Newswise — It looks like a neon light show-- pink, blue and magenta squiggles dancing in the darkness. These are not just pretty pictures, but protein receptors interacting within the membrane of a living cell. And to South Dakota State University cell biologist Shalini Low-Nam, they are an incredible sight and possibly an important step in understanding how diseases such as cancer affect the cells.
“This is something that could not be done five or 10 years ago because the tools to do it did not exist,” said Low-Nam, a postdoctoral research associate in the chemistry and biochemistry department. It was the unique tools available in assistant professor Adam Hoppe’s laboratory that drew Low-Nam to SDSU in October 2011 after completing her doctorate in biomedical sciences at the University of New Mexico.
In recognition of her potential as a researcher, Low-Nam has earned the prestigious National Institutes of Health Ruth L. Kirschstein National Research Service Award, which will support her work for the next two years.
“This fellowship recognizes her potential as a future leading scientist,” said Hoppe. “I am incredibly fortunate to have her in my lab.”
Low-Nam’s work will focus on a protein receptor called the macrophage colony stimulating factor or MCSF receptor, which controls the growth and development of the macrophage, a type of white blood cell. Macrophages serve as one of the body’s defense mechanisms, Low-Nam explained. For her study, a lab technician takes bone marrow from mice and then allows them to mature into macrophages because they serve as a good model for human macrophages. “Macrophages go in and out of the blood to search out bacteria and viruses that require removal,” she said. When they find them, they eat and digest the bacteria and other pathogens, thereby removing them from the body. This transdisciplinary research is aimed at understanding the biochemical pathways in cells, Hoppe explained. Low-Nam will integrate ideas from chemistry, mathematics, physics and optics. “She’s an expert on this,” said Hoppe, “and an up-and-coming leader in the field.”During her doctoral program, Low-Nam worked with single particle tracking, which looks at the motion of individual particles or molecules within the cell and its environment. She will combine this with other fluorescence-based strategies that allow her to tag specific proteins with substances and make them glow.
The lasers on Hoppe’s microscope then light up the fluorescent tags on the protein receptors, so she can see how they interact with one another and the cell membrane. This one-of-a-kind microscope lets her view as many as four different molecules at once, Low-Nam explained.
Low-Nam wants to determine how the interactions between the MCSF receptor and other proteins are influenced and regulated by the cell membrane.
“Imagine the membrane as a mosaic of components—proteins, lipids and sugar—that allow the cell to function,” Low-Nam said. “The cell communicates outside to inside through the proteins that span the membrane.”
After tagging each protein with a different fluorescent color, Low-Nam uses the microscope to take sequential images of how proteins cluster on the cell surface in a process called signaling. Eventually, the membrane will fold inward and pinch a section into the macrophage to remove the proteins from the surface. As she watches the neon light show, she takes measurements of what’s happening, noting the curve of the membrane and the interaction of the proteins. Biologists visualize this signaling as a linear sequence, Low-Nam explained, but this has not been verified because no one has ever recorded this happening. “Is this characteristic of the process or just one of many ways this can occur?” Low-Nam asked. “What signals the cell to take in specific proteins?” These are questions she seeks to answer.
“By understanding how these dynamics occur in normal macrophages, we can try to decouple what happens in the case of disease,” Low-Nam said. When a genetic abnormality or mutation affects the MCSF receptor, it changes the cell’s behavior. “This interference allows disease to get a hold of the cell,” Low-Nam explained. Because this is basic research, no specific disease has been targeted, Low-Nam said, emphasizing that her work analyzes the fundamental mechanism of cell growth at a molecular level.
However, the receptor she is studying has been implicated in acute leukemia because it regulates cell growth, Low-Nam said. “Cancer is uncontrolled growth of cells.”
If all goes well, one day her observations of these neon proteins dancing in the night may give scientists the information they need to combat leukemia and other diseases.
About Adam Hoppe’s Cellular Biochemistry Lab in SDSU’s Department of Chemistry and Biochemistry
Our lab uses a suite of biochemical and fluorescence imaging based approaches to interrogate the molecular interactions of cellular signaling. Specifically, we focus on understanding how fundamental signaling and their alterations in macrophages, important cells of the immune system, result in leukemia and other diseases.
About South Dakota State University
Founded in 1881, South Dakota State University is the state’s Morrill Act land-grant institution as well as its largest, most comprehensive school of higher education. SDSU confers degrees from eight different colleges representing more than 175 majors, minors and specializations. The institution also offers 29 master’s degree programs, 12 Ph.D. and two professional programs.
The work of the university is carried out on a residential campus in Brookings, at sites in Sioux Falls, Pierre and Rapid City, and through Cooperative Extension offices and Agricultural Experiment Station research sites across the state.