Curtis M. Loer, PhD - US grants

DESCRIPTION (Adapted from applicant's abstract): To function correctly in the nervous system, a neuron must produce an appropriate neurotransmitter. Little is known about the mechanisms that govern this choice within developing neurons. Since the same neurotransmitters are used by organisms throughout the animal kingdom, genes regulating neurotransmitter choice are likely to be conserved among simple and complex organisms. Therefore, it is proposed to study this problem in a simple organism which is readily amenable to genetic and molecular analysis, the nematode worm Caenorhabditis elegans. This study will examine the regulation of neurotransmitter-specific genes expressed in serotonergic neurons ('serotonergic marker genes') of C. elegans. C. elegans genes necessary for serotonin synthesis and packaging: tryptophan hydroxylase, dopa decarboxylase, and vesicular monoamine transporter have been identified. It is proposed to 1) identify regulatory elements by comparing promoters of the homologous marker genes from a closely-related species and performing promoter deletion analyses, 2) identify regulatory genes by screening for mutants that do not express or mis-express the serotonergic marker genes. The long term goal of these studies is to understand how genes control the expression of specific neuronal identities, in particular, the neurotransmitter type of a neuron. Such studies may allow us to understand better why neurological disorders target specific subsets of neurons and ultimately to develop therapies to control the expression of neurotransmitters in specific cells of the human nervous system.

Five research-productive faculty members from the biology and physics departments at the University of San Diego will purchase, install, maintain, and manage a shared laser scanning confocal microscope to advance research in the physiological, cellular, molecular, and biophysical sciences. Confocal microscopy is essential in providing sensitive, high resolution, three-dimensional, time-resolved imaging so as to characterize: ion transporter expression in aquatic animals (Patrick, Gonzalez), reactive oxygen species in plants (Baird), serotonergic neurons in worms (Loer), intracellular trafficking in cellular migration (Prigozhina) and the intramolecular dynamics of diffusing DNA molecules. Research by the PI and co-PIs is highly integrative and requires a breadth of confocal technology that will enable imaging and data acquisition over a wide range of magnification, ranging from individual macromolecules (DNA) and real-time imaging of events in live cells, to localizing molecules in whole mounts of tissues or intact organisms. The specifications of Olympus Fluo View 1000/IX81 inverted microscope will satisfy the confocal research and training requirements of the faculty and provide opportunities for new and collaborative projects.

The NSF award will be used to purchase a confocal microscope for five faculty members in the Biology and Physics departments at USD, three of which are women faculty, including one pre-tenure, junior faculty in Physics. USD is an undergraduate institution where 58% of students are women and 20% are underrepresented ethnicities. The PI and co-PIs have a strong record of productive, collaborative research with undergraduates throughout the year. Students from Mater Dei High School (80% Latino/a and 20% from economically disadvantaged backgrounds) and San Diego City College (57% women, 70% minority status) will also benefit from gaining skills in confocal technology in summer research with USD science faculty. Integration of confocal technology into our research-based curriculum will augment several biology and physics courses and provide an opportunity to develop an interdisciplinary microscopy techniques course for the new biophysics major. This state-of-the-art instrument will enrich the research and educational experience of students in STEM areas at USD and attract highly motivated undergraduates to science careers.