Manipulation of Mosquito Biology Aim of Halfon Research Project

“This is an exploratory, novel study that will break new ground in the field of mosquito genomics and genetics,” Halfon says.

Malaria mosquitoes (Anopheles gambiae) are responsible for hundreds of thousands of deaths each year. Although scientists know the sequence of the mosquito genome, they have little functional information about what much of that genome sequence does.

“Our work will take important steps toward filling in this crucial missing information,” Halfon says.

“Moreover, if successful, it will demonstrate our ability to functionally annotate the regulatory genomes of all insect disease vectors as they become sequenced without requiring extensive — and expensive — new genome-scale experimental data for each.”

Halfon notes that while all cells in an organism share the same genome, how that genome is used — which genes are turned on or off at any given time, for instance — needs to be tightly regulated. One way this happens is by means of regulatory sequences embedded in the DNA.

“When it comes to disease vectors such as the malaria mosquito A. gambiae, identifying these sequences can provide critical insight both into the basic biology of the disease vector and especially into developing biotechnological means of manipulating their life cycles for their management and control,” Halfon says.

For more than a decade, Halfon has worked with UB’s Center for Computational Research to build a database called REDfly that contains more than 5,600 regulatory sequences for a different insect species, the fruit fly Drosophila melanogaster.

In conjunction with collaborators at the University of Illinois Urbana-Champaign, Halfon’s research team has developed methods for effective computational discovery of regulatory sequences using Drosophila as an experimental model.

They have demonstrated that existing data from Drosophila can be leveraged to discover gene regulatory sequences in other insects as diverse as mosquitoes, beetles, bees and wasps.

The researchers aim to apply these methods to discover and validate regulatory sequences relevant to disease vector biology and insect biocontrol in A. gambiae to gain a much deeper collection of mosquito regulatory elements.

“Importantly, we will not only predict regulatory sequences, but we will confirm our predictions directly through construction and analysis of genetically engineered mosquitoes,” Halfon says.

The in vivo mosquito work will be performed in collaboration with David O’Brochta, PhD, at the University of Maryland.

The two-year NIAID grant totals $449,000. The agency conducts and supports research worldwide to study the causes of infectious diseases and develop better means of preventing, identifying and treating them.

Halfon’s research will be bolstered by continued development of the REDfly database through a four-year, $1.2 million grant from the National Institute of General Medical Sciences.