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.)
- Nedrud D, Coyote-Maestas W, Schmidt D. A large-scale survey of pairwise epistasis reveals a mechanism for evolutionary expansion and specialization of PDZ domains. Proteins. 2021 Feb 23. doi: 10.1002/prot.26067.
- Pronk NP, McLellan DL, Dennerlein JT, Anderson P, Karapanos M, Nagler E, Schmidt D, Spoonheim J, Wallace LM, Sorensen G. Building vapacity for integrated occupational safety, health, and well-being initiatives using guidelines for total worker health® approaches. J Occup Environ Med. 2021 May 1;63(5):411-421.
- Coyote-Maestas W, Nedrud D, Okorafor S, He Y, Schmidt D. Targeted insertional mutagenesis libraries for deep domain insertion profiling. Nucleic Acids Res. 2020 Jan 24;48(2):1010.
- Coyote-Maestas W, He Y, Myers CL, Schmidt D. Domain insertion permissibility-guided engineering of allostery in ion channels. Nat Commun. 2019 Jan 17;10(1):290
- Geurts YM, Dugué PA, Joo JE, Makalic E, Jung CH, Guan W, Nguyen S, Grove ML, Wong EM, Hodge AM, Bassett JK, FitzGerald LM, Tsimiklis H, Baglietto L, Severi G, Schmidt DF, Buchanan DD, MacInnis RJ, Hopper JL, Pankow JS, Demerath EW, Southey MC, Giles GG, English DR, Milne RL. Novel associations between blood DNA methylation and body mass index in middle-aged and older adults. Int J Obes (Lond). 2017 Oct 16.
- Schmidt D, Cho, YK. Natural photoreceptors and their application to synthetic biology. Trends Biotechnol. 2015;33(2):80-91.
- Schmidt D, Tillberg PW, Chen F, Boyden ES. A fully genetically encoded protein architecture for optical control of peptide ligand concentration. Nat Commun. 2014;5:3019.
- Schmidt D, del Marmol J, Mackinnon R. Mechanistic basis for low threshold mechanosensitivity in voltage-dependent K+ channels. Proc Natl Acad Sci U S A. 2012;109(26):10352-10237.