16 UChicago Researchers Awarded $7.2 Million from Chan Zuckerberg Biohub Chicago
The Chan Zuckerberg Biohub Chicago announced its first cohort of Investigators, 48 innovative scientists and engineers from the Biohub’s three partner universities, Northwestern University, University of Illinois Urbana-Champaign, and University of Chicago. (Image courtesy Chan Zuckerberg Biohub Chicago)
The Chan Zuckerberg Biohub Chicago has funded its first cohort of Investigators at its partner institutions – including 16 researchers from the University of Chicago.
The funding – a total of $7.2 million for nine projects led by UChicago investigators – will enable the researchers to perform “high-risk, high-reward work” across topics related to instrumented tissues and research linked to inflammation and the functions of the immune system.
“The new Investigators from UChicago and our other two partner institutions embody the Biohub’s core value of focusing on high-risk, high-reward interdisciplinary collaboration. These incredible teams will pursue big research questions that couldn’t be done anywhere else, and we’re excited to see the scientific progress they will make,” said Shana Kelley, President of the CZ Biohub Chicago.
Investigators will attend Quarterly Investigator Meetings, which provide opportunities to build collaborative efforts between partner universities and Biohub scientists and engineers, present progress from ongoing work, and interact with external speakers.
Funded Projects:
// High-resolution mapping of mRNA biogenesis kinetic during early response to immune stimuli
Luis Barreiro, professor of medicine, and Yang Li, associate professor of medicine and human genetics, have been awarded funding over three years to investigate mRNA biogenesis and develop high-resolution temporal maps of early response to infection.
“We are studying variation in immune responses across people,” explained Barreiro, whose labs is specifically interested in understanding the role that natural selection has played in human susceptibility to disease.
“If I take my cells and yours, and expose them to a pathogen, why is it that our cells respond so differently?” he asks. Knowing the answer would have myriad implications in disease prevention, treatment, and outcomes.
“If you know how genetics impact the response to a pathogen, and ultimately susceptibility to disease, we may be able to identify biomarkers to use in the context of personalized medicine,” Barreiro added.
For the Biohub project, Barreiro and Li will closely examine and measure mRNA transcription rates during early infection using an iPSC-induced macrophage system. This will enable them to understand how immune cells can effectively respond to infection without causing chronic inflammation. Both labs use cutting-edge genomic techniques and innovative technologies, including computational tools, among other approaches.
// ATF Mapping Dynamic RNA-Protein Interactions in Inflammation: From Cells to Animals to Patients
Bryan Dickinson, professor of chemistry, and Benjamin Shogan, associate professor of surgery, have been awarded funding to support groundbreaking research on dynamic protein-RNA interactions (PRIs) that fine-tune inflammation.
This award will enable the team to expand its innovative work on BAP-seq, a chemical biology technology designed to measure RNA localization and interactions in living systems.
“Our team will leverage and expand BAP-seq to uncover novel, dynamic PRIs that modulate inflammation in cellular assays, animal models, and eventually, human patients,” said Dickinson. This research focuses on surgical tissue healing, addressing a critical unmet medical need caused by dysregulated inflammatory responses.
The grant will fund sequencing experiments and technological development of BAP-seq in the Dickinson group and the use of these technologies to further understand intestinal healing of gastrointestinal surgery in the Shogan group.
The project aims to “develop a deep understanding of how inflammatory regulation is necessary for intestinal healing and how disturbances of inflammation lead to postoperative complications,” said Shogan.
// Measurement of Inflammatory Responses
An interdisciplinary team led by Pritzker School of Molecular Engineering immunoengineering Professor Aaron Esser-Kahn, quantum researcher Assistant Professor Peter Maurer, and Professor of Medicine Alexander Pearson, will receive funding over three years to develop quantum-enabled identifiers (Q-IDs) that will allow for the investigation of individual immune cells in real-time.
