By Phil Williams
University of
Georgia

A team of University of Georgia scientists has discovered 35
genes that contain important regulatory peptides in the malaria
mosquito. The new information could point toward ways to control
the disease, which kills millions of people worldwide each
year.

Included in the 35 are five genes that encode insulin-like
peptides that probably have pivotal roles in the life cycle of
the Anopheles gambiae mosquitoes. Being able to interfere
with the action of these genes on a large scale could keep the
mosquitoes from passing on parasites that cause malaria.

“It’s important to know as much as possible about how these
insects transmit malaria,” said Mark Brown, an internationally
known mosquito biologist at UGA. “These genes offer new
information on the regulatory processes that make the
transmission of disease possible.”

The research was published in the journal “Science” and was
funded by the National Institutes of Health.

Research team

Other researchers involved are Joe Crim and Stephen Garczynski of
the UGA department of cellular biology; Michael Riehle, an
entomologist, like Brown, from the UGA College of Agricultural
and Environmental Sciences; and Catherine Hill of the University
of Notre Dame.

Malaria is one of the planet’s deadliest diseases. It is one of
the leading causes of sickness and death in the developing world.
According to World Health Organization statistics from the late
1990s, 300 million to 500 million clinical cases of malaria each
year result in 1.5 million to 2.7 million deaths.

Children aged 1 to 4 are the most vulnerable. Malaria is
responsible for as many as half of the deaths of African children
under age 5. It kills more than 1 million children — 2,800 per
day — each year in Africa alone. In regions of intense
transmission, 40 percent of toddlers may die of acute malaria.

Peptides govern reproduction

Anopheles, the African malaria mosquito, develops fast in water.
Its reproduction cycle begins with successive blood meals from
humans. Regulatory peptides acting as neurochemicals and hormones
govern these processes, so describing and understanding these
peptides are crucial steps toward control.

“At this point the exact function of these genes is speculative,”
said Crim, a peptide-reception biologist. “None of these
regulatory peptides was previously known for Anopheles. But their
importance is clear.”

The new study is part of an announcement made this week of a
functional completion of the genome for Anopheles gambiae. The
achievement, by a number of labs, could have an enormous impact
on future control of the Plasmodium parasites with which these
mosquitoes infect humans with malaria.

Bioinformatics

The UGA team used bioinformatics — the study of gene databases
on computers — to determine peptide-encoding genes in the
Anopheles genome.

Of particular importance was the revealing of five insulin-like
peptides. The scientists followed intriguing hints that
Plasmodium appears to use insulin from either the female mosquito
or the vertebrate blood meal for its own development, metabolism
and reproduction.

The importance of that connection could be crucial to
understanding how the parasites are passed to humans and create
disease.

“Since most peptide types exist as single-copy genes, each is a
target for genetic interference,” Brown said, “both to unravel
regulatory functions and in the long-term to engineer Anopheles
where it is less hospitable for Plasmodium.”

More genes?

Crim said the computer program looked for genetic sequences and
found candidates for regulatory genes. There may well be more
than the 35 the team found. But these are the most obvious and
first targets for intervention.

The completion of the A. gambiae genome is crucial to scientists.
But more in-depth knowledge is needed before they can find a way
to make the mosquitoes less likely to deliver the parasites that
cause malaria.

To this end, the UGA scientists have begun cloning and expressing
the genetic sequences. They will soon be able to determine their
precise regulatory function in the mosquitoes, along with the
receptors that allow the parasites to infect humans.