"Juvenile hormone (JH) is a critical regulator of insect development. JH prevents juvenile to adult transformation (metamorphosis) until a larva attains a proper size, at which time a drop in JH titer permits adult morphogenesis. Therefore, JH treatment of final-stage larvae blocks metamorphosis and perpetuates their juvenile state. This status-quo effect is significant for use of JH mimics, such as methoprene, for insect pest and disease vector control. Despite considerable effort, the molecular mode of JH action remains obscure due to failure to identify a JH receptor (JHR). In 1986 a Drosophila mutant screen yielded a candidate JHR gene, Methoprene-tolerant (Met). Our recent discovery that Met regulates insect metamorphosis in response to JH inspired new efforts to characterize the JH signaling pathway. This proposal aims to complete the quest for the JH receptor by resolving the structure of the Met protein and by functionally characterizing proteins that together with Met may form an active JHR. The Applicant is experienced developmental biologist and molecular geneticist. However, neither he nor his host institution in the Czech Republic possess the expertise and equipment required for protein structural analyses. Therefore, the Applicant proposes to collaborate with the Australian CSIRO, where a research team led by Prof. Ronald J. Hill has the most relevant experience in resolving the structure of insect nuclear hormone receptors. The team has extensive protein purification and crystallization facilities and access to the Australian synchrotron. The Applicant would greatly profit from the capacity present at CSIRO by learning the approaches to protein expression, purification, and structural analysis. This would not only lead to the above scientific aim but tremendously improve the qualification of the Applicant upon his return to Europe. At the community level, it would increase the lost competitiveness of European-based science in the field of JH research."
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