"We don't really quite understand yet why this happens, but we do know that the mosquito's immune response is totally overamplified," Michel said. "Instead of melanizing parasites or bacteria, the mosquito's body attacks itself, getting melanotic pseudo-tumors throughout it."
These pseudo-tumors appear as black dots on the insect's thorax and abdomen. Afflicted mosquitoes that do not initially die from the tumors steadily lose interest in blood feeding over time.
"So what we're going to do with this grant is to find out which proteases -- since it's most likely more than one -- are being inhibited by serpin-2 for this whole process to occur," Michel said. "Right now we have very little information about the cloud of proteases that float around in the insect, with regards to what they do and how they interact."
Finding the proteases will require lots of detective work as more than 50 proteases are potentially being inhibited by serpin-2. However, Michel said, the most time-consuming portion may be collecting enough material from the mosquitoes to sample, as one mosquito yields about 0.1 microliters of bodily material.
Several co-investigators are also lending their expertise to the study. Michael Kanost, university distinguished professor and head of the department of biochemistry, is helping with expression of proteases and in vitro testing. Christopher Culbertson, associate professor of chemistry, is building microfluidics technology that will allow for better plasma analysis from the mosquitoes, potentially helping with the sample sizes. Scott Lovell, director of the protein structure laboratory at the University of Kansas, will use X-ray crystallography to visualize how serpin-2 binds to the proteases it inhibits.
"By the end of the study we really hope to say serpin-2 is a perfect target for an insecticide that prevents the mosquito's immunity," Michel said. "The ne
|Contact: Kristin Michel|
Kansas State University