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DR. EVA MARY KAVAN PRIZE FOR EXCELLENCE IN RESEARCH ON THE BRAIN

The Eva Mary Kavan Prize for Excellence in Research on the Brain was established in 1999 by a generous endowment from Dr. Eva Kavan. Dr. Kavan earned her doctorate degree in medicine at Charles University in her native Prague, Czechoslovakia. She came to UCLA in 1956 at a time when there were only five hospitals performing open-heart surgery with a heart-lung machine; UCLA had one of the first teams to do open-heart surgery in the West. Dr. Kavan was a pioneer in the administration of anesthesia, utilizing the electroencephalogram to perform important research on the effects of the heart-lung machine on brain function during open-heart operations. Dr. Kavan has created this award, which is to be announced at the H.W. Magoun Lecture, to encourage a talented young scholar to pursue scientific research on the brain.
Each year a prize is given to one graduate student who has demonstrated excellence in his or her field of basic research in neuroscience. The awardee is selected by a faculty committee, which evaluates nominations solicited from the UCLA neuroscience community. One student from any neuroscience research department at UCLA receives a cash prize and a certificate of merit.

This year, Sangmok Kim was chosen as the recipient of the 15th Eva Mary Kavan Prize for Excellence in Research on the Brain. Sangmok is a senior graduate student in the Interdepartmental Program for Neuroscience. In the laboratory of Dr. Kelsey Martin he has completed a very elegant piece of work, which is being revised for Cell, with Sangmok as the first of only two authors. Sangmok received a BS and MS in biochemistry from Kangwon University in Korea, spent two years as a research assistant in David Linden’s lab at John Hopkins University, and then joined the NSIDP graduate program at UCLA in 2006. With specific interests in the cell biology of learning-related neuronal plasticity, he completed rotations in the Martin and O’Dell laboratories, where it became clear that Sangmok was a particularly gifted experimentalist.

In his PhD research, Sangmok has focused on the question of how gene expression is spatially regulated within neurons during synapse formation and synaptic plasticity. He has addressed these questions in the Aplysia californica sensory-motor neuron culture system, where he can monitor synapse formation and plasticity at the level of individual neurons. In the first part of his thesis research, Sangmok collaborated with postdoctoral fellow Ohtan Wang and graduate student Elliott Meer to develop methods to study the mechanisms underlying mRNA localization to synapses and to visualize local translation during synaptic plasticity. This work was based on previous studies from the Martin lab showing that mRNAs localized to distal sensory neurites where their translation was critical to synapse-specific forms of neuronal plasticity. The Martin lab previously reported the identification of a large population of localized mRNAs (Moccia et al 2003), and discovered that one of the mRNAs that localized to sensory neurites, encoding the sensorin neuropeptide, underwent regulated localization upon synapse formation. Specifically, the lab found that sensorin mRNA localized diffusely to neurites in synaptically unconnected neurons, but concentrated at synapses following pairing with motor neurons. Together with Dr. Wang and Elliott Meer, Sangmok developed a series of sensorin reporter mRNAs to dissect the mechanisms underlying its synaptic localization and to directly monitor sensorin translation during long-term facilitation of sensory-motor synapses. They discovered that the 3’UTR of sensorin mediates its transport from soma into the neurite, while the 5’UTR is required for concentration of the mRNA at synapses. Using mutatgenesis and structural analysis by chemical probing, they were able to identify a 66 nucleotide-long stemloop structure that is both necessary and sufficient for synaptic mRNA localization. These findings were published in a PNAS article in March 2012, with Sangmok as second author (Wang and Meer were co-first authors). Sangmok and Ohtan used a reporter containing the 5’ and 3’ UTR of sensorin fused to the photoconvertible fluorescent protein dendra2 to visualize local translation during plasticity. By expressing the reporter in sensory neurons, and photoconverting from green to red, they were able to monitor translation in real-time by imaging the appearance of newly translated green signal. These studies showed that localized stimulus led to spatially restricted translation that was synapse and stimulus-specific. Moreover, they discovered that stimulus-induced translation only occurred at the synapse, and required a calcium-dependent retrograde signal from the motor neuron. The results of these studies were published as a full-length article in Science in June 2009, with Sangmok as second author.

