Title/s: Assistant Professor
Office #: FH-212
Postdoctoral Associate, 08/2017-08/2022, (Biophysical Chemistry, Biochemistry, neurobiology) Sanford Burnham Prebys Medical Discovery Institute, San Diego, CA
Ph.D. in Physical Chemistry, 08/2012-06/2017, Indiana University, Bloomington, Indiana
M.Sc. in Chemistry, 08/2006-7/2008, University of North Bengal, India
We will investigate the native biological interactions of lipids that are possibly responsible in different diseased conditions, particularly focusing on neurodegenerative disorders. Through the following projects, our research will adopt different strategies to investigate such lipids, their interactions with cognate G-protein coupled receptors (GPCRs), by maximizing the preservation of their in vivo conditions.
Project 1: Native Nanodisc approach to study interactions of lipids
Native nanodisc is a detergent free approach to extract the native inherent lipid composition, proteins of a membrane by directly extracting the membrane from cell lysates by using synthetic polymers into small nanodiscs. These isolated intact nanopatches of biological membrane are highly thermostable particles, suitable for spectroscopic studies and hence, will provide a unique opportunity to investigate the preferential interactions of the immediate local lipid environment with the membrane proteins.
Project 2: Development of Compensated Interferometric Reader (CIR) towards achieving its universal and high performance in measuring various biological interactions
CIR is a benchtop refractive index (RI) reader that uses a label free, Free Solution Assay (FSA) to measure the biological interactions from nanoliter volume of sample with a sensitivity from 10-7 to 10-9 RIU. Through collaborative efforts we are interested in exploring this technology beyond its current limited application to challenging biological interactions involving lipids, synthetic peptides, antibodies, and enzymes. This project will require development of binding assays, along with instrumentation as required for the various projects.
Project 3: Biased signaling mechanism in GPCRs
The highly dynamic GPCRs possesses allosteric binding pockets, in addition to orthosteric binding pocket where the native ligands bind. While orthosteric pockets are important to undergo intracellular responses in normal physiological changes, probing allosteric pockets are important to inhibit the intracellular signaling causing disease mechanisms. In this project, we will measure such allosteric interactions, perform computational modelling (in collaboration) to determine the allosteric structural features which will be important to discover novel molecules with therapeutic effects.
N. Khiar-Fernández, ‡ D. Zian, ‡ H. Vázquez-Villa, R. F. Martínez, A. Escobar-Peña, R. Foronda-Sainz, M. Ray, Puigdomenech-Poch, G. Cincilla, M. Sánchez-Martínez, Y. Kihara, J. Chun, R. López-Vales, M. L. López-Rodríguez, * and S. Ortega-Gutiérrez* “A novel antagonist of the type 2 lysophosphatidic acid receptor (LPA2), UCM-14216, ameliorates spinal cord injury” J. Med. Chem. 65, 16, 10956-10974 (Aug 2022)
S. Liu†, N. Paknejad†, L. Zhu, Y. Kihara, M. Ray, J. Chun, W. Liu, R.K. Hite, and X-Y. Huang, “Differential Activation Mechanisms of Lipid GPCRs by Lysophosphatidic Acid and Sphingosine 1-Phosphate” Nat. Commun 13, Article number: 731 (Feb 2022)
Ray, K. Nagai, Y. Kihara, A. Kussrow, M. N Kammer, A. Frantz, D. J. Bornhop and J. Chun. “Unlabeled Lysophosphatidic Acid (LPA)-LPA1 Receptor Binding in Free Solution Determined by a Compensated Interferometric Reader”, J. Lipid Res. 61(8), 1244-51 (Jun 2020)
Ray, A. Saha, and K. Raghavachari, “Hydrogen Evolution from Water using Mo-Oxide Clusters in the Gas Phase: DFT Modeling of a Complete Catalytic Cycle using Mo2O4̄/Mo2O5̄ Cluster Couple”, Phys. Chem. Chem. Phys., 18, 25687 (Aug 2016)
H. Mizuno, Y. Kihara, A. Kussrow, A. Chen, M. Ray, R. Rivera, D.J. Bornhop and J. Chun, “ Lysophospholipid G protein-coupled receptor binding parameters as determined by backscattering interferometry,” J. Lipid Res. 60(1), 212-7 (Jan 2019)
Ray, J. Felton, J.O. Kafader, J. E. Topolski and C. C. Jarrold, “Photoelectron Spectra of CeO‾ and CeO2H2‾”, J. Chem. Phys., 142, 064305 (Feb 2015)
J. Felton, M. Ray, and C. C. Jarrold, “Measurement of the electron affinity of atomic Ce,” Phys. Rev. A 89 (3), 033407 (Mar 2014)
Publication list via Manisha Ray