Preventing Freezer Burn and Saving Human Tissue

It sounds simple, but Shah Razul’s work involves trying to understand what water molecules do when they get to below zero degrees Celsius because the possibilities that understanding offers  could be life-changing. 

When water crystallizes, its volume increases and it forms a regular structure that destroys, for example, cells, or, in the case of an organism, its delicate membranes and systems. As most of us will know, when food is frozen and we leave it too long, the ice separates out, leaving the food “freezer burned.” A wasted chicken breast is one thing, but this problem also exists, for example, in cryopreservation of cells, tissues and organs.

“When water’s in a close-to-frozen state, it has some interesting behaviour,” says Razul, an associate professor of chemistry at St. Francis Xavier University. “We’re trying to understand what the water molecules are doing.”

Razul’s overarching goal is to find a way to keep water from forming crystals and then applying that learning to real-world problems in areas such as food and health care. 

“If we can, we can solve many problems related to freezing,” he says, including, for example, potentially creating environmentally safer antifreeze products to replace or minimize the use of road salt. 

He looks to creatures such as the wood frog, which uses glucose to stop the freezing process from destroying its tissues in winter. Razul, therefore, is running simulations to look at the process of freezing and analyze what water molecules are doing in the fractions of a second just before they form crystals and freeze. 

“A lot of my work now is involved with understanding how small biomolecules, such as different kinds of sugars and salts, stop water from freezing or slow down the process,” he says, adding that he wants to figure out a biomolecular combination that would achieve this goal. 

Over the past five years, he’s been using computational principles to develop a cryoprotectant to preserve lobster meat. 

“We’ve tried it and it works,” he says, adding that some companies from overseas are testing his system currently. “We had a taste test in Atlantic Canada, and we’ve published a couple of studies where the public indicated that it tastes as if it was cooked yesterday, preferring it to  frozen lobster meat that is sold currently.” 

His next frontier is looking at the ways in which his process can preserve muscle cells and brain cells to see what kind of applications it might have in the healthcare field.

“No one has a definitive answer to how these cryoprotectants work at the molecular level,” he says. “It’s basically all trial and error. We try a little bit of this and a little bit of that and see whether it works.” 

To do his work, he’s watching the behaviour of water in minute detail — fractions of seconds — and then he replicates the test multiple times. 

“Because of that, I generate a lot of data,” he says, and that’s why he couldn’t do his work without ACENET’s high performance computing. 

“It’s almost impossible to do this work without ACENET,” he says. “I would need a year and a half to do it sequentially as opposed to one month with ACENET.” 

Developing Artificial Lung Surfactant

Lung surfactant is a material that lines the air-sacs in the lungs and is essential for breathing. Premature babies are often born before they have a chance to produce sufficient lung surfactant and they need to be given surfactant in order to help them breathe. This surfactant is generally sourced from animals. People of any age who are seriously ill or injured also frequently have damage to their lung surfactant, which impairs their ability to breathe. One such condition, called Acute Respiratory Distress Syndrome (ARDS), affects 150,000 people per year in the US, and has a fatality rate of about 40%. Unlike with premature babies, treating adults with surfactant derived from animals has been very challenging for two reasons. First, adult lungs are larger than a baby’s and it’s therefore difficult to get enough animal surfactant together to cover it. Second, there are hostile conditions present in the lungs of ARDS patients that deactivated their own lung surfactant, and that rapidly inhibits surfactant. Dr. Valerie Booth is working with a multi-disciplinary team at Memorial University and a research team in Spain to understand the essential features of the proteins in natural lung surfactant and to use this knowledge to develop artificial lung surfactant treatments that are more resistant to deactivation. Specifically, Booth’s research focuses on Surfactant Protein B (SP-B). SP-B is of particular importance because unlike the other lung surfactant proteins, you absolutely can’t live without it in your lungs. Furthermore, unlike most essential proteins, we strangely do not know the three-dimensional structure of SP-B, or what it looks like. Consequently, we don’t understand how it works. This is because SP-B is exceptionally hard to work with experimentally. SP-B is very hydrophobic, a fancy word for sticky. It likes to stick to greasy, lipid molecules instead of to water. Despite the challenges, it is possible to use experimental techniques to find out small pieces of information about its structure. However, the key to unlocking SP-B’s molecular structure is through running simulations on Compute Canada infrastructure. Booth’s group uses these simulations to make predictions about what SP-B looks like, and then compares those to the experimental data in order to provide the best possible picture of SP-B. Proteins are like tiny molecular machines and we can’t figure out how they work until we know what they look like. Determining what SP-B looks like tells researchers how it works. Understanding how we breathe will help Booth develop a treatment for ARDS. In fact, she, two of her PhD students and a research assistant are currently working towards a provisional patent for a formulation for artificial surfactant, with the hope it will result in an industrial partnership. _Illustration courtesy of Mohammad Hassan Khatami_