RNA

Sharing MCB Science: The Dynamic Transcriptional Response to Oxidative Stress

A common source of molecular damage in organisms is through oxidation, which can occur through natural processes, such as aerobic respiration, and from exposure to toxins such as ultraviolet radiation or pollution. Molecules that cause oxidation, known as reactive oxygen species (ROS), cause damage to proteins and DNA in cells and create a cell state of oxidative stress. In a recent study published in PLOS Genetics, MCB-funded investigator Dr. Amy Schmid and her team of researchers at Duke University describe the hierarchical dynamic response to oxidative stress in archaea, a single-cell model organism which has a gene regulation system similar to bacteria and eukaryotic cells.

This dynamic response controls the expression of over 100 genes whose RNA and protein products work to repair cellular damage caused by exposure to ROS. A key characteristic of this response is the presence of regulatory proteins which facilitate a sequential process to control damage repair. First, the proteins target genes to address cellular damage, then target genes to restore normal cellular function. Because the regulatory proteins involved in the response to stress are of a hybrid ancestry, these findings suggest that the evolution of gene networks may have been influenced by environmental forces, such as oxidative stress. When asked about the broader implications of her work, Dr. Schmid responded, “The results demonstrate that regulatory proteins of ancient evolutionary ancestry in archaea provide mechanistic links between various stress responses as well as between the regulatory network and its effects on cell physiology (e.g. transcriptional regulation, metabolic activity, growth rate, and cell morphology). These results have made significant progress in understanding gene network function, how it may be integrated with cell physiology, and how the network may evolve in response to stress throughout the tree of life”

The reported research was conducted by a team of varied experience and comprised graduate student Peter Tonner, research associates Adrianne Pittman and Kriti Sharma, and undergraduate researcher Jordan Gulli. As a result, trainees were integrated into research that addressed open questions in the fields of microbiology and mathematical modeling. In addition, the Schmid group hosts undergraduate students from Historically Black Colleges and Universities for summer research experiences and teaches a weeklong immersion course for high school students in collaboration with K-12 teachers. In this course, an interdisciplinary team of computational and experimental graduate students teaches high school students about mathematical modeling of microbial growth and response to oxidative stress.

Sharing MCB Science: Watching the STARs (Small Transcription Activating RNAs)

The editors are excited about the first of what we hope to be many blog posts featuring the science of MCB-funded investigators. We plan to share a broad sampling of this research and its outcomes on our blog. If you are a) an MCB-funded researcher and b) have recently published research that you would like to share, please fill out this form to be considered for a featured post.

RNA is an important molecule found in all living organisms. To use a computer analogy, RNA acts like a circuit board, controlling DNA, nature’s hard drive. RNA helps to read genetic information and enact the programs of life, through proteins and other important biologic materials. Dr. Julius Lucks, along with post-doctoral associate James Chappell and graduate student Melissa Takahashi, has capitalized on the ability of RNA to form different folded structures via complementary base pairing to create Small Transcription Activating RNAs or STARs. STARs are a molecular “on-switch”, whose shape controls the state (off or on) of the switch. In their recent paper in Nature Chemical Biology, the Lucks Lab researchers describe using STARs to activate the first steps in gene expression (the “printing out” of proteins) in bacteria. The researchers also provide data to support the idea of snapping STARs together to create advanced genetic programs within bacteria.  These examples demonstrate the potential application of STARS to allow bioengineers or synthetic biologists to write new genetic programs, which could engineer cells to address health and environmental challenges. Ongoing research in the lab is focused on using STARs for molecular diagnostics.

The research group is committed to broader impacts and they have recently created a summer course at Cold Spring Harbor Laboratories in Synthetic Biology, where they collaborate with other synthetic biology researchers to develop an ideal training ground for students interested in learning more about the field. Students range from first-year graduate students, to industry professionals, to senior Professors. The course, which has been held for the past 3 summers, is interactive, incorporating research, top-notch guest speakers, and hands-on activities.

To engage the broader community in synthetic biology, the Lucks Lab is closely collaborating with the Sciencenter in Ithaca, NY,as part of the NSF-funded “Multi-Site Public Engagement with Science – Synthetic Biology” project. The goal of the project is to create hands-on activities for children and their families. For example, the group is working on developing a card game that can teach adults and children about the basics of synthetic biology. The cards feature images and facts about engineered microbes, such as, how microbes help humans create important medicines.

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