Pradipsinh Rathod welcomes scientists of all disciplines to malaria research.After Tanzanian-born Pradipsinh Rathod completed his PhD 15 years ago, he wanted to work on a disease relevant to developing countries. He picked malaria because it kills over a million people a year, primarily children under five in sub-Saharan Africa.
In the beginning, he says, it was hard to get a good academic job doing malaria research. "Even parasitologists looked down on it as a difficult system, and not the one you would pick if you were trying to make a career in academia," says Rathod, now professor of the department of chemistry at the University of Washington, Seattle.
The professional outlook for malaria researchers began to change six years ago when four groups got together to sequence the human malaria parasite, which was divvied up chromosome by chromosome among them. And it should change even more now that researchers have at their disposal the genomes of all three organisms involved in the transmission of malaria — the parasite Plasmodium falciparum (see page 498, this issue) and its mosquito vector Anopheles gambiae (Science 298, 291; 2002; see box opposite), and the human host, published last year (see Nature 409, 860–921; 2002).
This information should help identify the genes and pathways involved in the transmission, pathogenicity and drug responses of malaria, and provide a greater understanding of the complex host–parasite and host–vector interactions. In the longer term, it may reveal new targets for drug development, better targets for vaccines and new ways to interrupt malaria transmission. Funding — although still modest compared to some other pathogens that affect both the developing and developed world — is up, and prospects for a career in malaria research have never looked better.
RETOOLING
The metamorphosis of Rathod's lab, following the release of the raw sequence data, is illustrative. He is completely retooling his lab set-up.
Five years ago, his lab consisted of a bunch of individual scientists, each working on a different gene or a different drug. "We would work endlessly on trying to express a particular protein in abundant amounts and trying to look at the kinetics of binding of a particular drug to a protein," he says. Now, using microarray technology, for example, it is possible to look at gene expression in the whole organism rather than just individual genes
As a result, students are now trained more broadly. In Rathod's lab, for example, they would learn some cell biology, molecular biology, organic synthesis, bioinformatics and computer science. This, he says, better prepares them for what's going on — not just in malaria but in many other multidisciplinary fields as well. Moreover, he says, "the field is incredibly welcoming of the types of scientists that we didn't interact with a lot before, such as engineers, computer scientists and organic chemists".
In his department, he says, even people doing work on nanotechnology and microfluidics are becoming interested in malaria. In one example, researchers are developing imaging technologies that they hope will allow them to visualize individual malaria molecules in live cells, and characterize the shape and deformation of infected host cells. And when recruiting, he looks for people with expertise in combinatorial chemistry, as well as in skills used to study nucleic acid–protein interactions and genome-wide responses of cells to drugs.
CHANGING RESEARCH CLIMATE
The funding climate indicates that these changes won't just be limited to Rathod's lab. Funding for malaria research by the US National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID), for example, increased fivefold between financial years 1991 and 2001 (US$10.4 million and $57.8 million, respectively) and is estimated to reach $72.1 million in 2003. The P. falciparum genome project was completed with funds from both public (NIAID and the US Department of Defense) and private (Burroughs Wellcome Fund and the Wellcome Trust) sectors.
The Seattle-based Bill and Melinda Gates Foundation has also supported research in this area, so far contributing more than $125 million to malaria research. This includes $50 million over ten years to the Malaria Vaccine Initiative at the Program for Appropriate Technology in Health (PATH) in Seattle and $40 million over five years to the London School of Hygiene and Tropical Medicine in Britain for the creation of a new malaria centre.
Another promising new initiative, made possible by a $100 million gift from an anonymous donor, was the creation in May 2001 of an institute dedicated solely to malaria research within the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. The Johns Hopkins Malaria Research Institute will bring together experts from a variety of disciplines — entomology, parasitology and bioinformatics — who are interested in revisiting issues from a basic-science point of view yet are squarely focused on the goal of developing new treatments and preventive measures for malaria.
Nirbhay Kumar of the new Johns Hopkins Malaria Research Institute sees great opportunities ahead.The institute has already sparked "tremendous interest", and not just from people in the field, says Nirbhay Kumar, professor of molecular microbiology and immunology at the new institute. Three new faculty have already been hired (two more offers are pending), and he expects to recruit five more over the next few years in the areas of bioinformatics, cell biology, immunology, structural biology and vector biology. There will also be fellowship money for training young students and postdoctoral fellows, as well as seed money for pilot projects that bring in people from elsewhere in the university who have never worked on malaria before.
The availability of the genome sequences "is going to open up tremendous opportunities for people to jump into an exciting and very challenging area", says Kumar, who has been at Johns Hopkins since 1986 and has worked on malaria for 20 years. Originally from India, he has focused on the biology of malaria transmission and the development of better targets for transmission-blocking vaccines. He recalls a time when, as a postdoctoral fellow, he spent more than a year just trying to clone a gene — "a gene that I can get pretty much overnight" now that the sequence is available.
The field is "wide open", he says. "The challenge is again upon scientists to make use of this information and learn from it and try to outsmart the parasite that has been outsmarting human endeavours so far."
The Bill and Melinda Gates Foundation
http://www.gatesfoundation.org
Wellcome Trust
Burroughs Wellcome Fund
The Johns Hopkins Malaria Research Institute
http://www.jhsph.edu/Dept/MMI/Malaria_Research_Institute/
London School of Hygiene and Tropical Medicine
Malaria Vaccine Initiative at PATH
Mosquito genomics takes off
Now that the sequence of Anopheles gambiae, the mosquito vector of the malaria parasite Plasmodium falciparum, is available, entomologist Peter Atkinson of the department of entomology at the University of California, Riverside, couldn't be happier. He works on mosquito-vector biology, developing genetic strategies for the control of insects that transmit malaria and other diseases.
The sequence gives researchers the ability to look through the whole genome for genes that are essential for pathogen transmission through the mosquito, such as those involved in blood feeding in female mosquitoes.
When asked how his lab is coping with the torrent of sequence information flowing from the genome sequencing projects, he quips: "Well there are more computers than there used to be". Atkinson's lab is made up principally of molecular biologists and geneticists and, when recruiting, he now looks for people with more computational skills than ever before. If they can also write code, that's a bonus.
