UC Davis microbiologist aims to eliminate malaria by genetically engineering mosquitoes that are resistant to malaria parasites
For UC Davis faculty member Shirley Luckhart, the road to her present area of expertise — malaria — began back when she was an undergraduate at the University of Florida curious about wildlife diseases. She honed that interest at Auburn University by studying disease agents transmitted by ticks. But her master's thesis wasn't on malaria.
It was on Lyme disease.
Her doctoral dissertation, at Rutgers University, also had nothing to do with malaria.
"It was about invertebrate innate immunity," said Luckhart, today an associate professor of medical microbiology and immunology at UC Davis Health System. "It was about understanding how pathogens inside insect hosts affect the innate immune system of the insect."
That might sound esoteric, but potentially it had relevance to human disease. Understanding how insects put up with pathogens, after all, might shed light on how humans can do the same thing.
"Pathogens and insects have evolved with each other for millions of years," Luckhart explained. "Insects are impacted (by pathogens), but the insect-pathogen association has come to more of an equilibrium. We haven't had so much time, hence we get sick."
Looking back on it, the 42-year-old Luckhart — who last month gave a presentation on malaria in Africa at a Malaria Awareness Day symposium on the Davis campus — saw where her studies were leading.
"I was developing the skill set to address the questions I now want to address with malaria."
— Shirley Luckhart, associate professor of medical microbiology and immunology
She finally started zeroing in on the disease as a post-doctoral researcher in the 1990s, when she did a stint at Walter Reed Army Institute of Research on a fellowship from the National Research Council. Given the U.S. Army's history as a leader in infectious disease research — the anti-malaria drug mefloquine was developed by military scientists — the center proved the perfect training ground for a budding malaria researcher.
Her involvement with the Army led her to Africa, where from 1999 to 2001 she took part in a research project in Kenya on the genetic makeup of malaria-carrying mosquitoes.
"We were looking at whether you could associate genetic polymorphisms in mosquitoes with parasite infection," Luckhart recalled. "Could we show that some genotypes of mosquitoes were more likely to be infected with malaria parasites than others?"
The answer, it turned out, was yes. Luckhart and her colleagues not only characterized a particular gene as playing an important role in the immune system of mosquitoes, they realized that a variation in that gene was associated with malaria parasite infection in mosquitoes they had collected out in the field.
This was an important step toward something that is being fervently worked on today: producing genetically engineered mosquitoes that are resistant to malaria parasites.
"The idea is that when mosquitoes pick up malaria parasites in a blood meal from humans, they kill the parasites rather than spreading them," Luckhart said.
Because of the expense involved, it's controversial work. So is the effort to develop a malaria vaccine, which Luckhart said is at least 10 to15 years away. Simpler, less expensive options include insecticide-treated bed nets and anti-malaria medications. But given economic and political conditions in Africa, there have been persistent problems distributing the drugs and the bed nets where they are most needed and then educating people about their proper use.
"We need to get people to use the drugs properly," Luckhart emphasized. "That's a big reason for drug resistance."
Satya Dandekar, professor and chair of medical microbiology and immunology at UC Davis, was the person who brought Luckhart to Davis in 2005. She said she was struck by her strong background in vector-borne diseases, and the promise that held in terms of malaria research.
"She is unraveling the mechanisms by which the mosquito immune response determines the transmission of the malaria parasite to the human host," Dandekar said.
Gregory Lanzaro, director of the UC Mosquito Research Program and the UC Davis Center for Vector-borne Diseases, said Luckhart was unusual in that she not only "knows the insect, the mosquito, she knows its biology."
"She's done work in the field looking at how mosquitoes behave in nature. And on top of that she's become a competent molecular biochemist. Typically, molecular biochemists know little about the biology of the whole organism."
Lanzaro and Luckhart are members of the UC Malaria Research and Control Group, which includes 21 scientists from five UC campuses. The two are in the early stages of a five-year federally funded project to train scientists at the University of Bamako, Mali, on strategies to combat malaria, a leading cause of death in the West African country.
Luckhart is also working with a researcher in Colombia, where in the Amazon jungle no fewer than 20 species of mosquitoes transmit malaria compared to essentially one in sub-Saharan Africa. Since it's impossible to distinguish between the insects visually, the pair is seeking to develop rapid genetic tests to identify species and determine whether they are infected with the parasites.
"There are limited resources in Colombia for malaria control," Luckhart said, "so rapid diagnostic tests could help us identify the villages most at risk."
Finally, in her Davis laboratory, Luckhart is delving ever deeper into the mystery of how malaria-carrying mosquitoes manage to live with malaria parasites. Among other things, she's trying to understand a phenomenon known as "crosstalk" in which factors derived from human blood, such as insulin and certain proteins, influence mosquito immune responses.
Just like her work 10 years ago in Africa, this line of research has implications for developing genetically altered mosquitoes.
"If we want to produce a genetically engineered mosquito that kills malaria parasites," Luckhart said, "we'd better know how they kill the parasites."