You are currently browsing the archives for the Interesting Studies category.

Archive for the ‘Interesting Studies’ Category

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.

How Statistics Can Help Minimize Scientific Retractions

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

The ability to duplicate an experiment and its results is a central tenet of the scientific method, but recent research has shown an alarming number of peer-reviewed papers are irreproducible.

A team of math and statistics professors has proposed a way to address one root of that problem by teaching reproducibility to aspiring scientists, using software that makes the concept feel logical rather than cumbersome.

Researchers from Smith College, Duke University and Amherst College looked at how introductory statistics students responded to a curriculum modified to stress reproducibility. Their work is detailed in a paper published Feb. 25 in the journal Technological Innovations in Statistics Education.

In 2013, on the heels of several retraction scandals and studies showing reproducibility rates as low as 10 percent for peer-reviewed articles, the prominent scientific journal Nature dedicated a special issue to the concerns over irreproducibility.

Nature’s editors announced measures to address the problem in its own pages, and encouraged the science community and funders to direct their attention to better training of young scientists.

“Too few biologists receive adequate training in statistics and other quantitative aspects of their subject,” the editors wrote. “Mentoring of young scientists on matters of rigour and transparency is inconsistent at best.”

The authors of the present study thus looked to their own classrooms for ways to incorporate the idea of reproducibility.

Read more…

3D Printer Used to Print Vascularized Human Tissue

 :: Posted by American Biotechnologist on 02-27-2014

The Wyss Institute at Harvard University is using engineering principles to build living things, and create biologically inspired materials and devices. In this really cool video, scientists use a custom built 3D printer to print vascularized tissue which will eventually be used as replacements for damaged human tissue.

To read more about this story see An Essential Step toward Printing Living Tissues.

A Genetic Explanation of Why You May Look More Like Your Mother

 :: Posted by American Biotechnologist on 02-24-2014

We are a product of our parents. Maybe you have your mother’s large, dark eyes, and you inherited your father’s infectious smile. Both parents contribute one copy, or allele, of each gene to their offspring, so that we have two copies of every gene for a given trait – one from mom, the other from dad. In general, both copies of a gene are switched on or off as an embryo develops into an adult. The “switching on” of a gene begins the process of gene expression that ultimately results in the production of a protein.

Occasionally, a cell will arbitrarily begin to use of one copy of a gene over the other. The activation of only one member of a gene pair is called ”monoallelic gene expression.” In work published today in Developmental Cell, a team of researchers led by Professor David Spector at Cold Spring Harbor Laboratory (CSHL) shows that this random phenomenon is far more likely to be found in mature, developed cell types than in their stem cell precursors. This, in turn, offers an unexpected glimpse of randomness and variability in gene expression.

Cells are exquisitely sensitive to protein amounts: too much or too little can give rise to diseases, including cancer. For example, certain proteins, called tumor suppressors, act as “stop” signals to restrain cell growth. A cell with only half the dosage of such a protein may become the seed of a tumor. Random monoallelic gene expression cuts the amount of a protein by half, suggesting that this type of variability may have significant implications for disease.

Spector and Mélanie Eckersley-Maslin, Ph.D., lead author on the new paper, found that monoallelic gene expression is truly a random process. “It is not deterministic in any way,” says Spector. “This significant amount of flexibility and randomness in gene expression is important for adaptation as a species evolves, but it is unclear how it functions in organisms today.”

To better understand when monoallelic gene expression is established, Spector and his team collaborated with researchers from the European Molecular Biology Laboratory. The team used advanced sequencing technology and analysis tools to globally assess allele usage in two different cell types. They compared embryonic stem cells, which can change, or “differentiate,” into nearly any type of tissue, with cells that had already differentiated into the precursors of neurons. They found a 5.6-fold increase in the number of monoallelically expressed genes in the differentiated cells. “As differentiation occurs, there is a dramatic change in gene expression as a specific program or set of genes is selected to be expressed and a massive reorganization occurs in the nucleus,” says Spector. “It is these enormous changes that lead to stochastic (i.e., variable) monoallelic expression.”

The team was surprised to find that 8% of the monoallelically expressed genes were able to boost their level of expression to compensate for what would otherwise be a shortfall. The researchers speculate that the cell may require higher amounts of protein from those genes. “This work raises many important questions,” says Spector, “such as: how does the cell know how much of each protein to produce? How much flexibility is there? What is the tipping point toward disease?” The team continues to explore these fascinating questions.

This work was supported by the National Institute of General Medical Sciences and the National Cancer Institute, a Genentech Foundation Fellowship, George A. and Marjorie H. Anderson Fellowship, Deutscher Akademischer Austauschdienst Postdoctoral Fellowship, the European Molecular Biology Laboratory, and the Wellcome Trust.

“Random Monoallelic Gene Expression Increases upon Embryonic Stem Cell Differentiation” appears online in Developmental Cell on February 24, 2014. The authors are: Mélanie A. Eckersley-Maslin, David Thybert, Jan H. Bergmann, John C. Marioni, Paul Flicek, and David L. Spector. The paper can be obtained online at: http://www.cell.com/developmental-cell/home

Thanks to Cold Spring Harbor Laboratory for contributing this story.