Soft materials like lipids are important components of biological systems and have numerous technological applications. Using organic synthesis, we will access two classes of soft materials which have remained little explored till date - namely, sponge phase forming lipids and archaeal bipolar tetraether lipids. The materials will be characterized using techniques such as small-angle X-ray scattering, differential scanning calorimetry, and electron microscopy. Based on the novel soft materials, we will develop artificial cellular systems, drug delivery vehicles, and membrane protein reconstitution tools.
A cell-free protein synthesis (CFPS) system can be thought of as a deconstructed cell cytoplasm where proteins can be rapidly expressed by simply adding the DNA encoding those proteins. CFPSs offer many advantages over cell-based protein expression – quick design-build-test cycles, ease of storage, facile incorporation of unnatural amino acids, expression of proteins that are toxic to cells. We will focus on cell-free synthesis of membrane proteins and in situ purification and reconstitution into novel lipidic assemblies for downstream biophysical and structural biology applications.
Viruses are the most numerous biological entities on Earth. They are known for regulating genetics and causing pathogenesis as intracellular parasites in all three domains of life. Bottom-up biophysical models can provide useful insight into mechanistic details of molecular functions and interactions in key viral processes and pathogenesis. Fundamental understanding of viral processes is also key to designing lipid nanoparticles and viral vectors with improved efficiency of intracellular delivery. Using advanced fluorescence microscopy techniques, we will work on various problems involving membrane fusion and/or remodeling by enveloped viruses, viral vectors, and lipid nanoparticles.