We are pleased to announce that the winner of the 2017 JCS Prize is Seth Zimmerman for his paper entitled ‘Cells lay their own tracks – optogenetic Cdc42 activation stimulates fibronectin deposition supporting directed migration’ (Zimmerman et al., 2017).

The prize, $1000, is awarded annually to the first author of the paper that is judged by the Editors and Editorial Board to be the best eligible paper published in the Journal of Cell Science that year. To be considered for the prize, the first author must be a student or a postdoc of no more than five years standing.

Seth grew up in Binghamton, New York and received his undergraduate degree in biology from Rochester Institute of Technology (RIT). At RIT, he participated in the undergraduate research program under the direction of Dr Irene Evans studying the effects of prions on yeast transcription using microarray technology.

Upon graduating, Seth was undecided about whether to pursue a career in research. However, in 2009, he accepted a post-baccalaureate research fellow position at the National Institutes of Health which fostered his fascination with the molecular basis of disease. Under the guidance of Dr Sharon Milgram, he used proteomic approaches to identify ZO-2, a cell–cell junction protein, as a retromer complex protein sorting nexin-27 (SNX27) binding partner. Using biochemical approaches and confocal microscopy, Seth confirmed the specific interaction and found that it was important to maintain epithelial barrier function (Zimmerman, 2013).

His experience at the NIH solidified Seth's love of the scientific process. In 2011, he began his PhD at the University of North Carolina at Chapel Hill under the direction of both Dr James Bear and Dr Brian Kuhlman. Under Dr Kuhlman's guidance and expertise in computational protein design, Seth collaborated with other lab members to engineer a suite of optogenetic dimers called iLID that reversibly dimerize in the presence of blue light. Through computationally guided mutagenesis they produced a range of dimers that function over a wide range of affinities while maintaining a broad dynamic range (Guntas, 2015; Zimmerman, 2016)

Seth then applied iLID to studying the role of Rho GTPase in cell migration. With overlapping signaling pathways, crosstalk between family members and similar downstream effects on the actin cytoskeleton, the role of these GTPases in cell migration is far from clear. Under the guidance of Dr Bear, Seth saw an opportunity to assay the individual contributions of Rac and Cdc42, using the iLID technology developed in the Kuhlman lab. By fusing guanine nucleotide exchange factors (GEFs) – activators of small GTPases – specific for either Rac or Cdc42 to one subunit of iLID and by anchoring the other subunit to the plasma membrane, he was able to reversibly target the two GTPases for activation. Furthermore, this technique provided him with subcellular spatial and temporal control of the GTPases. By using this tool, Seth pioneered techniques to guide cells up a gradient of light and determine how each GTPase contributed to directed cell migration. Specifically, he found that Cdc42 induced local secretion of the extracellular matrix protein fibronectin, which enhanced the cells directed migration. With this in mind, Seth proposed a model in which local Cdc42 activity at the front of a migrating cell not only produces the cytoskeletal forces necessary for migration but also induces secretion of fibronectin that acts as a track for the cell to migrate on, and reinforces the polarized signaling (Zimmerman, 2017).

In June 2017, Seth started a postdoc position at Duke University in Dr Chris Counter's Lab, where he is studying the role of Ras in cancer progression by screening for genetic vulnerabilities.

References

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