Research Projects

Cell Membranes are complex interfaces that define a cell and its organelles from its environment. The constituents of membranes are dynamic in terms of lipid composition and their interacting partners, with a myriad of factors influencing the structure and dynamics of these interfaces. Multiple biophysical, biochemical, and computational studies have probed and gained insights into the proteins that are on the membrane's surface or embedded in it. While significant progress has been made in understanding membrane proteins and lipids, the role of nucleic acids as membrane-interacting partners is still largely unknown, leaving many questions unanswered. Current biophysical techniques, despite being cutting-edge, often yield low-resolution or ensemble-averaged data. Therefore, computational models are crucial for interpreting experimental results and gaining a deeper understanding of these complex assemblies. In the proposed project, I intend to understand the molecular grammar of RNA-membrane interactions using computational models integrating available experimental data. The aim is to answer the following questions using molecular simulations. We do know that messenger RNAs(mRNAs) contain signal sequences to localize the synthesis of the corresponding protein to specific organelles. Does the primary/secondary structure of mRNA provide enough information for robust localization onto the target membrane, or does the RNA need a specific tertiary structure to interact with the membrane? mRNAs, being relatively flexible macromolecules compared to proteins, adopt a diverse ensemble of conformations. How do such dynamic mRNA molecules maintain their specificity to target organelle despite the molecular noise in the cytoplasm? Is the translational efficiency of cytoplasmic mRNAs correlated with their affinity toward cellular membranes? Can we use the insights from the former questions to develop design principles for efficient lipid-based RNA delivery systems? RNA world hypothesis: With increasing evidence suggesting a possible origin of life from RNA molecules, understanding RNA-membrane interactions might provide us with clues to the formation of primitive protocells in the prebiotic era that might have led to the formation of the first forms of life on Earth. The initial phase will focus on developing an efficient computational model for simulating molecular-scale RNA-membrane systems. I then plan to use the developed model to set up multiple computer simulations of membranes containing different lipid compositions mimicking the membranes of the cellular organelles and different RNA sequences designed to mimic messenger RNA molecules in cells. The proposed work would provide us with insights into the RNA-membrane interactions and their role in mRNA localization. The outcomes would allow us to propose experimentally testable synthetic lipid vesicle-RNA systems that would allow us to determine principles for efficient lipid-based RNA delivery systems.