Researchers at Rice University and the MD Anderson Cancer Center have received a $1.3 million 4-year grant from the National Institutes of Health (NIH) to create processes that will clarify the mechanism of the protein networks in cells to drive them. Michael Diehl and Amina Qutub at Rice and Gábor Balázsi at MD Anderson will lead the collaboration to evaluate the mechanisms in cells such as forming their shapes, prompting to change and move, and sometimes evading safeguards to become cancerous.
They will first focus on cytoskeletal regulatory proteins (CRPs) that control how cells take shape and move. The overexpression of these proteins is known to be associated with poor prognosis for some cancer patients, but their mechanisms remain largely unknown. The experiments could offer clues as to why some cells are more prone to turn cancerous than others.
Balázsi’s laboratory has developed the ability to prompt the expression of genetically modified proteins that give the researchers a level of control over CRPs with minimal disruption of other cell functions.
Diehl focuses on the IQGAP protein, which is one of CRPs and controls a cytoskeleton regulating-proteins, to look at the network response and correlate that with cellular behabior. Diehl’s laboratory will view those processes with a multiplexed super-resolution imaging technique that shows each protein molecules in cells in three dimensions, allowing researchers to identify hundreds of multiple proteins at once with precise locating in a cell. They developed techniques to tag, erase and retag proteins to be able to capture much more information comparing to fluorescent dyes with limitation of microscope ability.
Qutub’s laboratory analyzes protein-signaling pathways with sophisticated imaging systems, statistical analysis and computer modelings. The image-processing component allows researchers to pick out dominant cells from a sample of as many as 40,000 within a few hours, she said.
Combined with Diehl’s super-resolution images and Cutab’s multiple analyzing techniques, they will be able to see structures inside Balázsi’s engineered cells in great detail. “The images will give us 50 or 60 metrics that describe what a cell looks like, including chemical signaling,” Qutub said. “This will allow us to rapidly phenotype (or characterize) the cell.”
“We should be able to determine that over time a group of cells will include, say, four dominant phenotypes, or will have certain dynamics,” she said. The technique is promising for clinical biopsies to diagnose or compare patients, or even to see if a person is predisposed to a particular disease, she said. “All these techniques could be applied in the future to patient samples.”