Engineering graduate student studies functionality of blood vessels
Story by: Jashin Lin
A video of bright, gently pulsing, irregular green stripes dimly lights up a computer screen in a small laboratory. To the right is a complex-looking construct with racks that takes up most of the available space, and to the left is Srikanth Ella, a doctoral student in biological engineering at the University of Missouri who is developing techniques for imaging blood vessels that may lead to research on preventing heart attacks and related diseases. He is working with Michael Hill, professor of medical pharmacology and physiology, bioengineering and the assistant director of Dalton Cardiovascular Research Center, where the lab is located.
Ella, who studied electrical engineering as an undergraduate in India, explains that the green stripes in the video are vascular smooth muscle cells in blood vessels whose primary role is to regulate contraction and relaxation of the blood vessels. He uses the microscope – the piece of equipment that fills up most of the room – to see, or image, how blood vessels move and contract.
“We want to understand the signaling mechanisms underlying the functionality of blood vessels, particularly arterioles, which form a major resistance pathway to blood circulation,” Ella says, gesturing at the screen, explaining that the cells appear green in the video because he uses a fluorescent indicator to label calcium ions moving around in the smooth muscle cells.
“Blood vessels expand and contract, which is how they regulate blood flow throughout the body,” Ella said. “This phenomena, scientifically know as the ‘Myogenic Response,’ is affected in diseases such as hypertension, which ultimately results in high blood pressure. If we understand the basic functionality of blood vessels, we can help prevent heart diseases.”
Ella and his research group have custom-built a high-speed spinning disk confocal microscope as part of the project. He and other researchers involved with the project have so far been refining their techniques on male rats. Collaborators include Michael Davis, also a professor in medical pharmacology, Gerald Meininger, director of Dalton and faculty from the Medical College of Wisconsin.
“Until now, the accepted technique to measure membrane potential in smooth muscle cells was patch clamp – electrophysiology,” Ella said. “We’re developing new noninvasive technologies to optically image the changes in membrane potential using Fluorescence Resonant Energy Transfer, or FRET.”
FRET can detect membrane potential in multiple cells and, unlike electrophysiology, it can potentially be done in vivo, or in the body.
The upshot of the research is that it may lead to early prediction of heart attacks and heart-related diseases, and pharmaceutical companies can potentially begin to develop drugs to help prevent them. The techniques also can be modified to image other types of body tissues.
Besides the primary microscope in Ella’s lab, he and his team are developing techniques for studying single cells in simulated high-tension environments – similar to that in blood vessels – which is advantageous for the study of cellular signaling pathways at the single cell level.
Ella, who expects to finish his Ph.D. by 2010, received the Clinical Biotective Award sponsored by the National Institute of Health in 2009.
“As part of the award, we take clinical issues from hospital to the bench,” Ella said, using the colloquial term for lab research. “Then, the doctors take the data back for use in developing cures for diseases. In addition, the award encourages the development of biomedical electronic devices for scientific communities.”