Building On Past Discoveries
Linhardt and his collaborators were the first to discover the link between the spread of malaria in humans and heparan sulfate in 2003. In that earlier study, Linhardt compared the receptors in the liver of humans to those of rodents. The liver is the first organ to be infected by the malaria parasite in mammals. The researchers found that heparan sulfate in the human liver was the unwitting transporter of the disease to the human bloodstream. The receptor found in rodents was a different heparan sulfate.
The next step for Linhardt, outlined in the current research, was to determine if heparan sulfate was also present in the species of mosquito known to spread malaria to humans, Anopheles stephensi. To make this key link, Linhardt and his current research team, which includes Rensselaer doctoral students Melissa Kemp and Jin Xie, enlisted the help of New York University physician and entomologist Photini Sinnis. Sinnis and her team at NYU provided their entomological expertise and the mosquitoes needed for the experiments.
After finding heparan sulfate in mashed mosquitoes, the researchers needed to determine if heparan sulfate was in the mosquito organs known to host the malaria parasite. If so, it was likely that heparan sulfate was the reason malaria spreads from mosquito to human and human to mosquito.
In mosquitoes, the malaria parasite infects the digestive tract. A mosquito bites a human who carries the malaria parasite in his or her bloodstream. The parasites move into the bug’s gut and then to their salivary glands, allowing the mosquito to infect another human during its next blood meal. To isolate a two-microgram salivary gland and the four-microgram digestive tract from each mosquito required the extreme skill of Sinnis and her team, which included Alida Coppi. Once isolated, the guts and glands were analyzed by internationally renowned microanalysts Toshihiko Toida, Hidenao Toyoda, and Akiko Kinoshita-Toyoda at Chiba University in Japan. Heparan sulfate was found in both mosquito organs.
As a final step, the Rensselaer team proved that the heparan sulfate in the mosquito bound to the same malaria parasite that heparan sulfate found in the human liver did. It was an unfortunate perfect match.