Three students participated with Dr. R. Wesley Rose, Assistant Professor of Biology, at the American Society for Cell Biology meeting at the Pennsylvania Convention Center in December. Michael Podolsky ’11, Selina Eckert ’11, and Andreas Solomos ’11 are Biology majors who work in Rose’s research lab.

Podolsky and Solomos presented a poster on “Extended JAK Activation and Delayed STAT1 Dephosphorylation Contribute to the Altered Signal Transduction Kinetics in CNS Neurons Exposed to IFN gamma,” which is the project that they’ve been working on in the lab for their senior Capstone project. The paper also is coauthored by Glenn F. Rall of Immune Cell Development and Host Defense at the Fox Chase Cancer Center in Philadelphia.

Read the abstract: “The immune cytokine interferon gamma (IFNg) plays a crucial role in many immune processes of the CNS, especially those involved in the elimination of viral infections of neurons. However, the response to IFNg has not been extensively characterized in CNS neurons.

It is therefore a long-term goal of our lab to characterize the responses of CNS neurons to IFNg that result in the noncytolytic clearance of viral infections. As the next step toward this goal, it was the overall objective of this study to define the kinetics of the neuronal IFNg signal transduction pathway that govern the transcriptional responses of the neurons. Specifically, the nature of the mechanisms that control the IFNg responsiveness of CNS neurons were examined. We previously demonstrated that the IFNg response at both the signaling and transcription levels is markedly extended in primary CNS neurons, as compared to primary mouse embryo fibroblasts (MEF). We therefore hypothesized that the kinetics of the negative feedback mechanisms that control the neuronal IFNg response are delayed as compared to those observed in non-neuronal cells. In the present study, we provide evidence that in response to IFNg, the neuronal IFNg receptor (IFNgR) complex remains active for an extended period of time as compared to MEF. In addition, we show that artificial inactivation of the IFNgR complex after IFNg treatment does not eliminate extended STAT1 phosphorylation as it does in MEF. These results indicate that the extended kinetics of neuronal IFNg signaling are a product of altered negative feedback mechanisms at both the levels of the receptor and STAT1 inactivation. Such responses may afford a survival advantage to neurons, perhaps through induction of pro-survival genes, and/or by minimizing neuronal loss. Gaining a better understanding of the way by which CNS neurons respond to IFNg will ultimately aid in the long-term goal of characterizing the immune mechanisms that operate in the CNS under pathogenic conditions. “