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Cells do talk to one another, but the question remains how

Inside the human body, an amazing amount of communication occurs constantly. But the dialogue is rather extraordinary. The orators are actually multiple cell types that make up the human tissues. And for biologists, the fundamental question remains as to how these processes occur within the complex environment of tissues and organs.

One avenue of research receiving support to answer this question is the use of systems biology, a field that promotes the study of the cell as a system using several different techniques to acquire information about its physiological processes.

The National Science Foundation's Advances in Biological Informatics program area has awarded a three-year, $1.12 million research grant to three Virginia Tech researchers with expertise in systems biology and tissue engineering: T.M. Murali of computer science, Padma Rajagopalan of chemical engineering, and Rich Helm of biochemistry.

All three are members of the Virginia Tech Institute of Critical Technology and Applied Science's Center for Systems Biology of Engineered Tissues. Rajagopalan directs this center. Murali is the co-director of the center as well as the principal investigator on this new award. Helm is director of the Virginia Tech Mass Spectrometry Incubator, a collaborative resource funded in part by the Fralin Life Science Institute and the biochemistry department.

Rajagopalan is a past recipient of a National Science Foundation CAREER Award to fund her work on studying cell migration in complex environments, and in the past two years she has received more than $1.75 million in funding to create engineered tissues that mimic the human liver.

The liver is the primary organ in the body that metabolizes foreign compounds such as drugs, alcohol, cigarette smoke, and environmental chemicals. The newly funded work will take advantage of Rajagopalan's in vitro three-dimensional liver mimic, an engineered functional tissue that contains two different hepatic cell types in a layered configuration.

Preliminary results from this work have shown that the 3D liver mimics have the ability to simultaneously maintain the observable traits of both hepatocytes, the main cell type in the liver, and liver sinusoidal endothelial cells. The investigators will use the new National Science Foundation award to discover the pathways by which these two cell types may communicate with each other.

Murali explained, "Each tissue or organ is comprised of different cell types, with each cell type responsible for specific functions. Cells exchange signals to maintain their phenotypes and to optimize their functions. When a cell receives a signal, it sets off complex cascades that trigger and modulate the activities of numerous genes and proteins. However, scientists have only partially mapped out these events. The challenge is to identify these pathways without conducting numerous expensive experiments. Through a combination of experimental and computational approaches, the team hopes to provide a more comprehensive picture of inter-cellular signaling.

Rajagopalan compared the research to the following analogy: consider a large city that has several points of entry and a complex network of roads. A number of paths may exist to enter the city and reach downtown. Only limited knowledge exists on how a person reached downtown. For instance, only the last few roads the person traveled on before reaching downtown are known. The question would remain as to how to trace the entire path taken by the traveler.

Murali specializes in solving problems in computational systems biology. Helm's group uses advanced mass spectrometry techniques to explore complex biological problems such as cell-cell communication, focusing on quantification of proteins and metabolites. When combined with Rajagopalan's model system and expertise, the three teams will address the communication processes involved in optimizing phenotypic function in the liver.

By developing innovative and integrated computational-experimental solutions to study inter-cellular signaling, the researchers believe this project will pave the way for advances in inter-cellular and organ-level systems biology.


Contact: Lynn Nystrom
Virginia Tech

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