In humans, malaria is caused by the parasite Plasmodium, most notably P. falciparum, that is spread by the Anopheles mosquito. Global malaria rates are devastatingly high, so researchers looking to curb transmission have investigated many potential solutions, including genetic engineering.

Since Plasmodium is a parasite, the immune system of every mosquito that carries it tries to attack it, so a stronger immune system leads to lower parasitic survival rates, and therefore less cases of malaria in humans. In December of 2011, a team of researchers released a peer-reviewed research article on their experiments with genetically modified mosquitoes and their resistance to the plasmodium. Previous studies found that a signal transduction pathway for the immune system of mosquitoes, called IMD, is crucial in eliminating plasmodium “in three major malaria vectors, Anopheles gambiae, A. stephensi, and A. albimanus.” The IMD pathway involves a transcription factor called Rel2 that controls the production of TEP1, APL1, LRRD7, and FBN9, some of the most effective immune factors ever found for killing plasmodium before it multiplies in the host organism. To test the role of Rel2 in the immune response to Plasmodium, these researchers created three types of transgenic mosquitoes with over-expression of Rel2, then collected data on their resistance to Plasmodium.

The location of the transgene affected resistance to Plasmodium, but since having multiple copies of the transgene did not differ from having just one, researchers were able to experiment with putting the gene in random places and use a system to find the best combination.

The three types of GM anopheles mosquitoes studied in this experiment were Cp-Rel2, Vg-Rel2, and a hybrid of the two. When a blood meal is taken, it can induce Cp (carboxypeptidase) or Vg (vitellogenin) promoters, which initiate the production of Rel2. In Cp-Rel2, the highest concentration of transcript occurred 6-12 hours after a blood meal, while the parasite was in the mosquitoes’ midgut lumen, and in Vg-Rel2, highest concentration occurred 12-24 hours after blood meal, “when the parasite is reaching the basal side of the midgut tissue.” Experimental results indicated that Cp-Rel2’s more immediate response is favorable to the elimination of Plasmodium, because “[t]he hybrid and midgut-specific (Cp-Rel2) transgenic lines were more resistant to Plasmodium infection than was the fat-body-specific (Vg-Rel2) line.”

Overall, the experiment was a novel success, as infection rates were significantly lower in the GM mosquitoes, especially in the Cyp and Hyb types. The author summary declared that the “transgenic mosquitoes were close to completely resistant to human malaria parasites,” which has huge implications for fighting the painfully high numbers of cases and deaths from malaria every day. As this research continues, more discoveries and applications will be found, and one day this solution might be applied to drastically reduce the countless lives taken prematurely by an ancient disease.

This week’s article is an aberration from the typical Education in Epidemiology post, because instead of recapping an episode of This Podcast Will Kill You, I did some research on GM mosquitoes and ongoing efforts to decrease malaria rates with them. I briefly mentioned these projects in a previous article on malaria, as mentioned in the podcast, but I’m doing a research paper for the Honors program at my school, and I chose to look into these GM mosquito efforts, because it is so fascinating to me. 

This week’s post only features one of the articles I’m including, though I’ll be using at least ten in my paper. I wanted to combine multiple pieces into one article this week, but it took me several hours to just read and comprehend the original article, so you’ll have to wait to find out more. Expect to see more on these skeeters in the near future, though!

Y. Dong, S. Das, C. Cirimotich, J. A. Souza-Neto, K. J. McLean, G. Dimopoulos, Engineered anopheles immunity to Plasmodium infection. PLOS Pathog. (2011).