Recognizing the urgent clinical need for synthetic vectors, Ramya implemented an unbiased materiomics approach to polymer-mediated gene delivery. She faced two obstacles: 1) the intricacies involved in the rapid synthesis of precisely designed polymers through controlled radical polymerization techniques and 2) the paucity of experimental platforms that unite throughput, analytical rigor and precision.
Rational polymer design is impeded by the “curse of dimensionality” since elucidation of the mechanistic roles played by numerous design variables such as polymer composition, architecture, length and formulation parameters is confounded by non-linearities. Intuition-based methods of pattern recognition and traditional hypothesis-testing statistical frameworks cannot alleviate challenges arising from a complex multidimensional design space.
Ramya has extensively employed data-driven approaches to map relationships between polymer properties and biological responses, such as proliferation rate, cellular uptake, toxicity and delivery efficiency. She is interested in establishing high-throughput experimental (HTE) workflows for biomaterial discovery and in applying statistical learning methodologies on large experimental datasets to derive structure-activity relationships.
Ramya is deeply interested in investigating physical pathways for polyelectrolyte complexation (or polyplex formation) by integrating particle engineering, polymer chemistry, and process intensification. This modular approach will create multidimensional libraries of nanoparticles wherein particle morphology and size distribution will be decoupled from the surface composition.
The nexus between the interfacial properties of stem cell culture substrates and the physicochemical attributes of polyplexes is yet to be probed methodically. Ramya proposes to explore the interplay between surface chemical cues and polyplex properties by transfecting iPSCs cultured on surface-engineered substrates of diverse chemical functionalities and brush architectures.
During Ramya’s PhD, she elucidated design rules for virus-resistant coatings by employing glycocalyx-mimetic polymer brushes as model surfaces to study viral bioadhesion. The role of the glycocalyx in viral invasions is not well-understood because some components of this biological barrier function as receptors for viruses while others block viral entry.
Spatioselective deactivation of ATRP initiator coatings made via chemical vapor deposition polymerization was demonstrated to synthesize micropatterned polymer brushes in a substrate-independent, modular and facile manner. Exposure of 2-bromoisobutyryl groups to UV light resulted in the loss of the bromine atom and effectively inhibited polymer brush growth.