colorized microscope images of fetal intestine and three intestinal organoids grown in different media

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Discovery research updates

Summer 2022
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An Easier Way to Grow Model Organs

In recent years, scientists who study how the human body develops and functions on the most basic level have enjoyed a renaissance of sorts, thanks to structures called organoids – tiny 3D models of organs developed from pluripotent stem cells that grow in petri dishes. However, growing tiny organs in a dish is a tricky process.

A U-M lab, headed by Jason Spence, Ph.D., the H. Marvin Pollard Collegiate Professor of Gastroenterology and professor of cell and developmental biology and of biomedical engineering, has developed a significantly simpler way of cultivating a 3D model of the intestine. A paper published in Cell Reports in February describes the lab’s successful generation of the human intestinal organoid in a simple suspension culture.

They compared the suspension organoids to actual human tissue, as well as to organoids formed using more conventional growth environments, and found that they looked similar at the molecular level. In fact, the suspension organoids more closely resembled the actual human tissue. The team hopes that suspension culture will open up the possibility of larger-scale organoid experiments and will be an improved system to study human development and disease. —Kelly Malcom

 

Hidden Gem Enables Gene Editing with Novel CRISPR-Cas3 System

For nearly a decade, scientists have been using CRISPR, a tool employed by bacteria to protect themselves against viral invaders, to edit genomes. But one of the most popular CRISPR tools, CRISPR-Cas9, is limited in its ability to make large-scale, gene-size edits, says Yan Zhang, Ph.D., assistant professor of biological chemistry.

In 2019, Zhang’s lab was one of the first to describe CRISPR-Cas3, a tool that could handle large-scale genome deletions. But that tool was also limited, particularly in its efficiency. The team developed N. lactamica CRISPR-Cas3, and were able to achieve much greater editing efficiency. They set out to establish an expression method using plasmids, the small circular DNA molecules that researchers can use to circumvent the protein purification step, but it didn’t work.

Then Ph.D. student Renke Tan noticed an extra unexpected protein band on the protein purification gel, and eventually figured out that it is an internal translation product, Cas11, without which the CRISPR-Cas3 complex would not form. With the publication of their work in Molecular Cell last January, the team has made the tool available on Addgene, allowing researchers to investigate a wide range of scientific questions, from deleting large, disease-causing genes to studying the non-coding human genome. —KM

 

The Link Between Lung Fibrosis and Bacterial Infection

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by excessive scarring (fibrosis) of lung tissue. This scarring prevents the lungs from functioning properly, making it difficult to breathe. Bacterial infections make it worse, and IPF patients are particularly susceptible to them. However, what underlies this susceptibility is largely unknown.

It is unclear whether “the mechanics of their lungs don’t work anymore, thus trapping bacteria in the lung, or if there is an alteration in their immune response,” says Bethany Moore, Ph.D., Chair of the Department of Microbiology and Immunology. Moore is senior author of a study published in JCI Insight last February that suggests the latter — that lung scarring could compromise the immune system.

“This study addresses a long-held conundrum in the IPF field.” The findings could ultimately alter the treatment regimen and behavioral habits of those living with IPF. —Madeline Barron