In public lecture at MIT, former dean describes progress in understanding malaria. Although engineering has long played a key role in developing technology for diagnosing and treating human disease, it has only recently started to have an impact on understanding the cellular and molecular basis of disease. In the past decade or so, engineers have started making major contributions to understanding diseases such as malaria, hereditary blood diseases and cancer, according to Subra Suresh, former dean of MIT’s School of Engineering.
In a talk at MIT on Thursday, Dec. 9, Suresh, who is on leave as the Vannevar Bush Professor of Engineering at MIT and is now director of the National Science Foundation, outlined several ways in which interdisciplinary research has led to new understanding of human disease, especially malaria.
Suresh was chosen to give the first David B. Schauer Lecture, established to honor the MIT professor of biological engineering, who died in June 2009. Schauer devoted his career to the study of bacterial diseases, with a particular focus on understanding how bacterial infection in the gastrointestinal tract leads to conditions such as inflammatory bowel disease, hepatitis and cancer.
Suresh’s achievements in bringing an engineering perspective to the study of human disease made him an obvious choice for the lecture, said James Fox, professor of comparative medicine and biological engineering, who introduced Suresh. “His discoveries regarding the connections between nanomechanics and malaria have shaped new fields at the intersection of traditional disciplines,” said Fox.
Suresh, who has held appointments in MIT’s Departments of Materials Science and Engineering, Biological Engineering, Mechanical Engineering and the Division of Health Sciences and Technology, first became interested in studying infectious diseases about eight years ago.
“The perspective an engineer can bring to seemingly disparate fields such as infectious disease can be very beneficial in trying to not only understand the mechanisms of human infectious disease, but also developing new technology for diagnostics and therapeutics,” Suresh said.
A new view of malaria
As an expert in nanotechnology, Suresh decided to study how mechanical changes at the cellular level can influence human disease. Specifically, he focused on understanding how the malaria parasite alters both the stiffness and stickiness of red blood cells, which prevents red blood cells from delivering oxygen to all body tissues.
Malaria infects about 400 million people worldwide every year, and kills between 1 million and 3 million. Two parasites — Plasmodium falciparum and Plasmodium vivax — widely cause the disease, but Suresh has focused on P. falciparum because it is both deadlier and amenable to culture in the laboratory.
Malaria is transmitted by mosquitoes, which release the parasite into the human victim’s bloodstream as they feed. After reproducing in the liver for several days, the parasites enter red blood cells, where they repeatedly undergo a 48-hour life cycle. At the end of each cycle, more parasites are released to infect additional blood cells.
Using “optical tweezers” (a technique that involves gently stretching cells with two beads controlled by lasers), Suresh and his colleagues discovered in 2005 that after P. falciparum invasion, red blood cells become up to 100 times stiffer than healthy red blood cells, much more than previously thought. This loss of deformability can greatly impair the cells’ ability to flow through tiny capillaries. They later quantified how infected red blood cells have a much greater tendency to stick to one another and to the walls of blood vessels, making them clump together.
Together, those two biomechanical changes can dramatically reduce the amount of oxygen reaching many tissues, prompting victims to suffer typical malaria symptoms such as anemia, headache and muscular fatigue, and potentially kidney failure or death.
More recently, Suresh collaborated with physicists in MIT’s George Harrison Spectroscopy Lab to show that malaria infection also causes red blood cell membranes to lose their ability to vibrate. Those vibrations, which are indicators of a cell’s health, had previously been impossible to study for the entire cell because they are measured in billionths of a meter and occur in just microseconds.
Suresh and colleagues are now studying the role of a particular protein that appears to control the deformability changes in red blood cells. Their work could lead to new drugs that target the protein, such as RESA.
All of these studies were made possible by the development of new technology, such as optical tweezers, microfluidics and application of technologies not traditionally applied to biological systems, such as the microscopy techniques used in the MIT Spectroscopy Lab. “Most of the things we’ve been able to do could not have been done 10 years ago. The experimental and computational tools did not exist,” said Suresh.
Suresh said he hopes those types of interdisciplinary studies will become more widespread, at MIT and elsewhere. Fields such as genetics, nanotechnology, microfluidics and computational engineering have much to offer the study of human disease, he said. “We have the opportunity to find something new and unique.”