The marriage of computer modeling, biophysics and immunology has landed a University of Central Florida scientist more than $1 million in funding for her work, which could have profound benefits in the search for cures to cancer and heart disease.
UCF assistant professor Annette Khaled is conducting research into what triggers the "death protein." The "death protein" BAX appears to annihilate surrounding cells. If its secrets could be unlocked and controlled, it could be a key tool in saving lives.
By identifying one of the mechanisms that leads to the fragmentation and ultimately death of the cells of the immune system, Khaled hopes to develop a peptide-based therapeutic approach that can be used to either stimulate the death of diseased or cancerous cells or protect cells whose inappropriate death causes heart disease or brain damage.
Khaled has put together a team of researchers at UCF with a variety of backgrounds to conduct the research.
"The NIH is making an effort to foster interdisciplinary research," Khaled said because biomolecular research is so complicated. Teams, which use the strengths of a variety of disciplines to study cell function have an edge compared to those who stick with one expertise and traditional methods.
"Biophysical approaches and computational modeling methods helped us 'see' what is happening biologically," Khaled said.
When she arrived at UCF in 2002 she identified UCF biophysicist, Suren Tatulian, as having the biophysical "know how" to help her understand how proteins interact with membranes. UCF protein chemist, Thomas Selby, has the computational modeling skills that could help her design new biological experiments.
Together, the three scientists discovered that the occupancy of a prominent hydrophobic groove within the molecular structure of BAX could be the key to controlling the protein's lethal activity.
Khaled has studied the inner workings of BAX, a protein that among its activities mediates the death of cells, since her days as a post-doctoral scientist at the National Cancer Institute (NCI) more than five years ago. In 2003, she received $466,000 of National Institutes of Health (NIH) funding in the form of a career development award to study how BAX is activated to cause the death of immune cells. Instead of answers her diligent analysis, employing traditional biological techniques, revealed more questions. In order to crack the BAX "puzzle" and find those elusive answers, she needed a new approach. Khaled found that approach in a partnership that was originally created to help train UCF graduate students in biophysics and computational modeling of protein structure.
In addition to receiving a $1 million grant from NIH, Khaled, Tatulian and Selby have submitted two manuscripts on the joint work - one describing the computer modeling side and the other focusing on the biological findings.
Khaled has also received $919,000 from the NIH for a related study on the function of an immunological signaling protein known as Interleukin 7 that supports the body's immune system to fight off infections and when aberrantly expressed could also underlie the development of cancer.
"Dr. Khaled is truly an outstanding Florida researcher to compete with the best in the country and win," said Pappachan Kolattukudy, director of the Burnett School of Biomedical Sciences in the College of Medicine. "We are fortunate to have her as part of our team, making significant strides in our search for cures to some of the world's most common and deadly diseases."
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