Gregory E. Demas - US grants

The Indiana University REU Site will provide a research program for undergraduates during summers of 2009-2013, though support provided by NSF Directorates of Biological Sciences (BIO) and Social, Behavioral and Economic Sciences (SBE). Ten students will be selected each year to participate in an intensive research program in an area of animal behavior. Students from biology, neuroscience, psychology and anthropology are welcome to apply. The goal is to increase students' likelihood to successfully enter a graduate school or a job in science. Students are matched with individual labs and have the opportunity to perform and complete their own research projects--including analyzing data, preparing findings in a poster format, and presenting at a concluding symposium. The program emphasizes an interdisciplinary environment beginning with introductory seminar meetings with a range of Animal Behavior faculty, and includes exposure to techniques of conducting genetic and neuroendocrine assays, collecting data in zoos, and making science accessible to the public. Students receive training in reasoning applied to the conduct of science with an emphasis on basic and applied animal behavior research, assistance in how to present research, strategies in taking GRE tests, and career options in science and education. Because the core emphasis is on the research experience, the scheduling of training events is designed to allow students to begin work in their host laboratories during the first week of the program. Students from institutions with limited research opportunities for research and those from groups under-represented in science are especially encouraged to apply. More information is available at http://www.indiana.edu/~animal/REU, or by contacting Linda Summers (812-855-9663 or cisab@indiana.edu) or the Program Director, Dr. Emilia Martins (812-855-1646 or emartins@indiana.edu).

This is an EAGER proposal to establish the foundation for subsequent research on the environmental, behavioral, and genetic determinants of reproductive hormone levels in indigenous arctic women. There is strong scientific evidence that concentrations of the steroid hormones investigated in this project influence the capacity to conceive and are significant risk factors for several diseases (e.g., breast and other cancers, cardiovascular disease), yet very little is known about the variation of these hormones among pre-menopausal women in the arctic. This EAGER project is an experimental project designed to evaluate whether genetic variation at specific loci contribute to hormonal variation in circumpolar ancestral (Central Asian) and descendant (indigenous South American) populations. The researchers expect this project to provide 1) validated field, laboratory and statistical approaches to hormone concentrations in women, and 2) valuable and novel data for the anticipated future study of circumpolar populations. In addition, the PI will be actively involved in community outreach in Alaska, Canada, and Greenland in order to inform indigenous communities of the findings from the EAGER research and solicit community interest and collaboration in a broader circumpolar study. This project is potentially transformative in both the scientific potential to define a specific genome related to steroid hormones and in the broader impacts of creating a community collaborative project that has the potential to gain deeper insight into fatal diseases affecting these communities.

Aggression is a widespread naturally-occurring behavior serving a range of adaptive functions including access to mates and resources. Testosterone produced by the gonads is frequently associated with high levels of aggression. However, in seasonal breeding animals aggression can be both intense and widespread during the non-breeding season when testosterone levels are undetectable. This means that aggression is regulated by more than one mechanism and there is little understanding of how non-breeding aggression is regulated. This research seeks to understand the physiological mechanisms that underlie seasonal variation of aggression using female Siberian hamsters as a model. This work is highly integrative and unlike most other studies that examine single factors it will consider many relevant endocrine parameters and their interactions to understand how the brain and hormones function to control seasonal aggression in females. These studies will provide important insights into the physiological mechanisms mediating aggression, and social behavior more broadly. Additionally, this proposal will allow for the continued mentorship of undergraduates and high school students in research directly related to this work. Communication of these research findings will include public lectures and scientific conferences, and journal articles, as well as specialized regional symposia and organizations focused on the advancement of underrepresented minorities in the sciences.

