Molecules and materials used in medical applications make intimate contact with our cells and tissues. This is true for pharmaceuticals commonly administered to patients, through to metal implants used in reconstructive surgery. These contacts between manmade materials and natural, biological systems are poorly understood, and difficult to probe and optimize. For example, medicines can have off-target effects, and implants can cause unwanted rejection or scarring. These interfaces must be better understood and optimized to correctly target tissues for better therapies. This project will develop new strategies for understanding how materials interact with cells. Specifically, to find fundamentally new methods for delivering gene based therapeutics to diseased tissues. Students will be exposed to a grand challenge in medicine, biology, materials science and chemistry, while working specifically on advanced polymers and biochemical screening techniques applicable to the study of many types of systems. Through interdisciplinary collaborations, the team seeks to impact both the field of biomaterials broadly, but also highlight the positive outcomes of working outside of normally well defined fields of study to bring different ways of approaching hard problems together in the lab to effect change.
Gianneschi and coworkers have developed nanoparticles that serve to protect DNA from enzymatic degradation while facilitating cellular entry and are able to modulate mRNA levels in live human cells with no appreciable toxicity. This development represents a significant advancement towards non-toxic nucleic acid delivery systems that can be synthesized by simple protocols. However, as with many other biologically active nanomaterials, the mechanisms underlying, cellular uptake, endosome escape, mRNA regulation and nuclease resistance are not understood. This project's goal is to develop a universally applicable method that will allow researchers to understand the mechanisms involved in nanomaterial uptake by cells. This will also enable identification of potential bottlenecks that are associated with nanomaterial function and facilitate optimization of materials for downstream applications. Through a combination of advanced gene-editing tools and materials synthesis, new uptake pathways will be discovered, optimized, and then utilized to modulate gene expression allowing several routes towards treatment of disease including the sensitization of cells to therapies to which they are otherwise resistant. The proposed work is a fundamental biomaterials investigation of new structures, and new biological interfaces.