The Search for a Food-Borne Pathogens Achilles Heel
Most professors' research guides what they teach in their courses. That is not always the case for Shannon Hinsa-Leasure, professor of biology. Hinsa teaches about powerful gene editing technologies such as CRISPR but had not used them in her research. She decided to change that. Once you do it, you understand it a lot better, she says. As a result, the students involved in her research directly and those taking her courses are becoming better prepared to solve todays greatest scientific challenges.
Reducing a Pathogens Pathogenicity
Hinsa began a collaboration with Lilly Radoshevich 04, University of Iowa assistant professor of microbiology and immunology, who researches the bacteria Listeria monocytogenes. Listeria can contaminate uncooked foods such as deli meats, soft cheeses, and produce. When humans and other animals consume those foods, Listeria can escape their immune systems and secrete proteins that enable them to enter the hosts cells. The resulting disease, listeriosis, has symptoms ranging from mild stomach and intestine inflammation to brain inflammation, spontaneous abortion, and death. Approximately 2030% of people with listeriosis die.
There are seven lineages of Listeria. Hinsas team decided to focus on two: F2365, which causes more disease in humans, and EGD-e, which causes more disease in other animals. They nicknamed them Freddie and Eddie.
Our long-term goal is to identify the proteins that are key for one lineage causing more disease in humans and the second lineage causing more disease in animals, says Hinsa. Her team and Radoshevichs lab will also investigate how the immune system responds to each lineage. This research will help lay the foundation for targeted therapies to block the proteins that enable Listeria to cause listeriosis.
Learning as They Go
Hinsas team began by identifying the proteins that Listeria secretes. Listeria normally only secretes these proteins inside of a host. The Radoshevich lab, however, has Listeria strains that act as if they are always inside of a host, which makes studying the secretions possible. Two researchers in the lab, Emma Luhmann 18 and Madeleine Vessely 20, then used an analytical tool, mass spectrometry, to identify the proteins and quantify their amounts.
In the summer of 2021, Elle Adams 22 and Lauren Ellingsberg 22 selected four of the proteins that Luhmann and Vessely had identified. They selected proteins with unknown functions that were secreted significantly more in one strain than the other. By blocking those proteins and studying how Listeria functions without them, Hinsas team will discover whether they are key for Listeria to cause listeriosis.
First, Hinsas team tried using CRISPR to edit the genes that create the proteins so that the genes create less of them. This approach was not working, so they are trying another: moving a DNA molecule, a plasmid, to Listeria from which they removed the genes that create the proteins.
After Hinsas team successfully removes the genes, they will study whether Listeria that do not secrete the proteins infect and kill hosts at the same rate that normal Listeria do. They will begin with cell cultures and then move to mice. If the cells and mice respond better to the mutated Listeria than the normal Listeria, this research could be an important step in treating listeriosis. If they do not, there are plenty of other proteins to explore.
簫簫簫
Hinsa has a deep understanding of bacteria and immunology. These specific techniques of studying them, however, are almost as new for her as they are for her students. She says, We are learning as we go. I think one of the best ways to learn is to be in that environment where you dont have somebody who knows every step youve done wrong and tells you, but youre brainstorming and working through it together.
Vishva Nalamalapu 20 is the content specialist fellow in the Office of Communications and Marketing at 51勛圖. She loves writing about scientific research in a way that is accessible and interesting to readers with or without science backgrounds. Her series on scientific research projects focuses on doing just that. If you are a 51勛圖 professor or student interested in having your scientific research project featured or think someone elses project would be a good fit, please contact her.