Science and technology

That feeling in your gut? It’s molecular crossbows firing!

UM researchers are studying the mechanism of how Gram-negative bacteria use the T6SS as a weapon.

Group photo of the research group from left to right, Matthew Van Schepdael, Gerd Prehna, Kartik Sachar, Mazdak Khajehpour, Andrew Gierys, Iman Asakereh
Estimated Read Time:
2 minutes
From left to right: Matthew Van Schepdael, Gerd Prehna, Kartik Sachar, Mazdak Khajehpour, Andrew Gierys, Iman Asakereh.
From left to right: Matthew Van Schepdael, Gerd Prehna, Kartik Sachar, Mazdak Khajehpour, Andrew Gierys, Iman Asakereh.
Estimated Read Time:
2 minutes

Bacteria, such as E. coli and Salmonella, use a microscopic crossbow-like weapon known as the Type VI Secretion System (T6SS) to fire toxic proteins into neighbouring cells in our guts. Many Gram-negative bacteria use the T6SS to fight other bacteria, regardless of whether they are human pathogens, animal pathogens, or even agriculturally important soil bacteria. But when it comes to us, the T6SS is a primary weapon of warfare between the good bacteria of our bodies and many bad bacteria that try to make us sick.

UM researchers are studying the mechanism of how Gram-negative bacteria use the T6SS as a weapon.

Problem solver

University of Manitoba PhD student, Matthew Van Schepdael, is the main author of a research paper that was recently published in the journal Nature Communications. In this study, Van Schepdael and others show how bacteria use ‘helper’ proteins (chaperones) to hold onto T6SS toxins safely, then let go at exactly the right moment while the T6SS crossbow fires. An understanding of these crucial mechanistic details will help researchers discover how to ‘jam’ the T6SS crossbow to mitigate its harmful effects. Furthermore, this understanding can also help researchers find ways to re-engineer the T6SS crossbow as a biotechnology and therapeutic tool.

Figures from the Biophysical characterization of Eag chaperones suggests the mechanism of effector transmembrane domain release research paper.
Matthew Van Schepdael, Gerd Prehna, Mazdak Khajehpour, Iman Asakereh discussing about the research.
Figures from the Biophysical characterization of Eag chaperones suggests the mechanism of effector transmembrane domain release research paper; Matthew Van Schepdael, Gerd Prehna, Mazdak Khajehpour, Iman Asakereh discussing about the research.

Van Schepdael is a member of the Prehna Lab in the department of microbiology, under the supervision of Dr. Gerd Prehna, an associate professor in the Faculty of Science. The Prehna Lab studies the biochemical, molecular, and structural details of how bacteria fight and talk with each other, and how they interact with other micro-organisms.

An important piece of this research was to understand the dynamics of how two proteins bind each other and then later let go of each other, in this case, the ‘helper’ chaperone and the T6SS toxin. Researchers usually need to isolate each protein individually, then recombine them to study protein binding dynamics.

Matthew Van Schepdael wearing an off-white sweater smiling at the camera.
Matthew Van Schepdael, University of Manitoba PhD student
The problem with this story is that we have two proteins, where one can be isolated alone, and the other is insoluble.

University of Manitoba PhD student, Matthew Van Schepdael

In response to this challenge, Prehna reached out to Khajehpour Lab in the department of chemistry in the Faculty of Science. The Khajehpour lab studies protein dynamics, biophysical methodology and applications in biochemistry, under the supervision of Dr. Mazdak Khajehpour, a professor at the Faculty of Science.

Iman Asakereh wearing a patterned sweater smiling at the camera.
Iman Asakereh, PhD student in Khajehpour Lab
Our approach was to look at the effect of work required to perturb the system from a stability standpoint to get an idea about how these two proteins [helper chaperone and T6SS toxin] interact with one another.

Iman Asakereh, PhD student in Khajehpour Lab

This is where the beauty of true scientific partnership appears, an innovative approach that allowed these two labs to reveal for the first time the intricate molecular and chemical details of how helper chaperone proteins let go of toxins while the T6SS crossbow fires.

Watch the full interview

To learn more about this collaboration and the research, please watch the full interview on the Faculty of Science’s YouTube channel.

By

Kimia Shadkami

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UM is home to researchers and scholars who respond to emerging issues and lead innovation in our province and around the world. Creating knowledge that matters is one of the strategic themes you’ll find in MomentUM: Leading change together, the University of Manitoba’s 2024–2029 strategic plan.