The Schmidt lab invents and applies protein engineering technologies to study fundamental neuronal signaling processes at a cellular level. We are seeking mechanistic explanations for how neurons sense, integrate and exchange information, how pathologic changes in these processes relate to health and disease, and provide insights into new therapies for neuropsychiatric disorders including brain cancers.
Typical questions we ask are: What are the minimally required functional features of cellular components that regulate neuronal homeostasis and signal transduction? How does their activity change during normal development? What are specific activity patterns associated with disease onset? How can we re-engineer cellular signaling systems for therapeutic purposes? We answer these questions by inventing custom-made methods to observe, delineate and precisely control neuronal physiology. Our approach employs techniques from multiple disciplines including optogenetics, electrophysiology, and rational protein design.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Schmidt D. & Cho, Y.K. (2014) Natural photoreceptors and their application to synthetic biology. Trends in Biotechnology, doi:10.1016/j.tibtech.2014.10.007
Schmidt D., Tillberg P.W., Chen F., Boyden E.S. (2013) A fully genetically encoded protein architecture for optical control of peptide ligand concentration. Nature Communications 4:3019, doi:10.1038/ncomms4019
Schmidt D., del Marmol J., Mackinnon R. (2012) Mechanistic basis for low threshold mechanosensitivity in voltage-dependent K+ channels. PNAS 109(26):10352-7
Zamft, B.M., Marblestone, A.H., Kording, K., Schmidt, D., Martin-Alarcon, D., Tyo, K., Boyden, E.S., and Church, G. Measuring cation dependent DNA polymerase fidelity landscapes by deep sequencing. (2012) PLoS ONE 7, e43876.
Aimon S., Manzi J., Schmidt D., Poveda Larrosa J.A., Bassereau P., Tombes G.E.S. (2011) Functional Reconstitution of a Voltage-Gated Potassium Channel in Giant Unilamellar Vesicles. PLoS ONE 6(10): e25529.
Schmidt D., Cross S.R., Mackinnon R. (2009) A Gating Model for the Archaeal Voltage-Dependent K+ Channel KvAP in DPhPC and POPE:POPG decane lipid bilayers. J Mol Biol 390(5):902-12
Schmidt D., Mackinnon R (2008). Voltage-dependent K+ channel gating and voltage sensor toxin sensitivity depend on the mechanical state of the lipid membrane. PNAS 105(49):19275-80
Schmidt D.*, Jiang Q.X.*, Mackinnon R. (2006). Phospholipids and the origin of cationic gating charges in voltage sensors. Nature 444(7120):775-9