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Rice, MD Anderson Win $1.3M to Investigate Protein Networks

NEW YORK (GenomeWeb News) – Investigators at Rice University and the University of Texas MD Anderson Cancer Center have won a $1.3 million grant to use molecular imaging and other tools to study protein networks and protein expression in cells, Rice said today.

Funded by the National Institutes of Health, the project will center on the internal cytoskeleton of stem cells and the proteins that regulate the plasticity that enables these cells to adopt the characteristics of other cells. When these proteins are overexpressed they have been associated with poor prognosis in some cancer patients, although how and why that happens is unknown.

"We want to develop a composite experimental and theoretical approach that allows one to take individual proteins and control their expression level uniformly in a population of cells," project leader Michael Diehl, a professor of bioengineering and chemistry at Rice's BioScience Research Collaborative (BRC), said in a statement.

Having such control would enable the researchers to find out if cells move differently or change shape and characterize the spatial patterning of cytoskeletal regulatory molecules, which together will enable them to discover the sources of the cells' plasticity at the cellular and molecular levels, Diehl explained.

"The idea is that we can manipulate one of the proteins involved in a regulatory pathway so we can trigger cells to become more plastic," added Rice's Amina Qutub, an assistant professor of bioengineering at the BRC.

To manipulate these proteins, the partners will use a technology developed by MD Anderson's Gábor Balázsi that enables prompt expression of genetically modified proteins and will give the partners control over cytoskeletal regulatory proteins with only minimal disruption of other cells.

Diehl will focus this technique on a CRP that tunes cell-signaling responses and controls proteins that regulate the cytoskeleton. The researchers plan to perturb the regulatory network of this protein so they can see how the network's response may correlate with the way cells behave.

Diehl said his team will use a multiplexed "super resolution" imaging technique to view all of these processes. This approach enables researchers to see individual protein molecules inside cells in three dimensions and to identify these proteins and see how they fit into a cellular structure.

His group has developed erasable molecular imaging probes for such studies, which will enable them to tag, erase, and retag proteins and gather "information from snapshots of a cell taken before and after perturbation," the partners said in the statement.

Qutub's group will analyze the protein-signaling pathways by integrating image processing, statistical analysis, and computer models to characterize the processes happening inside of a cell in detail. This processing approach also enables researchers to select dominant cells from a sample with as many as 40,000 cells in a few hours, she said.

Qutub's lab will have 50 or 60 metrics that describe cellular appearance, including chemical signaling, which will help the researchers to rapidly phenotype a cell and then develop computer models that predict how certain types of cells will change after they have been perturbed.