Our goal is to develop and deploy optogenetic approaches that mimic molecular and mechanical stimuli that a cell encounters at the subcellular level and direct important cell behaviors such as migration, cell division and differentiation. By controlling cellular behaviors with light and simultaneously measuring the cellular and molecular responses using imaging methods we identify the mechanisms that govern these behaviors. This ability to control cell behaviors at will and monitor dynamic responses in real time allow us to address questions that have been difficult to address using existing methods.
These subcellular optogenetic approaches can also potentially be used to for therapeutic control of specific cellular behaviors.
Castillo-Badillo JA, Bandi AC, Harlalka S, Gautam N. (2020) SRRF-Stream Imaging of Optogenetically Controlled Furrow Formation Shows Localized and Coordinated Endocytosis and Exocytosis Mediating Membrane Remodeling. ACS Synth Biol. 9(4):902-919.
Meshik X, O’Neill PR, Gautam N. (2019) Physical Plasma Membrane Perturbation Using Subcellular Optogenetics Drives Integrin-Activated Cell Migration. ACS Synth Biol. 8(3):498-510.
O’Neill PR, Castillo-Badillo JA, Meshik X, Kalyanaraman V, Melgarejo K, Gautam N. (2018) Membrane Flow Drives an Adhesion-Independent Amoeboid Cell Migration Mode. Dev Cell. 46(1):9-22.
*Article highlighting paper above: Bell GRR, Collins SR. (2018) “Rho”ing a Cellular Boat with Rearward Membrane Flow. Dev Cell. 46, (1)1-3.
Meshik X, O’Neill PR, Gautam N.( 2018) Optogenetic Control of Cell Migration. Methods Mol Biol. 1749:313-324.
O’Neill PR, Kalyanaraman V, Gautam N. (2016) Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration. Mol Biol Cell. Mol Biol Cell. 27(9):1442-50.
* Mol Biol Cell. Highlighted article
O’Neill PR, Gautam N (2015) Optimizing optogenetic constructs for control over signaling and cell behaviours. Photochem Photobiol Sci. 14:1578-85.
Karunarathne WK, O’Neill PR, Gautam N (2015) Subcellular optogenetics – controlling signaling and single-cell behavior J Cell Sci 128:15-25.
O’Neill PR, & Gautam N. (2014) Subcellular optogenetic inhibition of G proteins generates signaling gradients and cell migration. Mol Biol Cell. 25(15):2305-14.
* Mol Biol Cell. Highlighted article
* 24th annual MBoC Paper of the Year Award, American Society of Cell Biology.
O’Neill PR, Giri L, Karunarathne WK, Patel AK, Venkatesh KV, Gautam N. (2014) The structure of dynamic GPCR signaling networks. Wiley Interdiscip Rev Syst Biol Med. 6(1):115-23.
Giri L, Patel AK, Ajith Karunarathne WK, Kalyanaraman V, Venkatesh KV and Gautam N. (2014) A G protein betagamma subunit translocation embedded network motif underlies GPCR regulation of calcium oscillations. Biophys J. 2014 107(1):242-54.
Karunarathne, WK, Giri, L, Patel, AK, Venkatesh, KV, & Gautam, N (2013) Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration. Proc Natl Acad Sci USA. 110(17):E1575-83.
Karunarathne, WK, Giri, L, Kalyanaraman, V, & Gautam, N (2013) Optically triggering spatiotemporally confined GPCR activity in a cell and programming neurite initiation and extension. Proc Natl Acad Sci USA 110(17):E1565-74.
O’Neill PR, Ajith Karunarathne WK, Kalyanaraman V, Silvius JR, and Gautam N. (2012) G-protein signaling leverages subunit-dependent membrane affinity to differentially control βγ translocation to intracellular membranes. Proc Natl Acad Sci USA. 109 (51):E3568-77.
Saini DK, Ajith Karunarathne WK, Angaswamy N, Saini D, Cho JH, Kalyanaraman V, Gautam N. (2010) Regulation of Golgi Structure and Secretion by Receptor induced G protein βγ Complex Translocation. Proc Natl Acad Sci. USA 107(25):11417-11422.