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Integrated Stress Response

The integrated stress response (ISR) is an evolutionarily conserved intracellular signaling network that helps the cell properly respond to stressors such as viral infection, toxic compounds, nutrient deprivation, and more. A longstanding problem in understanding how cells communicate stress signals has been the lack of a method to control and precisely activate the stress response of a single cell without affecting its neighbors. Our lab recently overcame this hurdle through the development of an optogenetic tool that allows us to virtually activate the stress response with light. Thus, we are able to induce the stress response in single cells to uncover the underlying mechanisms of the ISR. We are investigating how this pathway functions to make decisions that cells use to respond to stress. Is this stress communicated to its neighbors? What effects does the ISR have on the extracellular matrix, and how does this affect diseases such as cystic fibrosis?

 

Highlighted Publications

Optogenetic control of the integrated stress response reveals proportional encoding and the stress memory landscape. Taivan Batjargal, Francesca Zappa, Ryan J. Grant, Robert A. Piscopio, Alex, Chialastri, Siddharth S. Dey, Diego Acosta-Alvear, and Maxwell Z. Wilson. Cell Systems. (Download PDF)

Triggered Functional Dynamics of AsLOV2 by Time-Resolved Electron Paramagnetic Resonance at High Magnetic Fields. Shiny Maity, Brad D. Price, Blake C. Wilson, Arnab Mukherjee, Matthieu Starck, David Parker, Maxwell Z. Wilson, Janet E. Lovett, Songi Han, and Mark S. Sherwin. Angewandte Chemie. (Download PDF)

Optogenetic control of the integrated stress response reveals proportional encoding and the stress memory landscape. Taivan Batjargal, Francesca Zappa, Ryan J Grant, Robert A Piscopio, Alex Chialastri, Siddharth S Dey, Diego Acosta-Alvear, Maxwell Z Wilson. Preprint in bioRxiv. (Download PDF)

Signaling by the integrated stress response kinase PKR is fine-tuned by dynamic clustering. Francesca Zappa, Nerea L. Muniozguren, Maxwell Z. Wilson, Michael S. Costello, Jose Carlos Ponce-Rojas, Diego Acosta-Alvear. Journal of Cell Biology.(Download PDF) 

 

Affiliated Researchers

Max Wilson

Associate Professor
Combines tools from Biology, Engineering, and Physics to understand the cell’s perceptual field.

Taivan Batjargal

Graduate Student
Taivan is interested in the underlying mechanisms of the integrated stress response (ISR). He is developing a novel optogenetic protein kinase receptor driven ISR circuit to acutely tune the levels of stress response that a cell experiences. Leveraging this tool, he studies how stress dynamics affect the cell's response to stress, and the phenotypes that result from it, be it death or adaptation. Additionally, spatiotemporal precision of the tool is utilized to observe cell to cell communication of stress events, and effects of ISR on the ECM.

Roberto Rodrigues Reyes

Graduate Student
Roberto's research involves understanding the mechanisms of the integrated stress response (ISR) by using optogenetics. By using a light to induce the ISR, we can study the ISR pathway with precision and control that was unattainable previously. Specifically, Roberto is interested in learning if ISR-activated cells will secrete 'stress' molecules that would signal neighboring cells of incoming 'stress'. 

Ethan Dickson

Graduate Student
Ethan is utilizing optogenetics to investigate the Integrates Stress Response (ISR) within the NCI-60 suite of cancer cell lines. Through this optogenetic method in combination with fluorescent reporters of signals downstream of integrated stress response activation, Ethan is hoping to illuminate the effect specific activation of the ISR has on differing cancers and mortal cells with a focus on understanding its effect on age related characteristics.