Our laboratory is currently involved in three areas of basic neurobiological research. One area comprises studies of molecular pathways underlying the regulation of neuronal growth cone dynamics and interactions leading to neuronal arbor formation. In particular, we have focused on the mechanisms which receptors and signaling factors use to mediate self- and homologue-avoidance in the process of defining cell arbor boundaries, a phenomenon that is known as tiling and defines the topology of sensory and motor fields. Our model system is the medicinal leech nervous system, for which we have developed or adapted all the tools required for modulating the expression of specific genes in individual embryonic or adult neurons.
Figure 1. Bilateral Pair of Central Neurons in the Medicinal Leech
A second area consists of studies of the roles of gap junctions in the early differentiation of the central nervous system. We have cloned over one dozen leech innexins, several of which are expressed in nervous tissue. In one set of studies, we showed that innexins can not only form gap junctions but can also form functional hemi-channels that can be used in intercellular signaling via small molecules such as ATP - we are currently testing this signaling pathway in gangliogenesis. In another set of studies, we are assaying the role of innexins in interactions between segmental homologs that result in the retraction of some neuronal projections and the maintenance of others.
Figure 2. MALDI Imaging of Peptide Distributions in Leech Embryo Whole Mounts
The third area of current research consists of an international collaboration with several laboratories (in other UCSD departments as well as with colleagues in Lille, FRANCE) on the novel application of Imaging Mass Spectrometry (MALDI Imaging) to the mapping of peptides and proteins in leech embryos and adult nervous system sections. In order to study at a systems level the expression profiles, we are developing tools for molecular imaging using scanning MALDI-TOF MS/MS to obtain spectra in a raster analysis of whole-mount embryos and serially-sectioned adult ganglia, as well as software tools for the analysis of the enormous amount of data thus obtained. In particular, we are comparing gene expression in developing, regenerating and neuro-immune compromised nervous systems in order to analyze how the nervous system responds to various kinds of insults.
Figure 3. Pair of Live Medicinal Leech Embryos
Finally, we are also involved in a multidisciplinary project at the boundary of Neuroscience and Architecture. This project brings together human brain activity monitoring using portable high-definition EEG with cutting-edge Virtual Reality facilities on campus to assay human responses to the built environment, in particular, as the subjects attempt to navigate through a complex building. This project has exciting practical ramifications, for example, in providing evidence for the design of better healthcare and educational facilities, as well as testing therapies for improving the status of humans with neural impairment conditions.
Innexins Form Two Types of Channels. L. Bao, S. Samuels, S. Locovei, E. R. Macagno, K. J. Muller, and G. Dahl. FEBS Letters 581:5703-5708 (2007).
Microbial challenge promotes the regenerative process of the injured central nervous system of the medicinal leech by inducing the synthesis of antimicrobial peptides in neurons and microglia. D. Schikorski, V. Cuvillier Hot, M. Leippe, C. Wichlacz-Boidin, C. Slomianny, E. Macagno, M. Salzet and A. Tasiemski. J. Immunol. 181:1083-1095 (2008).
The Receptor Phosphatase HmLAR2 Sheds its Ectodomain and Collaborates with Focal Adhesion Proteins in Filopodial Tips to Control Growth Cone Morphology. M.W. Baker, S.M. Peterson and E.R. Macagno. Dev. Biol. 320:215-225 (2008).
Construction of a Medicinal Leech Transcriptome Database and Its Application to the Identification of Leech Homologs of Neural and Innate Immune Genes. E. R. Macagno, T. Gaasterland, L. Edsall, V. Bafna, M. B. Soares, T. Scheetz, T. Casavant, C. Da Silva, P. Wincker, A. Tasiemski and M. Salzet. BMC Genomics 11:407 (pp. 1-13) (2010).
Expression Levels of a LAR-like Receptor Protein Tyrosine Phosphatase Correlate with Neuronal Branching and Arbor Density in the Medicinal Leech. M. W. Baker and E. R. Macagno. Dev. Biol. 344:346-357 (2010).
The receptor protein tyrosine phosphatase HmLAR1 is up-regulated in the CNS of the adult medicinal leech following injury and is required for neuronal sprouting and regeneration. J. Sethi, B. Zhao, V. Cuvillier-Hot, C. Boidin-Wichlacz, M. Salzet, E. R. Macagno and M. W. Baker. Mol. Cell. Neurosci. 45:430-438 (2010).
Wireless Physiological Monitoring and Ocular Tracking: 3D Calibration in a Fully-Immersive Virtual Health Care Environment. L. Zhang, Y. Chi, E. Edelstein, J. Schulze, K. Gramann, A. Velasquez, G. Cauwenberghs and E. Macagno. Conf. Proc. IEEE Eng. Med Biol. Soc. 2010:4464-4467 (2010).
Automated Querying and Identification of Novel Peptides Using MALDI Mass Spectrometric Imaging. J. Bruand, S. Sistla, P. Dorrestein, M. Ghassemian, C. Meriaux, M. Wisztorski, I. Fournier, M. Salzet, T. Gaasterland, E. Macagno and V. Bafna. J. Proteome Res. 10:1915-1928 (2011).
Multiple Changes in Peptide and Lipid Expression Associated with Regeneration in the Nervous System of the Medicinal Leech. Meriaux C, Arafah K, Tasiemski A, Wisztorski M, Bruand J, Wichlacz-Boidin C, Desmons A, Debois, D, Laprévote O, Brunelle A, Gaasterland T, Macagno ER, Fournier I, Salzet M. PLoS ONE, in press (2011).
Form Follows Function: Bridging Neuroscience and Architecture. E.A. Edelstein and E. Macagno. In: Sustainable Environmental Design in Architecture: Impacts on Health, S Rassia, Editor, Springer, in press (2011).
Eduardo Macagno received his Ph.D. from Columbia University in 1968. He was on the faculty of Columbia from 1973 to 2000. From 1993 to 2000 he served as Associate Vice President for Research and Graduate Education and Dean of the Graduate School of Arts and Sciences at Columbia. He joined the faculty of the Division of Biological Sciences as Founding Dean in 2001. He is the Editor of Developmental Neurobiology and the President of the Academy of Neuroscience for Architecture. He also serves on review committees for the Life Sciences Research Foundation and the W. M. Keck Foundation.