ACL: Advent of Complex Life - MIT Astrobiology Team

Nicole King
University of California, Berkeley
Department of Molecular and Cell Biology
Department of Integrative Biology
E-mail: nking at berkeley dot edu

Nicole King is an Assistant Professor of Genetics and Development in the departments of Molecular and Cell Biology and Integrative Biology at the University of California at Berkeley. Her studies focus on choanoflagellates and the evolution of multicellular animals from their unicellular ancestors. Dr. King holds a B.S. in Biology from Indiana University (1992), a Ph.D. in Biochemistry from Harvard University (1999), and was a post-doctoral fellow at the University of Wisconsin (2000-2003). Dr. King was named a Pew Biomedical Scholar in 2004, received the George A. Bartholomew Award in Comparative Physiology from the Society for Integrative and Comparative Biology in 2004, and was named a MacArthur Fellow in 2005.

Nicole King Laboratory Web site

The King lab is interested in the origin of specialized sensory structures in complex organisms.  Our NASA/NAI work will focus on the transition from motile flagella to sensory cilia during the transition to metazoan multicellularity. For many years vertebrate primary cilia were considered little more than the cellular equivalent of vestigial organs, relics of animal evolution from their unicellular flagellate ancestors.  However, recent studies have revealed important environmental perception functions for this often overlooked structure in development and evolution (1).  Modified primary cilia function as photoreceptors in the eye, odorant receptors localize to cilia in the nose, and mechanosensors on cilia in the kidney respond to fluid flow (2).  Primary cilia are needed for embryonic development, including left-right axis determination (3), and have been linked to activity of the hedgehog signaling pathway in neurons (4) and initiation of calcium influx in the kidney epithelium (5).  Mutations in protein components of either process can lead to aberrant cell proliferation and carcinogenesis (6,7).  These newly described roles for cilia in vertebrates underscore their importance as cellular sensors and raise questions of when and how they evolved during the transition to metazoan multicellularity

The King lab will investigate the origin of primary cilium function by studying the apical flagellum of the unicellular choanoflagellate Monosiga brevicollis, which uses this structure for propulsion and as a cellular sensor, having both a motile flagellum and components of ciliary signaling pathways.  Choanoflagellates represent the closest single-celled relative of animals (8).  This will provide a simple system in which to study the ancestral function of primary cilia in single-celled organisms and yield insight into how these roles evolved during the transition to multicellularity of complex organisms.

REFERENCES

1. Salisbury, J.L. (2004). Primary cilia: putting sensors together. Curr. Biol. 14, R765-R767.
2. Singla, V. and Reiter, J.F. The primary cilium as the cell’s antenna: signaling at a sensory organelle. Science 313 629-633.
3. Nonaka, S. et al. (1998). Randomization of left-right asymmetry due to loss of nodal cilia generating leftward flow of extraembryonic fluid in mice lacking KIF3B motor protein. Cell 95, 829-837.
4. Caspary, T., Larkins, C.E., and Anderson, K.V. (2007). The graded response to Sonic Hedgehog depends on cilia architecture. Dev. Cell 12, 767-778.
5. Praetorius, H.A. and Spring, K.R. (2001). Bending the MDCK cell primary cilium increases intracellular calcium. J. Membr. Biol. 184, 71-79.
6. Wang, Y., McMahon, A. P., and Allen, B. L. (2007). Shifting paradigms in Hedgehog signaling. Curr. Opin. Cell Biol. 19, 159-165.
7. Pazour, G. J. and Witman, G. B. (2003). The vertebrate primary cilium is a sensory organelle. Curr. Opin. Cell Biol. 15, 105-110.
8. King, N. The unicellular ancestry of animal development. (2004). Dev. Cell 7 313-325.