Developing a Computer Model for Improved Disease Understanding
ChE Assistant Professor Srirupa Chakraborty has been awarded a $1.99 million NIH R35 MIRA Award for Early Stage Investigators to design and develop a computational model for making biomaterials that function like mucin, a naturally occurring substance in the human body that serves as a protective layer on tubular organs and surfaces exposed to external environment.
Srirupa Chakraborty, assistant professor of chemical engineering, received a $1.99 million National Institutes of Health R35 Maximizing Investigators Research Award (MIRA) for Early Stage Investigators to design and develop a computational model for making biomedical materials that function like mucin—a naturally occurring substance in the human body that serves as a protective layer on tubular organs and surfaces exposed to external environment. The biomaterials developed with Chakraborty’s model, such as surgical glue or in drug delivery systems, would act as a protective layer, like mucin does naturally.
Mucin is made up of glycoproteins that are densely populated with sugars, and it helps prevent pathogens from reaching underlying tissue. For example, a mucin layer in the nose catches germs, bacteria, and debris that could harm the lungs.
“The mucin has so many very unique and interesting properties that they could be inspiration for many of our material needs,” Chakraborty says.
In order to design the model for biomaterials development, Chakraborty’s research team will enhance existing computational tools, which she says are limited, as well as develop new tools to investigate mucin at the molecular level.
The team will use a multi-modal approach for computational tools that will enable investigation of the mucin at different scales. They will use principles based atomistic modeling to capture the equilibrium structure-dynamics; biophysics-based coarse-grained methods to describe bulk properties and transitions; and data-driven machine learning approaches to predict topology and intermolecular interactions.
“Whatever we predict by computers should be a trustable model that could be scaled down to the atomistic level,” Chakraborty says.
The team will investigate how some molecules are able to outsmart the mucin layer and pass through, while others cannot.
As an example, the models could be the foundation to design a new type of surgical glue that would protect an open wound from pathogens. Because the surgical glue will have a molecular structure similar to mucin, the body will not reject it as a foreign substance.
The protective properties could be expanded to a range of opportunities, even acting as a membrane between clean water and foreign bodies, Chakraborty says.
In addition to the MIRA Award, Chakraborty received a $100,000 related grant with collaborator Nanite Bio, a biotech startup founded by Shashi Murthy, a former Northeastern professor of chemical engineering, to develop a drug delivery system for the specific treatment of Cystic Fibrosis. This secondary research grant will rely on findings from the larger research project to create a drug delivery system that could penetrate mucin membranes that have mutated and thickened, resulting in Cystic Fibrosis disease.
“We will be making materials inspired by mucin to be able to get through the thickened mucosal layer,” Chakraborty says. “We are going to piggyback on certain carriers that are present in those layers.”
R35 MIRA Awards from the NIH are designed to provide investigators with greater stability and flexibility, thereby enhancing scientific productivity and the chances for important breakthroughs.
Abstract Source: NIH