How the brain works is an important and complicated question. One of the many functions of the brain is to regulate behavior, such as social interaction among individuals, which, in turn, determines success in courtship and mating. It is known that behavior is guided by both genes and the environment, and that the influences interact closely. Brain function also is regulated by hormones in ways that are not well understood. This project studies such hormone-like factors and their influence on the behavior of fruit flies, a model organism for which there exist superb genetic and molecular tools. The genetic and molecular accessibility allows for easier examination and manipulation of these factors. As part of this project, flies that lack genes hypothesized to code for specific hormone-like factors are generated, and the effect on the fly's behavior is documented, to elucidate the relation between the hormone-like factors and behavior. The project also examines another important question: How do these factors pass through the blood-brain-barrier, a cell layer that protects the brain in most higher organisms, including humans. These studies will give new insight into the ways by which hormones circulating in blood communicate with the brain, and how this specific route of blood-brain communication influences behavior. Ultimately, they will help to better understand how the brain works. These studies are being performed at one of the most diverse universities in the United States with a large student body, a large fraction of which comes from underrepresented groups. Both undergraduate and graduate students participate in the research and receive intensive training in the scientific process.
The overall goal of these studies is to examine how complex behaviors are regulated on a molecular level using the well-defined courtship behavior of male Drosophila as a model organism. It is known that gender-specific brain circuits are required for male courtship; however, successful execution of the behavior also requires modulation of these circuits. Circulating factors and hormones are an important part of this modulation. The present studies are based on the recent discovery that the blood-brain-barrier plays an active role in this process. The studies described here explore how specific signaling at this humoral-brain interface modulates courtship. Specifically, the focus is on a nuclear receptor expressed preferentially in males as a link between the action of the two major insect hormones Ecdysone and Juvenile Hormone. Conditional genetic manipulations are used to manipulate signaling through this protein-hormone network exclusively in the blood-brain-barrier. Findings that blood-brain-barrier cells are a site where integration of hormonal effects occurs have the potential to extend in significant ways appreciation of this tissue beyond its barrier function.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
