Extrinsic control of neural activity is a powerful way for understanding how neural circuits regulate behavior. The standard way is using optogenetic tools to activate or inhibit neuronal activity with light. However, it has its own limitations that does encourage researchers to look for  a modality for extrinsic activation of the nerve cells outside of light. Temperature as a new modality and Thermogenetic tools provide an ideal complementary approach to optogenetics. A good candidate for developing new thermogenetic tools is the Drosophila gustatory receptor (Gr) 28b family, which has been implicated in high-temperature avoidance behavior. My work provide information regarding the biophysical characteristic of this protein. 

I addressed the questions regarding the ionic selectivity of Gr28bD and its temperature sensitivity. To expand the pool of potential candidates for thermogenetic tools and looking for clues in structure/function studies of this channel we investigated and identified six orthologs of Gr28bD as new thermosensitive proteins. Our team successfully modeled a computational structure of this channel and our model suggested that Gr28bD forms a homotetramer structure. Looking for the pore and thermosenseing domain of this protein, I identified several residues as target for mutation screening of Gr28bD. The results revealed information on contribution of these residues in Gr28bD structure/function. 

Publications

Mishra, A., Salari, A., Berigan, B.R., Miguel, K.C., Amirshenava, M., Robinson, A., Zars, B.C., Lin, J.L., Milescu, L.S., Milescu, M. and Zars, T., 2018. The Drosophila Gr28bD product is a non-specific cation channel that can be used as a novel thermogenetic tool. Scientific Reports, 8(1), pp.1-10.

Navarro, M.A, Amirshenava, M., Salari, A., Milescu, M., and Milescu, L.S. (2022) Parameter optimization for ion channel models: integrating new data with known channel properties. IN: Vanhaelen, Q. (Ed), Computational Methods for Estimating the Kinetic Parameters of Biological Systems. Springer Press. 

Committee

• Dr. Pamela Brown, Chair
• Dr. Mirela Milescu
• Dr. Lorin Milescu
• Dr. T.-C. Hwang