JH is the most versatile insect hormone; it coordinates multiple developmental and physiological processes ranging from molting to aging. Although discovered over 70 years ago, the mechanism of JH action remains unknown. Moreover, despite long-standing efforts and interest, the search for a JH receptor has not been successful. The overall goal of research in the lab is to uncover the molecular mechanism underlying JH action. There are two different projects currently underway in our lab – both of them use the fruitfly Drosophila melanogaster and insect cultured cells, and both involve the combination of molecular genetics and cell biology approaches.

Previously, we identified a group of genes whose expression is induced by JH in Drosophila cultured cells. One of those genes – E75A – encodes the nuclear hormone receptor. E75A is the first known transcription factor that is induced directly by JH. Importantly, we found that JH regulation of E75 gene expression is conserved in mosquito, Anopheles gambiae, and moth, Manduca sexta, suggesting that the function of the E75 gene in JH signaling may be conserved as well. Our first project is on the hormonal control of E75 gene expression. We are working to identify cis-acting regulatory element(s) that confer JH-dependent transcriptional activation of E75. The Drosophila E75A promoter is a direct JH target: (i) it can be activated in the absence of protein synthesis; (ii) it is extremely sensitive to low levels of JH; and (iii) its activation is rapid and shows a decent fold of induction. The additional strength of this project is the use of comparative genomics, approved by our observation that E75 JH-responsiveness is conserved in evolutionary distant species of Diptera and Lepidoptera.

Our second project addresses the biological function of another JH-inducible gene, which is a Drosophila homolog of human ELAC2. ELAC2 is the prostate cancer susceptibility gene. We have found that: (i) Drosophila ELAC2 is an essential gene; (ii) the ELAC2 protein is a part of the tRNA maturation pathway; (iii) ELAC2 has an additional role besides tRNA processing, perhaps involving the cell cycle regulation. Presently, we are using genetic, biochemical, and molecular techniques to understand the role of ELAC2 during development of complex organisms.