The researchers' data so far show that melatonin, the hormonal signal encoding photoperiod, drives seasonal changes in aggression, and further that adrenal hormones, such as DHEA, rather than gonadal hormones, may indirectly regulate aggression via conversion to active androgens or estrogens during periods when animals are non-reproductive. To examine seasonal switching from a gonadal to adrenal source of hormone, the proposed research tests the hypotheses that DHEA mediates non-breeding season aggression and that melatonin regulates DHEA release and its conversion to active hormones, which can then act on neural receptors. Specific Aim 1 will link seasonal changes in aggression and seasonal melatonin cues to neural receptor profiles (androgen and estrogen receptors) as well as a converting enzyme (aromatase, the enzyme that converts T to estradiol), via immunocytochemistry. Specific Aim 2 will determine whether changes in DHEA levels predict aggression among individuals across seasons by challenging animals in different photoperiods with ACTH, and assessing DHEA release. Lastly, Specific Aim 3 will test the hypothesis that short-day increases in melatonin mediate seasonal changes in DHEA by isolating the adrenal gland from other organs responsible for DHEA release and by using an in vitro bioassay to address localized action of melatonin on this organ and its subsequent production of DHEA. Collectively, the proposed work takes a whole organism approach and examines direct hormonal action on multiple tissues to determine the mechanisms underlying seasonal aggression in female hamsters using multiple levels of analysis. To facilitate proper storage and access of data, manuscripts will be published in open-access format, when possible, and on the lab website. Presentations will be made at international and national conferences, as well as in local venues to lay audiences, including high schools. Following processing of samples for the primary project, samples will be archived, and made accessible for collaborations from interested parties. Lastly, the PI will work with Indiana University Information Technology Services to archive data on the Research Data Complex (RDC), a dedicated server for hosting databases.

Virtually all animals, including humans, play host to a wide range of microorganisms such as bacteria and fungi that function within cells, tissues, and organs. Many of these microorganisms reside within the gut. Recent evidence suggests that this 'gut microbiome' exerts a surprising and powerful influence on the normal brain and on behavior in both adults and the young. How the gut microbiome influences the brain and behavior, however, is essentially unknown. This research will test a novel mechanism by which the gut microbiome may contribute to the development of offspring sociality by focusing on the shared mother-offspring microbiome in dwarf hamsters. The goal of the proposed research is to test the idea that disruption of the maternal microbiome, via antibiotic administration, alters the diversity and composition of the mother's gut microbiome and consequently affects the development of normal social behavior and related physiological parameters in her offspring. This research will also test whether the restoration of the maternal gut microbiome returns social behaviors to normal. Lastly, these studies will examine the role of bi-parental (i.e., mother and father) behaviors in preventing the adverse effects of a disrupted maternal microbiome on offspring social behavior. Collectively, these studies will provide fundamental knowledge of the basic mechanisms by which the maternal microbiome influences the development of offspring sociality. An understanding of these mechanisms will provide important basic knowledge that may ultimately inform treatment and prevention of debilitating disorders characterized by deficits of social functioning. In addition to training graduate student researchers, undergraduates in Indiana University's Research Experience for Undergraduates program and a local middle school teacher and middle school class will take part in the research. The middle school students will participate in activities focused on soil and gut microbes at the local Marble Hill Farm.

The precise physiological mechanisms underlying microbiome effects on the brain and social behavior, however, remain unknown. This research employs an animal model to elucidate the impact of maternal microbiome status on the development of offspring sociality as well as the mechanisms underlying observed microbiome-brain-behavior relationships. Specifically, the experiments utilize animals that display either bi-parental (i.e., both maternal and paternal) care or uni-parental (i.e., exclusively maternal) care to tease apart their relative contributions to offspring development. The goal of the proposed research is to test the specific hypotheses that: 1) disruption of the maternal microbiome via antibiotic administration alters the diversity and composition of gut microbiota and consequently offspring sociality, stress responsivity, and cytokine profiles; 2) disruption of neuroendocrine and/or neuroimmune systems mediates, at least in part, the effects on social behaviors; 3) repletion of the gut microbiome via fecal transplants restores normal social behaviors; and 4) bi-parental care modulates these effects by providing additional contributions of paternal behavior to buffer offspring. The proposed studies will provide valuable insight on the basic mechanisms of microbiome influences on maternal-offspring behavioral interactions, the role of paternal behaviors in buffering the influences of maternal microbiome disruption on offspring behavior, as well as the development of social behaviors more broadly.