Postdoctoral researcher Laura Strube has been an awarded an Intersect Fellowship through the American Association of Immunologists (AAI).
The AAI Intersect Fellowship for Computational Scientists and Immunologists provides salary support for postdoctoral fellows to undertake one year of training in computational science or immunology. This fellowship is designed to strengthen communication between the disciplines.
Strube is a joint postdoctoral fellow in the Department of Computational and Systems Biology and the Department of Immunology. She will use this award to enhance her knowledge of immunology, JAK-STAT signaling pathways, and computational methods for the study of biological systems.
Strube, who earned a PhD in mathematics from the University of Utah as part of the mathematical biology research group, leverages her background in mathematics to address molecular biology topics.
“My research focuses on biological paradoxes that require a systems-level perspective,” Strube said. “For example, I have used mathematical models to understand scenarios in which infection causes a population to grow. This is a paradox.”
Strube was drawn to immunology because of its abundance of such paradoxes. The Intersect Fellowship will help her transition from broad training in mathematical biology toward specialization in immunology and molecular signaling pathways.
“This is an exciting opportunity. Anytime you make a pivot in your training, whether that’s to a new biological system or to a new tool, it takes time to learn these new areas,” she said. “The award is valuable because it provides that time for individuals who want to cross train in a new discipline.”
Strube moved to Pittsburgh to work with Rachel Gottschalk and Jim Faeder on projects at the intersection of immunology and computational biology. Gottschalk is an assistant professor in the Department of Immunology and Faeder is an associate professor in the Department of Computational and Systems Biology. They will serve as principal investigator and co-principal investigator on Strube’s research project for AAI.
The title of Strube’s project is “Modeling JAK-STAT network asymmetries and context-specific signaling.” She has created an analogy to explain the concept of JAK-STAT signaling.
“Suppose something in a cell’s environment creates a signal which binds to the cell’s surface,” Strube said. “This initiates a series of internal molecular reactions that is analogous to a Rube Goldberg machine. The result is a shift in gene expression that allows the cell to appropriately respond to its environment.”
She will be studying the IL6/IL10 JAK-STAT pathway in immune cells. In this system, IL6 and IL10 are the external signals that direct the cell toward either a pro- or anti-inflammatory immune response by using JAK proteins to activate STAT proteins. This system is interesting because both signals use the same signaling network but produce distinct gene expression profiles and cellular behaviors.
Strube will use mathematical and computational tools to study how these distinct outcomes are possible within one network.
“The IL6/IL10 JAK-STAT pathway is more complex than a simple Rube Goldberg machine as it involves three parallel chain reactions that each activate STAT proteins,” Strube said. “My hypothesis is that the relative speeds of these chain reactions are important, and IL6 and IL10 influence the degree to which each is used by the cell.”
An increased understanding of how cells use these parallel chain reactions to produce signal-specific behavior will empower scientists to potentially manipulate the network. They can then create a desired outcome. This research has future applications to medicine and JAK inhibitors, which are used in the treatment of autoimmune diseases like rheumatoid arthritis.
Strube is looking forward to completing this project with her team, and the Intersect Fellowship award will help make that possible.
“This award provides me the time to build my skills, and it’s also a vote of confidence on the direction of my training and research,” she said.