Rodney K. Murphey - US grants

DESCRIPTION: The long term goal of the proposal is to understand how the specific patterns of synaptic connectivity between neurons are established. The orderliness of this process is crucial as mistakes in connectivity can disrupt neural circuits, and block proper function of the nervous system in all organisms including man. How neurons select their synaptic partners at a molecular level remains largely unsolved. The applicant and his colleagues will apply molecular, genetic, and electrophysiological methods to directly assay genes that function in the process of establishing synaptic connections. In this project, they will focus on the sensory nervous system of adult Drosophila. They have characterized a set of enhancer trap insertion lines that are expressed in specific subsets of sensory axons. Mutations caused by the insertion or excision of the P element will be characterized to determine the nature of the defects they cause in neuronal differentiation. Characterization of the genes identified by these insertions may aid in the understanding of the molecular processes that establish specific patterns of synaptic connections. Cloning and sequencing of the relevant genes will provide a description of their products. Finally, anatomical and electrophysiological assays for the function of the genes will be developed. Since many of the genes will be common to humans and flies, the identification of these genes may prove to be of clinical relevance.

This award provides funds to the Neuroscience and Behavior Program at the University of Massachusetts to establish a Research Experiences for Undergraduates Site. This program will take advantage of a unique neuroscience community that exists in this regional site. Neuroscientists at each of five colleges in the Amherst area are members of the University of Massachusetts Neuroscience and Behavior Program (NSB). This program will bring undergraduates into a laboratory environment where they will become members of a research team. This approach will facilitate the development of mentor-protege relationships, which may have a profound and long-lasting affect on career choices. The Program will consist of an eight-week research project in one of the laboratories. The laboratory work is designed to introduce students to one of the three specialty areas in neuroscience represented in the NSB Program; Learning and Behavior Neuroendocrinology, and Neurodevelopment. In addition to their laboratory work, students will attend a series of weekly workshops designed to provide an overview of neuroscience by introducing the knowledge and technology of laboratories outside the one in which the student works. In this way REU students will become familiar with a broad segment of neuroscience and thus be better prepared to choose careers in the neurosciences. The REU program will be followed up by encouraging work in the home institutions. Qualified undergraduates will be recruited from the five local institutions as well as from the national undergraduate population. The program will focus special attention on recruiting groups that are under-represented in science - women and minorities. In addition, personal contacts with faculty at a number of institutions with large minority populations have agreed to help identify qualified minority undergraduates for the program. Since the REU faculty is made up of 28% women and minorities, appropriate role models and mentors will be available for all participants.

The brain depends for its normal function on the specialized functional connections called synapses between nerve cells. These highly specialized structures have a great variety of sizes and ultrastructural features of their membranes, and can utilize a variety of molecules as neurotransmitters to carry information from one cell to another. This project uses as a model system a particular giant synapse in a visual-motor pathway, between a giant fiber and a motor neuron that is found in the central nervous system of the fruitfly, Drosophila; this organism also has a very well understood genetic background. Physiological, anatomical, and molecular tools, along with mutations and transgenic approaches, will be used to examine the molecular basis for the assembly of this giant synapse during development. The particular interest is in a molecular signal within the giant fiber that is carried back up the fiber to the cell nucleus, to regulate the formation of synaptic specializations.
Results will be important for developmental biology as well as neuroscience, and the project will also train undergraduate and graduate students in neuroscience.

DESCRIPTION (provided by applicant): The overall goal of this application is to understand the transformation of a motile growth cone into a sedentary synapse. We will use the Drosophila giant fiber (GF) system as a model to study the way in which a single axon recognizes the target area and makes a synapse with appropriate partners. Through targeted gene expression in the GF and its synaptic partners, we will explore the molecular aspects of this dynamic transformation. Our hypothesis is that semaphorin1a, which is well known for its role as a ligand during pathfinding, has a second role as a receptor during synaptogenesis and that it is critical to the delicate and dynamic molecular interactions that control the transition from growth cone to synapse. In order to better understand this new role for semaphorin1a, we will dissect the intracellular domain of semaphorin1a and determine its function during synapse formation. We will also examine putative downstream signals and will focus on enabled as a potential partner for semaphorin1a in stopping the growth cone. Finally, we will assay the dynamic regulation of proteins like semaphorin1a by the ubiquitin cascade. One of the first mutants isolated in the Drosophila giant fiber system was bendless, a defect in an E2 component of the ubiquitin cascade that causes a defect in the maturation of the giant synapse. We propose to revisit these early findings to assess the targets for the ubiquitin cascade and how they contribute to the dynamic processes that underlie the transition from growth cone to synapse.

URM:?Integrative Biology For Future Researchers?

NSF funding will establish an Undergraduate Research and Mentoring Program in the Department of Biological Sciences at Florida Atlantic University (FAU). The objectives of the URM program are to attract, mentor, and prepare undergraduate students historically underrepresented in scientific research for graduate studies in life sciences. FAU is a minority institution as well as a Hispanic serving university. The undergraduate scholars will participate in weekly meetings with the PIs (academic mentoring) to discuss their projects and receive feedback on their research experience and in activities aimed at strengthening their science related skills. Each student will also be paired with a faculty mentor (research mentoring) who will train and guide the student in the specific area of research of the mentor. The areas of research include; a) Conservation Biology, b) Marine Biology and Behavior, and c) Molecular, Cellular and Developmental Biology. These areas will be linked together by judicious choice of projects that will highlight the integrated nature of the program. The FAU-URM program will train students in a variety of research areas that will facilitate their movement into, graduate programs In addition; this URM will enhance the workforce development for SE Florida in anticipation of growing employment opportunities in life science institutions. For example, Scripps of Florida, the Torrey Pines Institute the USGS are adding facilities on or adjacent to FAU campuses as well as a variety of nearby state and federal laboratories. PIs: Rodney Murphey, Florida Atlantic University, Chair of the Department of Biological Sciences rmurphey@fau.edu ; Evelyn Frazier, Florida Atlantic University, Department of Biological Sciences, efrazier@fau.edu. For additional information, visit http://www.science.fau.edu/biology/

Abstract The central goal of this proposed program is to expand the pool of students from Florida Atlantic University (FAU) who enter PhD, MD/PhD, or related programs in biomedical science. FAU services students in Florida's fast growing Broward and Palm Beach County, and represents the most diverse four-year public university in Florida. The institution has recently expanded the number of research laboratories and is forming partnerships with Scripps Florida and Max Planck Florida, dramatically enhancing the research opportunities for undergraduates. This proposal leverages these opportunities by identifying promising underrepresented students from over 5000 majors in Biology, Psychology, and Neuroscience programs that may be interested in research careers, and engaging them in a critical thinking and research-intensive curriculum beginning sophomore year. We have developed three years of curriculum that includes specialized courses in critical thinking, research approaches, and scientific communication. Students will participate in laboratory research at FAU, Scripps, or Max Planck. As rising juniors, they will attend a summer internship at a partner Research Intensive Institution. Students will be paired with an Academic Mentor, a Research Mentor and a Near-Peer Mentor (graduate student) to provide support. One-on-one mentorship will be complemented by a diverse set of workshops throughout the three-year program. Recruitment to this program will leverage existing support networks for Freshman and other underrepresented groups, as well as a commitment by FAU to establish a Pre-URISE program that exposes students to research opportunities early in their freshman year. The completion of this program will provide support for underrepresented students to engage in research and receive mentoring that will promote matriculation to PhD, MD/PhD, or similar programs.