R&D Engineer Emily Huynh of CZ Biohub San Francisco's Bioengineering team works on circuits in the lab. Credit: Barbara Ries
Inflammation plays a key role in many diseases, including cancer, heart disease and Alzheimer’s disease. It is also implicated in organ failure and severe infectious diseases, such as SARS-CoV-2. However, despite advancements in single cell imaging and animal models, inflammation remains a difficult thing to study. Researchers can’t study it in a petri dish, and looking at it in mice and other lab animals is not always scalable to humans.
That’s one of many reasons why inflammation will be the focus of the newly announced Chan Zuckerberg Biohub Chicago. Created by husband and wife duo Mark Zuckerberg and Priscilla Chan, who is a pediatrician, the Chan Zuckerberg Initiative was founded in 2015 to help solve some of society’s toughest challenges. One year later, they launched the first CZ Biohub in San Francisco, which brings together talent from Stanford University, the University of California San Francisco and the University of California Berkeley to pursue grand scientific challenges related to cell biology and infectious disease/
And now, the second CZ Biohub in Chicago will focus on engineering technologies to make precise, molecular-level measurements of biological processes within human tissues, with an ultimate goal of understanding and treating the inflammatory states that underlie many diseases. The Biohub brings together scientists and researchers from the University of Chicago, Northwestern University, and the University of Illinois Urbana-Champaign.
Shana Kelley, professor of chemistry and biomedical engineering at Northwestern, will lead CZ Biohub Chicago.
“If we can get to the causes of inflammation, the drivers of inflammation, if we can understand how to turn inflammation around, there’s just so many different disease states we can impact,” Kelley told Laboratory Equipment in a recent interview.
CZ Biohub Chicago projects will employ an engineering-driven approach to studying human biology. The first projects will focus on embedding thousands of sensors and sampling probes in human and engineered tissue to monitor molecular and cellular signals. With unprecedented resolution, the researchers are hoping to reveal how disruptions in these processes lead to inflammation and disease. This obtained data will be the first holistic and direct measurements of inflammation in human tissue.
This is unconstrained creativity…and that’s a great, great way to do science.
Shana Kelley
“It’s just not possible to get a handle on what happens in human tissues really comprehensively in a mouse,” said Kelley. “There are things that can be looked at but cell-cell communication, looking at tissues going from healthy to just starting to be inflamed to being chronically inflamed to being diseased—that’s really hard to do in the context of an animal. It’s easier to do in a system like we’re building that is highly engineered where we can have control over everything and can make very subtle changes.”
The Biohub researchers will be building a lot of their own instruments because “that’s the way engineers work.” Kelley said they will use microfabrication to build a lot of microfluidic and sensing devices, but will also employ different types of mass spectrometry systems for -omics measurements as well as existing spatial profiling systems. The data derived from analysis with proteomics and metabolomics will then be used to build really rich datasets.
While engineers are in high demand for Kelley’s projects, collaboration is the name of the game for the CZ Biohub network. Researchers in applied physics, chemistry, biology, mechanical, electrical and more will all eventually work on projects for the CZ Biohub Chicago. There are even less-traditional collaborations in the works. For example, Kelley said they are currently working with the head of dermatology at Northwestern because she has “incredible models of human skin.”
“It’s very valuable to be able to interact directly with those that understand what is happening in the clinic,” said Kelley. “We will not be limiting ourselves based on labels. It’s really just about building a very diverse team, people from many different backgrounds and disciplines. We’re trying to do things we’ve never done before—we’re not going to get there with just one particular kind of person.”
Collaboration and inspiration
When CZ Biohub San Francisco launched in 2016, building cell atlases at single-cell resolution was a major focus. This initiative has been incredibly successful, leading to the development of whole-organism cell atlases of mice, flies, lemurs, and—in the project known as the Tabula Sapiens—humans. The Tabula Sapiens work complements that of the international Human Cell Atlas effort, which aims to map and characterize all cell types in the healthy human body.
Kelley says she’s looking forward to her Chicago team building on the successes of San Francisco’s Biohub, with the potential for a lot of collaboration between the two Biohubs and all six universities. At the same time, Kelley stressed that the Chicago Biohub is its own entity, with a unique identity, unique focus and unique way of doing science.
“It’s an interesting thing to think about for those of us who have functioned our entire careers inside a university, it’s a different way of thinking,” said Kelley. “It’s a way of thinking where there are no boundaries. You don’t have to consider what department people are in, you don’t have to think about graduate studies or course requirements or renewing a grant. This is unconstrained creativity, not second-guessing your ideas because they won’t be fundable or you can’t get the paper out fast enough. It’s really just, what would be impactful to try, where is our intuition leading us—and that’s a great, great way to do science.”