In his more recent work, Sangmok has addressed the fundamental question of whether the spatial regulation of gene expression is mediated primarily by RNA localization or by regulated translation. He uses a beautiful culture system in which a single bifurcated neuron is plated with a target motor neuron, with which it forms a glutamatergic synapse, and a nontarget motor neuron, with which it fasciculates but does not form a chemical synapse. This system allowed him to determine whether and how synaptogenic signals regulate the transport of RNAs out of the soma and how they regulate translation. Sangmok showed that rRNA, RNA binding proteins and mRNAs are transported equally well to both branches. However, he found that protein synthesis was very significantly enriched in branches contacting synaptic contacts. These results indicate that the spatial regulation of gene expression during synapse formation is mediated at the level of translation, rather than at the level of RNA targeting. He went on to show that this translational regulation requires the calcium-dependent release of netrin-1 from the postsynaptic motor neuron, with binding to the netrin-1 receptor DCC on the sensory neuron. A manuscript describing these results is under revision for Cell, with Sangmok as the first author. Sangmok’s work is beautiful, technically challenging and elegant, and the finding is important for understanding how gene expression is regulated during wiring of the nervous system. He is currently extending this approach to determine whether this principle of generalized RNA localization but localized translational regulation extends to synaptic plasticity. Finally, Sangmok is a fantastic molecular biologist, electrophysiologist and cell biologist, and does not shy away from technical challenges. He is a dedicated, creative and highly effective neuroscientist who has made major contributions during his graduate training, and very deserving of the Kavan Prize.

Previous Eva Kavan Prize Recipients
Year Student Mentor and Research Project
1999 1st Eva Kavan Prize Recipient Albert Cha Francisco Bezanilla Laboratory
Research Project: Ion channels
2000 2nd Eva Kavan Prize Recipient U. Valentin Nägerl Istvan Mody Laboratory
Research Project: Calbindin and other intracellular calcium-binding proteins in the calcium-buffering capacity of central neurons and the role of these proteins in temporal lobe epilepsy
2001 3rd Eva Kavan Prize Recipient Michael Zeineh Susan Bookheimer Laboratory
Research Project: Novel methods of increasing the resolution of functional magnetic resonance imaging
2002 4th Eva Kavan Prize Recipient Christine Bredfelt Dario Ringach Laboratory
Research Project: Focused on one of the basic transformations in visual processing observed between the lateral geniculate nucleus and primary visual cortex (area V1)
2003 5th Eva Kavan Prize Recipient Jeffrey Gotts Marie-Françoise Chesselet Laboratory
Research Project: The mechanism by which cortical lesions induce a large increase in cell numbers in the subependymal layer of adult rats
2004 6th Eva Kavan Prize Recipient Alison Burggren Susan Bookheimer Laboratory
Research Project: Alzheimer’s Disease
2005 7th Eva Kavan Prize Recipient Kim Thompson Kelsey Martin Laboratory
Research Project: Pioneering studies on the mechanisms whereby signals are retrogradely transported from distal synapses to the nucleus in neurons
2006 8th Eva Kavan Prize Recipient Mary Kay Lobo X. William Yang Laboratory
Research Project: Application of molecular genetic tools to study basal ganglia biology and disease
2007 9th Eva Kavan Prize Recipient Joshua Johansen H. Tad Blair Laboratory
Research Project: Groundbreaking work on the circuit and computational mechanisms of teaching signal processing in the fear conditioning system
2008 10th Eva Kavan Prize Recipient Michael Oldham Daniel Geschwind Laboratory
Research Project: Foundational research on the organization of the human brain transcriptome
2009 11th Eva Kavan Prize Recipient Tiago Carvalho Dean Buonomano Laboratory
Research Project: How excitatory and inhibitory synaptic plasticity interact in a concerted manner to govern neuron behavior
2010 12th Eva Kavan Prize Recipient Kate Wassum Nigel Maidment Laboratory
Research Project: Identifying dissociable roles for endogenous opioids in mediating reward palatability and incentive learning.
2011 13th Eva Kavan Prize Recipient Erin Gray Tom O'Dell Laboratory
Research Project: Electrophysiological and molecular studies of the role of AMPA receptor phosphorylation in synaptic plasticity.
2012 14th Eva Kavan Prize Recipient Austin Hilliard Stephanie White Laboratory
Research Project: Human cognitive abilities that are articulated in the domains of music and language; neuromolecular networks involved in how the brain accomplishes vocal learning, such as speech, using the songbird as a model system.
2013 15th Eva Kavan Prize Recipient Sangmok Kim Kelsey Martin Laboratory Research Project: How gene expression is spatially regulated within neurons during synapse formation and synaptic plasticity; addressing these questions in the Aplysia californica sensory-motor neuron culture system, in order to monitor synapse formation and plasticity at the level of individual neurons.



 

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