Scott Laughlin, Associate Professor
B.S. in Biochemistry and Philosophy, University of Michigan, Ann Arbor, 2002
Ph. D. in Chemistry, University of California, Berkeley, 2008
Postdoctoral research at the Helen Wills Neuroscience Institute, University of California, Berkeley, 2008-2013
Phone: (631) 632-2642
Our research uses chemistry to examine how the brain works. How does the brain sense the environment? How does it decode that sensory information and control behavior? All of the brain’s many functions rely on its neural circuits—a complex web of neurons connected to each other in such a way that they can perform the logical operations that allow us to think, respond to stimuli, etc. Precisely how neural circuits perform their calculations is a mystery whose solution has wide ranging implications for human health. Using organic synthesis, molecular biology, and behavioral neurobiology, we create chemical tools to help reveal the structure of neural circuits in living animals.
Neural synapse-crossing fluorophores
The neurons that make up a circuit are linked to each other and transmit information by synapses. In our research, we exploit this synaptic connection to visualize neural circuitry. We identify synthetic and naturally occurring molecules that are able to pass across the neural synapse, and we modify their structures, for example, by adding a fluorophore. Once applied to neurons at the beginning of a circuit, these synapse-crossing fluorescent molecules move throughout the brain, allowing us to take detailed pictures of neural circuitry.
Fluorescent indicators of neural activity
In response to a sensory stimulus, such as a smell, sound or sight, the neurons in a circuit burst with activity in order to process the information. At the same time, most other neurons in the brain, and in other neural circuits, are dormant. We exploit this short burst of activity to highlight the neural circuit responsible for processing a given sensation. In one strategy, we engineer small molecules and enzymes to permanently turn fluorescent in response to a burst of neural activity. By applying these tools to the brain and exposing the animal to an interesting smell, sound or sight, we make only those neurons responsible for processing the sensation fluorescent, allowing us to image the neural circuit at high resolution.
Small molecule control of behavior
The brain detects most sensory stimuli with a complex array of sensory neurons. However, some sensations can be reduced to a single, perfectly-defined molecule structure. In our research, we search for molecular structures that cause instinctive behaviors in small animal models like larval zebrafish. These behaviorally active molecules give us exquisite control over the neural circuits for behaviors like fear and anxiety, allowing us to dissect their neural circuits using the above chemical strategies and apply our findings to improving human health.
Dehnert, K.W., Baskin, J.M., Laughlin, S.T., Beahm, B.J., Naidu, N.N., Amacher, S.L.
& Bertozzi, C.R.
Imaging the sialome during zebrafish development with copper-free click chemistry. Chembiochem, 2012, 13, 353–7.
Dehnert, K.W., Beahm, B.J., Huynh, T.T., Baskin, J.M., Laughlin, S.T., Wang, W., Wu, P., Amacher, S.L. & Bertozzi, C.R. Metabolic labeling of fucosylated glycans in developing zebrafish. ACS Chem. Biol., 2011, 6, 547–52.
Baskin, J.M.*, Dehnert, K.W.*, Laughlin, S.T.*, Amacher, S.L. & Bertozzi, C.R. Visualizing enveloping layer glycans during zebrafish early embryogenesis. *These authors contributed equally to this work. Proc. Natl Acad. Sci. U.S.A., 2010, 107, 10360–5.
Laughlin, S.T. & Bertozzi, C.R. In vivo imaging of Caenorhabditis elegans glycans. ACS Chem. Biol., 2009, 4, 1068–72.
Laughlin, S.T. & Bertozzi, C.R. Imaging the glycome. Proc. Natl Acad. Sci. U.S.A., 2009, 106, 12–7.
Czlapinski, J.L., Schelle, M.W., Miller, L.W., Laughlin, S.T., Kohler, J. J., Cornish,
V. & Bertozzi, C. R.
Conditional glycosylation in eukaryotic cells using a biocompatible chemical inducer of dimerization.
J. Am. Chem. Soc., 2008, 130, 13186–7.
Laughlin, S.T., Baskin, J.M., Amacher, S.L. & Bertozzi, C.R. In vivo imaging of membrane‐associated glycans in developing zebrafish. Science, 2008, 320, 664–7.
Laughlin, S.T. & Bertozzi, C.R. Metabolic labeling of glycans with azido sugars for visualization and glycoproteomics. Nat. Protoc., 2007, 11, 2930–44.
Baskin, J.M., Prescher, J.A., Laughlin, S.T., Agard, N.J., Chang, P.V., Miller, I.A.
& Bertozzi, C.R.
Copper‐free click chemistry for covalent labeling in living systems. Proc. Natl Acad. Sci. U.S.A., 2007, 104, 16793–97.
Rabuka, D.R., Hubbard, S.C., Laughlin, S.T., Argade, S.P. & Bertozzi, C.R. A chemical reporter strategy to probe glycoprotein fucosylation. J. Am. Chem. Soc., 2006, 128, 12078–79.
Laughlin, S.T., Agard, N.J., Baskin, J.M., Carrico, I.S., Chang, P.V., Ganjuli, A.S.,
Lo, A., Prescher, J.A. & Bertozzi, C.R. Metabolic labeling of glycans with azido sugars for visualization and glycoproteomics. Meth. Enzymol., 2006, 415, 230–250.
de Graffenried, C.L., Laughlin, S.T., Kohler, J.J. & Bertozzi, C.R. A small‐molecule switch for Golgi sulfotransferases. Proc. Natl Acad. Sci. U.S.A., 2004, 101, 16715–20.
Kohler, J.J., Czlapinski, J.L., Laughlin, S.T., Schelle, M.W., de Graffenried, C.L.
& Bertozzi, C.R.
Directing flux in glycan biosynthetic pathways with a small molecule switch. Chembiochem, 2004, 5, 1455–8.