NSF Career Awards
A computational approach to study molecular mimicry in host-pathogen interactions
Certain that too much time had elapsed since applying for an NSF CAREER award, Dmitry Korkin had all but given up hope that his proposal would be funded. The MU assistant professor of computer science in the College of Engineering had heard that first-time applicants most frequently receive encouragement to try again.
Anxious for feedback from NSF on how to make his proposal stronger so he could begin work on a resubmission, Korkin was stunned when he saw NSF’s “congratulations” message pop up in his e-mail.
“I looked at it in disbelief for several minutes. I was scared to assume that’s what it was.” said Korkin.
Not only had he received a CAREER award for his proposed molecular mimicry research focusing on host-pathogen interactions, his entire $613,000 budget had been funded.
When working to computationally predict protein structures, Korkin became fascinated with molecular mimicry. Proteins’ unique three-dimensional shapes, and the way that they connect and interact with one another, dictate functions within the cells of every living organism and are key to all biological processes. But in some cases, pathogens invading host organisms have evolved ways to mimic functionally important parts of the host proteins or even the entire protein structures, in order to bypass the host immune system.
“Research in this area is under-represented in bioinformatics. Host-pathogen systems are hard to study because you need to study two organisms in mutual action,” said Korkin.
Korkin’s research aims to develop methodologies to accurately detect and structurally characterize these virulent mimicries computationally, both in cases where host and mimicry structures are similar, and in instances where a protein has altered only its binding site to gain access to an unsuspecting host.
“We look at all proteins in a pathogenic microbe, attempting to detect which of them get into a host cell,” he explained. “Out of this pool, it must be determined which of them use the mimicry mechanism.”
A variety of microbes across a broad spectrum of human, plant and animal hosts use similar or identical systems, leading researchers to speculate that the mimicry mechanism may be the same in many proteins. Identifying “signatures” of protein binding sites will enhance computational efforts to identify and target pathogen mimics.
“If we can specify which parts of proteins interact with host proteins, we can design a drug and make it attach to the place targeted by the mimic, making it nonfunctional,” said Korkin, addressing one of the potential outcomes. Such a discovery could lead to the cure of infectious diseases like malaria, and may lead to the prevention of such events as catastrophic crop losses due to plant pathogens.
Korkin also is excited about the recognition the project will bring to MU’s Informatics Institute and the bioinformatics program, as well as the meaningful research opportunities the grant provides for the undergraduate and graduate students working with him. His ultimate goal is to make accurate computational predictions and characterizations of host-pathogen interactions available to the broader research community.
“This is a general problem,” said Korkin, talking about how widespread the impact of the research could be, literally making a life and death difference. “This award gives me much more flexibility and confidence in studying my research.”
Jae Wan Kwon
Ultra-sensitive real-time acoustic resonant liquid mass sensor for tag-free disease diagnostic screening
A crucial difference between the biosensor research for which Jae Wan Kwon received a coveted National Science Foundation (NSF) CAREER award and other acoustic resonant sensors is the ability of Kwon’s devices to do highly sensitive real-time mass detection in liquid environments. This capability is an obvious advantage in regard to disease detection in humans, who are roughly 70 percent water.
The assistant professor of electrical engineering in MU’s College of Engineering is working with micro-electromechanical systems (MEMS), tiny devices much smaller than the diameter of a human hair, to detect disease-related substances in body fluids. The sensor he has developed doesn’t require bulky data reading and analysis instruments but can be integrated with equally small circuits, creating potential for small stand-alone disease-screening systems.
Kwon’s work with detecting cancer through the use of micro/nanotechnology began as an interdisciplinary collaboration with an MU biochemistry researcher who was studying breast cancer.
“Many disease-related substances in liquid are not easily tracked,” said Kwon, explaining that in a liquid environment, most sensors experience a general loss of signal quality. “By using highly sensitive acoustic resonators in liquid, these substances can be effectively and quickly detected — a brand new concept that will result in a noninvasive approach for breast cancer detection.”
As a member of the University’s ECE faculty since 2005, Kwon appreciates MU for the numerous potential interdisciplinary collaborations it offers. Since coming here, he has been able to create new micro/nanotechnology facilities in which to pursue his research within an impressively short time — including a “cleanroom” — all on a shoestring budget. His success is largely due to his own talents in procuring — and refurbishing — used equipment. Based on extensive past experience, he has supplemented the instrumentation in his lab with other pieces that he was able to build from parts, saying that he can easily picture in his mind how things work.
A huge baseball fan, Kwon explained his elation at receiving the CAREER award in ball diamond terms: “When I learned the news about the award, I felt I had hit a big home run in the right direction, after feeling like I’d just been hitting big fouls.”
The young researcher’s ultimate goal is to produce a device that will simply and quickly diagnose specific diseases, and could eventually be used to create “point of care” systems. He hopes to someday see his research manifested as simple home kits for easy, rapid and accurate diagnosis of various diseases such as breast cancer and prostate cancer — a research grand slam.