INDIANAPOLIS – It happened by accident.
Jeremy Johnson, Butler University Associate Professor of Chemistry, was looking at images of acyl protein thioesterases, or APTs. Because proteins are smaller than the wavelength of light, they cannot be seen by eye, or even with a microscope. So, proteins are crystalized, and then static images are taken, revealing what they look like at one point in time.
But, when Johnson looked at the APT images closely, he saw something he had never seen before, and something, he says, that is quite rare – the protein in multiple states.
“Our image showed the APT in open and closed states or active and inactive,” Johnson says. “Normally, we think of proteins as static, or as staying in one position, and only recently have we started to appreciate the idea of natural movements of proteins.”
With an $250,000 grant from the National Science Foundation, Johnson will be researching why we should appreciate that very idea. Seeing the image of the APT in a dynamic state enabled Johnson to hypothesize a whole new set of ideas about what this protein could potentially impact – cancer progression, neural deterioration, and immune functions, he says.
“Once we had this image and saw it was dynamic, we were able to start to hypothesize how this protein could be important within a cell,” he says. “All of a sudden new possibilities emerged that we knew we wanted to research more. Once we knew the structure, new alleys for research questions opened.”
APTs are a class of enzymes that are linked with cancer growth, neural degeneration, and bacterial infections. But, this photo revealed they are also dynamic – something that was not previously known.
Now, Johnson says, he is set to dive into what this dynamic function actually means, and how it could impact those important links. Some questions his lab will focus on include looking at how the dynamic nature of this protein could impact APTs as a future drug target, and how it might relate to cancer and immune functions.
After seeing the image, Johnson says his team will start to look into how that movement is related to the regulation of the protein and how that can impact the biological functions of APTs.
“You always hope there is relation to the big picture,” Johnson says. “We are going to be looking at the dynamic movement and if that movement is essential to biological function. You hope that movement is related to the big picture things that we know this protein is already involved in.”
Also, as part of the NSF grant, research occurring in Johnson’s lab will be integrated into undergraduate classroom laboratories, giving a wide range of students the chance to participate in the research. There will also be a new molecular biophysics laboratory added to the biochemistry major at Butler.
All of this, Johnson says, because of an accident.