From ‘gut brains’ to supply chains, PhD students tackle complex problems

02/16/18 – BOSTON, MA. – Marissa Puzan, PhD’19, earning her doctorate in chemical engineering, conducts research in the Mugar Life Sciences Building on Feb. 16, 2018. Photo by Matthew Modoono/Northeastern University

Marissa Puzan, PhD’19, is earning her doctorate in chemical engineering and has an interest in mental health. She’s developing a tissue-engineered model of the intestine—specifically the first intestinal layer, which comes into direct contact with food, metabolites, and bacteria.

Puzan is investigating how neurons—specialized cells that send information—under that first intestinal layer talk to one another. She’s built a membrane platform using intestinal stem cells from patients at Boston Children’s Hospital. Doctors there derive the stem cells from biopsies and send them to Puzan, who then extracts only the neurons from the group of cells to build her model.

The majority of humans’ neurons are in our brains, but scientists are increasingly interested in better understanding the massive number of neurons in the intestine, which Puzan said many researchers refer to as the “brain in the gut.” Ultimately, Puzan’s goal is to understand how our diets change the neural chemistry of our brains.

“People have already started to show that what you eat can affect your mood or cognition. Gastrointestinal symptoms and irritable bowel disease and things like that often accompany mental disorders like depression and anxiety,” Puzan said. “I’m most interested in how intestinal contents can alter how you think.”

Puzan is among the nearly 50 doctoral students in the College of Engineering who will present their work at the PhD Research Expo as part of Engineers Week at Northeastern. The expo—scheduled from 8 a.m. to 12:30 p.m. in the Curry Student Center Indoor Quad—will feature work in areas ranging from robotics to resilient infrastructure to cell tissue engineering.

Shaping better drugs

Nathan Harms, PhD ’20, is also a chemical engineer. But his research focuses on three-dimensional molecules—for example, those that make up pharmaceuticals. Harms is examining how the different shapes and conformations of these molecules lead to different reactions in the body.

“There is a case where one orientation of a drug prevents morning sickness in pregnant women, but another orientation of it causes huge birth defects in the children that are being born,” said Harms. “Understanding the 3D geometry of these molecules is very important.”

The problem is that it’s tedious and time-consuming to figure out the shape of a large, complex molecule. To make that process more efficient, Harms is using two methods— genetic algorithms and evolutionary strategies—to develop a computational tool that can be applied to a variety of different molecules. Currently, he is verifying his tool by testing it on the anti-cancer drug Paxol and seven common amino acids. The orientations of Paxol and these amino acids are already known, so Harms will be able to test and confirm that his tool works.

Optimizing drug delivery

Rana Azghandi, PhD’18, is also interested in pharmaceuticals. But as a student earning a doctorate in industrial engineering, she is focused on the supply chain that gets these drugs to people who need them.

Azghandi said that many of the recent drug shortages we’ve seen in the United States cannot be blamed on a single event or factor. Recalls can halt the production of drugs. Sometimes manufacturers shut down for inspection, which can also lead to shortages down the line. These examples are called exogenous shocks, and Azghandi’s research is showing that the ways in which a company responds to them are important for maintaining a robust supply chain.

There are several potential solutions to preventing drug shortages. The company could build additional manufacturing capacity or redesign its entire supply chain, for example. But for pharmaceuticals with low profit margins, the company may not be adequately incentivized to take these actions. Instead, Azghandi’s research, which uses system dynamics methods, has found that the best policies for avoiding drug shortages are those that evolve with each specific type of disruption.

“It’s best to look at the behavior of the supply chain to see how it will react to exogenous shocks, and evaluate static and adaptive policies based on those observations,” Azghandi said.