At the University of Chicago Pritzker School of Molecular Engineering (UChicago PME), researchers are revolutionizing new approaches to improve human health.
Much of the power of immunoengineering, one of UChicago PME’s research themes, lies in cross-disciplinary collaboration. UChicago PME shares faculty and conducts joint research with UChicago’s Biological Sciences Division, leading to new interdisciplinary innovations. The school also partners with scientists at Argonne National Laboratory, where new grants for synchrotron X-ray beam time and high-performance computing will help researchers better understand materials at the smallest levels and use AI to uncover new cancer drugs.
The Chan Zuckerberg Biohub Chicago — which funds high-risk, high-reward research linked to inflammation and the functions of the immune system — awarded $4.8 million to UChicago PME faculty teams to fund bold, early-stage projects.
Whether developing new technology or materials, or uncovering new functions of proteins and viruses, UChicago PME faculty are at the forefront of immunoengineering research. Here are few recent breakthroughs.
New hydrogel semiconductor for bioelectronics
Asst. Prof. Sihong Wang and his research group built a powerful semiconductor in hydrogel form that could be used for implantable bioelectronic devices and caring for wounds.
The bluish gel is soft and stretchable while retaining the semiconductive ability needed to transmit information between living tissue and machine. The gel could be used in pacemakers, biosensors, and drug delivery devices, and because the material is soft, it reduces the immune responses and inflammation typically triggered when a medical device is implanted. The new porous material also enables elevated biosensing response, resulting in more efficient wound healing. The research was published in Science.
“It has very soft mechanical properties and a large degree of hydration similar to living tissue,” Wang said. “Hydrogel is also very porous, so it allows the efficient diffusion transport of different kinds of nutrition and chemicals. All these traits combine to make hydrogel probably the most useful material for tissue engineering and drug delivery.”
Inaugural CZ Biohub Chicago conference brings together scientists
In late 2024, top scientists involved with CZ Biohub Chicago gathered to share insights on next-generation sequencing, imaging, and bioengineering technologies at the initiative’s inaugural conference.
As a speaker at the conference, Prof. Savas Tay underscored the importance of spatial biology. While understanding what happens within a cell is important, it doesn’t not take into account the three-dimensional network of cells in the area. To understand that network, scientists are using new tools to create 3D maps of tissue.
“Everybody is interested in spatial biology,” said Savas Tay, a CZ Biohub Chicago Investigator who has received grants from the initiative. “When we rely on dissociated cells, we are losing a lot of information and context.”
Understanding a protein that stymies an immune response to viruses
Most interferons — proteins that send signals throughout the immune system — are beneficial when it comes to helping the body fight a virus. But interferon lambda 4 (IFNλ4) does the opposite; it makes an immune response worse. Studies have shown that people with the gene for IFNλ4 are less effective at fighting hepatitis C and can be more susceptible to COVID-19 and other respiratory viruses.
In research published in Nature Communications, Prof. Juan Mendoza developed a new method of producing and isolating IFNλ4. That enabled him and his team to determine the structure of the protein for the first time, revealing an unusual, floppy region of the protein. This unstructured region contributes to why IFNλ4 has been hard to make in cells. Now, future studies can probe whether modifying that region could minimize the negative impact of IFNλ4 on the immune response.
“This protein is one of the strongest genetic predictors of viral susceptibility, and it impacts a number of diseases,” Mendoza said. “We can now start to actually understand why that is.”
New platform to understand gene expression at the tissue level
Within the past five years, a new method called spatial transcriptomics enabled the analysis of gene expression in space using thin slices from intact tissues. This technology can provide a molecular map of a sample, allowing researchers to better understand tissue function and malfunction. But commercially available spatial transcriptomics technology is expensive, and it can only analyze small tissue samples.
To understand gene expression across larger tissues, Assoc. Prof. Nicolas Chevrier and his team created their own spatial transcriptomics platform by combining next-generation sequencing technology with an older technology: microarrays, which they outfitted with custom-designed probes.
The design, dubbed “Array-seq” and published in Nature Methods, can analyze tissue samples as big as nearly 12 square centimeters at a cost that is 50 times cheaper than commercially available systems.
“My hope is that anyone who needs spatial transcriptomics will find this technique useful for higher-throughput and less-expensive research,” Chevrier said. “This could help democratize and enhance the reach of spatiomolecular profiling.”
Klebsiella pneumoniae are common bacteria found in people’s intestines, but when they escape to other parts of the body, they can cause severe infections. K. pneumoniae are often spread within hospital settings, and drug-resistant strains have become common.
A team led by Asst. Prof. Mark Mimee developed a new strategy to fight these infections that involves collections of bacteriophages, viruses that naturally attack bacteria.
In research published in Cell Host & Microbe, the team showed that a mixture of these phages can successfully treat antibiotic-resistant Klebsiella pneumoniae infections in mice. To find the best combination, team identified several dozen phages with the capability of killing at least some Klebsiella strains, then analyzed what genetic factors in the bacteria made them most prone to being killed or weakened by each of those phages. They then developed a mixture of five phages that each targeted different components of the bacteria.
“In my clinic, I see patients with recurrent urinary tract infections caused by Klebsiella,” says urogynecologist Sandra Valaitis, MD, of UChicago Medicine, a co-author of the research. “Often these bacterial strains develop resistance to oral antibiotics, leaving patients with fewer options to clear the infection. We urgently need new ways of treating these bacteria.”
