“Hopefully, I’ll convince you…that it is at the intersections of all these very different disciplines that the biggest advances are likely to be made,” said Suresh, who served as dean of the Massachusetts Institute of Technology’s engineering school.
Of course, he noted, these intersections are not new. But recent advances mean “we can now go to the cell level and molecular level and the single DNA level” with great precision, Suresh said. “That, combined with the revolution in genomics and genetics, gives us an opportunity to… ask questions that we may never have asked before.”
One such question is how disease triggers physical changes in cells. Suresh has applied this question to a type of malaria, Plasmodium falciparum malaria, and its effect on red blood cells.
|Suresh (l) enjoys a reception in the NIH Library following his July 25 lecture. With him are Dr. Michael Gottesman (c), NIH deputy director for intramural research, and Dr. Roderic Pettigrew, NIBIB director.
Suresh emphasized the role of computational modeling and simulation in tackling complex biological questions.
Photos: Bill Branson
Usually, red blood cells can squeeze through very narrow blood vessels, but malaria reduces the cells’ flexibility. When measured conventionally, the flexibility appeared to decrease by around 3 to 5 times. Using advanced engineering tools, however, Suresh’s team learned that the cells’ flexibility can, in fact, decrease up to 50 times when probed over the full range of possible stages.
Collaborations provided other insights into malaria, which is responsible for approximately 700,000 deaths each year. Previous research on the flickering, or fluctuations, of red blood cells yielded unclear results, Suresh explained. “The problem was we couldn’t do a full field experiment” to monitor the range of changes, he said. “We decided to fix that.”
Suresh’s team used a technique that is well known in physics but was never applied to biology. Combining laser technology with mathematical equations, the researchers were able to monitor cell fluctuations in the nanometer (or billionth of a meter) range closely in just a millisecond. They could then determine that cells infected with P. falciparum malaria definitely lose their ability to flicker.
Suresh’s team also wanted to visualize malaria’s effect on red blood cells’ ability to flow through the tiny blood vessels of the brain. Therefore, using a tube 1/30th of the thickness of a human hair and a high-speed video camera, the researchers taped the cells’ journey. Healthy cells easily slid through, but malaria-infected cells clearly got stuck.
Such work could play a role in detecting malaria, Suresh noted. “Can we design a device that is the size of a thumbnail [and] carry it to a remote hospital in a developing country where you take a drop of whole blood, put it in this microfluidic device and [find out] if a person has malaria?” The answer is yes, he said, though such a tool might cost a dollar or two instead of the 10 cents he had hoped.
Suresh also emphasized the role of computational modeling and simulation in tackling complex biological questions. Today, for example, computer simulation of a spleen means researchers don’t need the actual organ to explore how it works to remove a parasite.
Suresh concluded by thanking his colleagues and in doing so illustrated the potential reach of interdisciplinary collaboration. His list of coworkers included engineers, biologists, physicists and medical doctors from three different continents.
To watch a videocast of this lecture, go to Past Events at http://videocast.nih.gov.