowing embryogenesis to be monitored in real time. Additionally, embryos develop rapidly, achieving a nearly fully developed nervous system within four days.

Their results are available open access in Scientific Reports.

Dissecting a Two-Faced Calf

 :: Posted by American Biotechnologist on 03-25-2014

What’s the strangest thing you have ever dissected?

Powerful New Tool for Studying DNA Elements that Regulate Genes

 :: Posted by American Biotechnologist on 03-24-2014

An international team led by researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) has developed a new technique for identifying gene enhancers – sequences of DNA that act to amplify the expression of a specific gene – in the genomes of humans and other mammals. Called SIF-seq, for site-specific integration fluorescence-activated cell sorting followed by sequencing, this new technique complements existing genomic tools, such as ChIP-seq (chromatin immunoprecipitation followed by sequencing), and offers some additional benefits.

“While ChIP-seq is very powerful in that it can query an entire genome for characteristics associated with enhancer activity in a single experiment, it can fail to identify some enhancers and identify some sites as being enhancers when they really aren’t,” says Diane Dickel, a geneticist with Berkeley Lab’s Genomics Division and member of the SIF-seq development team. “SIF-seq is currently capable of testing only hundreds to a few thousand sites for enhancer activity in a single experiment, but can determine enhancer activity more accurately than ChIP-seq and is therefore a very good validation assay for assessing ChIP-seq results.”

Dickel is the lead author of a paper in Nature Methods describing this new technique. The paper is titled “Function-based identification of mammalian enhancers using site-specific integration.”

Read more…

Going Beyond the Central Dogma of Molecular Biology

 :: Posted by American Biotechnologist on 03-18-2014

Our genome, we are taught, operates by sending instructions for the manufacture of proteins from DNA in the nucleus of the cell to the protein-synthesizing machinery in the cytoplasm. These instructions are conveyed by a type of molecule called messenger RNA (mRNA).

Francis Crick , co-discoverer of the structure of the DNA molecule, called the one-way flow of information from DNA to mRNA to protein the “central dogma of molecular biology.”

Yehuda Ben-Shahar and his team at Washington University in St. Louis have discovered that some mRNAs have a side job unrelated to making the protein they encode. They act as regulatory molecules as well, preventing other genes from making protein by marking their mRNA molecules for destruction.

“Our findings show that mRNAS, which are typically thought to act solely as the template for protein translation, can also serve as regulatory RNAs, independent of their protein-coding capacity,” Ben-Shahar said. “They’re not just messengers but also actors in their own right.” The finding was published in the March 18 issue of the new open-access journal eLife.

Although Ben-Shahar’s team, which included neuroscience graduate student Xingguo Zheng and collaborators Aaron DiAntonio and his graduate student Vera Valakh, was studying heat stress in fruit flies when they made this discovery, he suspects this regulatory mechanism is more general than that.

Many other mRNAs, including ones important to human health, will be found to be regulating the levels of proteins other than the ones they encode. Understanding mRNA regulation may provide new purchase on health problems that haven’t yielded to approaches based on Crick’s central dogma.

Read the full story A novel mechanism for fast regulation of gene expression.

Computational Tool Offers New Insight Into Key Biological Processes

 :: Posted by American Biotechnologist on 03-06-2014

Researchers from North Carolina State University have developed a computational tool designed to guide future research on biochemical pathways by identifying which components in a biological system are related to specific biochemical processes, including those processes responsible for gene expression, cell signaling, stress response, and metabolism.

“Our goal was to identify modules, or functional units, which are critical to the performance of the biochemical pathways that govern a host of biological processes,” says Dr. Cranos Williams, an assistant professor of electrical and computer engineering at NC State and senior author of a paper describing the work.

“For example, a car has lots of modules – the parts that make it go, the parts that make it stop, the parts that let you steer, etc. If you understand those modules, you understand how the car works. But if you just have a list of parts, that’s not very helpful.

“And what we have right now for many biochemical pathways is essentially just a list of parts – metabolites, biochemical reactions and enzymes that facilitate those reactions – and, in some cases, how those parts change over time. What we need is a clear understanding of which parts work together. That’s where our new algorithm comes in.”

The researchers developed an algorithm that allows them to identify which parts – the metabolites, reactions and enzymes – are related to each other and can be grouped into functional modules. The algorithm also identifies whether an individual component plays a role in multiple modules. For example, an enzyme may play a primary role in critical stress response pathways and a secondary role in processes associated with programmed cell maintenance or death.

The algorithm also characterizes how the relationships between different modules and individual components may change over time and under different internal and external conditions.

The input for the algorithm comes from using well-established dynamic models to observe changes in concentrations of metabolites, reactions and enzymes under various conditions. The algorithm then processes that data to establish primary and secondary relationships between all of the constituent parts.

“When modifying biological processes, there are thousands of possible combinations of metabolites, reactions and enzymes for any given biochemical pathway,” Williams says. “Our work should help life scientists narrow down the list of key players in order to target their research efforts on functional groups that are most likely to improve our ability to understand and control important biological processes. This has applications in everything from biomedical research to agriculture to biofuels.”

The paper, “Hierarchical Modularization Of Biochemical Pathways Using Fuzzy-C Means Clustering,” is forthcoming from IEEE Transactions on Cybernetics. Lead author of the paper is Dr. Maria de Luis Balaguer, a former Ph.D. student at NC State.

Thanks to North Carolina State University for contributing this story.