Breakthroughs on the Molecular Level: Biophysics Research at the University of Guelph

Posted on Wednesday, May 26th, 2021

Written by Michael Stuck & Callum Stonehouse

The University of Guelph’s Department of Physics offers several areas of graduate study in biophysics, including the Photobiophysics Research Group, led by Professor Leonid Brown, and the Protein Nuclear Magnetic Resonance (NMR) Research Group, led by Professor Vladimir Ladizhansky. Both Brown and Ladizhansky have been professors at the university for nearly 20 years. 

Brown’s Photobiophysics Group studies light-sensitive membrane proteins. These are proteins within cellular membranes that interact with light to create chemical energy (a phenomenon studied by a branch of biophysics called bioenergetics) or a cellular signal, for example, in vision. 

“We use computational bioinformatics techniques to find new, interesting proteins,” says Brown of the work his group does. “Then we make those proteins using microbiological and biochemical methods, and characterize them with all kinds of physical and chemical techniques.” 

One such technique that's used is Fourier Transform Infrared (FTIR) spectroscopy, which measures how much infrared light is absorbed by a sample at different wavelengths. The amount of electromagnetic radiation absorbed at each wavelength depends on the molecules in the sample, so measuring the absorption of light can be used to both identify and characterize organic materials. 

One of the University of Guelph’s FTIR spectrometers (left), as well as an example of the FTIR difference spectrum of a membrane protein, produced by illumination.
One of the University of Guelph’s FTIR spectrometers (left), as well as an example of the FTIR difference spectrum of a membrane protein, produced by illumination. (photos, from left to right:[1], Harris et al; credit to Andrew Harris and Leonid Brown[2])

Professor Ladizhansky’s research group, meanwhile, is most interested in developing NMR spectroscopy techniques[3] to identify organic compounds and explore atomic interactions of biological molecules, getting detailed views of molecular structures. With these methods, the researchers are even able to “see” each atom within the molecule.

Two of the university’s seven NMR spectrometers.
Two of the university’s seven NMR spectrometers. (photo:[4])

For Ladizhansky, the group’s work embodies why he developed an interest in biophysics, which happened shortly before he came to Guelph. “I became very interested in biology because to me, we are trying to solve problems that are created by nature, as opposed to by humans. I think that it’s much more challenging, and the challenge is what really drives me.”

The research led by Brown and Ladizhansky is highly related, leading to extensive collaboration between the two and their teams. 

Recently, both teams brought their skill sets together for a study of membrane protein folding. Folding is a process in which the chains of amino acids that make up proteins fold into well-defined three-dimensional shapes, and the resulting structure is key to defining its function. By understanding how proteins fold—and why they sometimes misfold—we can gain a better understanding of the causes of several diseases. For example, α-synuclein, a protein found in brain tissue, is known to cause Parkinson’s disease when misfolded versions accumulate. 

The sequence of steps in the folding process is often quite elaborate, making this an exciting challenge. Working together, Brown and Ladizhansky have made significant in-roads, reporting high-resolution observations of the sequential steps in protein unfolding, which gives some insight into the complex folding process[5].

A 3D model of a sensory rhodopsin protein obtained by NMR spectroscopy.
A 3D model of a sensory rhodopsin protein obtained by NMR spectroscopy,
one of manymolecules which the Biophysics groups study.
(photo: Wang et al; credit to Shenlin Wang and Leonid Brown[6])

Brown and Ladizhansky are both deeply committed to engaging undergraduate students in cutting-edge research. Both professors supervise undergraduate research positions almost every summer, allowing for many research opportunities for students. “We are proud of our record,” says Brown. “I would say that almost every undergrad who has worked with us ended up with their names on published papers, and some on several.” For example, students working with Brown recently discovered new, previously unstudied proteins[7].

Brown and Ladizhansky have found that the wide-ranging research their groups conduct is often attractive to prospective graduate students. “There are many different projects that can be offered to grad students with diverse interests,” says Ladizhansky. “It can be anywhere from quantum mechanics, when it comes to the development of new NMR techniques, all the way to more biochemically oriented projects where you have to express proteins, purify them, and characterize them using a variety of different methods.”

The work being done in this area at the University of Guelph is on the cutting edge of modern physics. “We are trying to do new things which nobody has ever done, both biologically and spectroscopically,” says Brown. “We are trying to go to uncharted territory, because this is what’s exciting.”

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