The nervous system controls human and animal behavior. From behavioral analysis, neuroscientists can gain insights into brain function such as learning, memory, decision-making and other cognitive activities. Yet, the neural mechanisms by which behavior is produced and regulated remain poorly understood. Dr. Zhang and his associate propose to develop a new molecular genetic method to non-invasively dissect the neural circuitry underlying behavior in the fruit fly, Drosophila melanogaster. They will be developing and refining a genetic method that allows for restrictive expression of genes in subsets of neurons in the fly brain. They will then examine the behavioral consequence following the perturbation of these neurons or a neural circuit. This brain-behavior mapping effort is expected to significantly advance the understanding of brain function. Another important aspect of this proposal is to develop new genetic tools. Dr. Zhang has begun and will continue to make these reagents freely available to the fly community. These reagents will be deposited in a public domain (such as the Bloomington Drosophila Stock Center). The strategy developed in the proposed work is also expected to be applicable to other genetic model organisms. This proposal has strong outreach and broader impacts. Building upon the past record of excellence, Dr. Zhang will actively participate in education, training, and outreach to local communities. This includes mentoring undergraduate and graduate students, training a postdoctoral fellow, involving a local high school science teacher in summer research, and participation of science outreach activities in local schools and museums.
In order to fully understand the whole brain, it is essential to understand its parts and their massive connections. At present, Gal4-UAS is the most commonly used method for brain-behavior studies in fruit flies. However, this method has major limitations for behavioral studies because Gal4 expression is usually too broad to be correlated precisely with behavior. Intellectual Merits: To overcome this hurdle, Dr. Zhang and his associates developed a new Flippase-based circuit-mapping method in the fruit fly Drosophila. This line of research employs a genetic method of disrupting circuits and allowing noninvasive ‘lesion’ analysis in subsets of a defined circuit in flies. Since the publication of the new method (called FINGR) it has significantly advanced neural circuit mapping. The FINGR method identifies important structures for which one has no prior knowledge or understanding. Furthermore, the FINGR method has broad applications to neuro- and cell-biological research in Drosophila and should also be readily adoptable to other genetic model organisms. Finally, Dr. Zhang and his associates have produced a large collection of enhancer-trap Flippase transgenic lines which can be used for reproducible refinement of Gal4 expression into smaller units. Dr. Zhang has deposited the key reagents into the Drosophila Stock Center and freely shared this resource with fly colleagues. Many labs are now using the FNGR method or Flippase lines for their research. Broader Impacts: This proposal has significant broader impacts beyond its intellectual innovation. Dr. Zhang has demonstrated a strong commitment to science education and to public outreach and maintained an excellent track record of mentoring women and students from underrepresented groups. His recent mentees include a Hispanic woman postdoc, a Native American woman postdoc, a Native American research associate, 62 undergraduates and a current Hispanic woman graduate. Of these undergraduate students, 36 were women and undergraduates appeared 65X as co-authors (25X on papers and 40X on abstracts). Dr. Zhang also has a long history of designing and teaching science laboratory courses, including Neurobiology Lab and summer courses at Cold Spring Harbor and Woods Hole. In addition, he endeavors to bring educators into his lab to teach science, which is exemplified by his participation in the Science Institute for Elementary School Teachers Program and by his assistance to a female Hispanic Professor and her undergraduate students from Southwestern Oklahoma State University, a primary teaching college in rural Oklahoma. Dr. Zhang has also participated in "brain awareness" (since 2000) and "Science in Action" (since 2007) activities each year to reach out to local communities and schools. At MU, Dr. Zhang will continue these outreach activities, including participation in the "Saturday Morning Science’ seminar series. Dr. Zhang will continue his collaboration with school teachers to conduct fly genetic science projects with school students. Finally, Dr. Zhang has supervised two middle school students on science projects and one of the projects competed at the state level. Due to his consistent outreach efforts Dr. Zhang has been invited to participate in NSF's 2013 STEM Science and Engineering Career Fair. By offering opportunities of hands-on research to students and reaching out to the local society, Dr. Zhang has inspired a life-long interest and passion for sciences in his students and trainees and brought science closer to the general public.