“It’s a project that would not yet be funded by a larger agency but has the potential to revolutionize the way we study and monitor biological phenomena,” Esser-Kahn said.
“Our approach relies on nanodiamonds containing nitrogen-vacancy (NV) centers as photostable fluorophores, which are arranged in unique bar codes using DNA origami,” Maurer said. “Eventually these Q-IDs will be able to monitor thousands of immune cells, which will provide insights into inflammation in tumors and tissues and potentially lead to new therapies for chronic inflammation and cancer.”
“The Biohub has created a unique opportunity to team researchers from diverse scientific backgrounds and develop creative approaches for high-impact, cutting-edge challenges,” Pearson said.
// Data-driven pipelines to learn and engineer spatiotemporal patterning in endothelial inflammation
Horace B. Horton Professor of Physics, Molecular Genetics, and Cell Biology Margaret Gardel, and Professor of Physics Vincenzo Vitelli, will receive funding over three years to explore new approaches to characterize inflammatory response at the cell and tissue scale. Both are members of the James Franck Institute and Center for Living Systems.
“The flexibility of the award provides the freedom for us to develop techniques and ideas, a kind of risk not offered with traditional funding approaches,” Gardel said. “Moreover, the CZ Biohub Investigator program is an exceptional opportunity for building the biomedical and bioengineering community across Chicagoland that will impact our research and training.”
The flexibility of the award also offers the freedom to develop techniques and ideas that are typically considered too risky for traditional funding sources.
Vincenzo Vitelli added that the grant will facilitate the development of novel machine-learning techniques aimed at inferring interpretable mathematical models of inflammatory response directly from data. “This is somewhat the other way around compared to classic modeling approaches in which one starts with clear hypotheses and compares predictions with data only at the end of the process,” explained Vitelli.
// AI-Driven Prediction and Design of TCR-Peptide Interactions for Inflammation Studies
Assistant Professor of Family Medicine and Pathology, Aly Khan, will receive funding over three years to better understand how immune cells interact with pathogens using novel machine learning techniques.
“We are leveraging recent advances in AI and machine learning to better model, predict, and understand T cell-antigen interactions,” explained Khan.
Adult humans have approximately 10^11 T cells, which function as “living sensors” and play a pivotal role in mediating immune responses and inflammation in health and disease. However, a critical question remains: Which antigens are these T cells sensing to initiate immune and inflammatory processes? The central objective of the CZ Biohub award is to explore this fundamental question in immunology, noted Khan.
The project builds on research recently published in Science about modeling protein-protein interactions. This earlier work addressed the general challenge of bridging experimental methods for screening protein interactions with protein language models.
“These models are similar to Large Language Models like GPT-4 but are specialized for studying the ‘language’ of proteins. We view TCR-antigen interactions as a specialized version of this general protein interaction problem,” Khan explained. “Our current focus is on harnessing unique aspects of validated immune system biology to better guide the design of our methods for the specific task of modeling TCR-antigen interactions.”
// Expanding the Fluorescent Labeling Palette for Multiplexed Imaging and Sensing of Biomolecules from Tissue
Allison Squires, Neubauer Family Assistant Professor of Molecular Engineering and Samantha Riesenfeld, assistant professor of molecular engineering and medicine, both at PME, will receive funding over three years.
The goal is to build an interdisciplinary platform that integrates new multiplexing technologies from the Squires Lab with the Riesenfeld Lab’s computational modeling capabilities.
“We’re working to push the boundaries of both what we can measure from a minimum amount of sample input, and what we can learn about inflammatory processes from these new data streams,” Riesenfeld said.
The research is aimed at new ways of detecting and understanding inflammatory biomarkers. The team will initially target a type of gut immune cell called intestinal intraepithelial lymphocytes, which if activated can lead to inflammation and tissue destruction in Celiac disease and inflammatory bowel disease and promote some forms of cancer.
“CZ Biohub Chicago’s mission is to support ambitious, high-impact projects that might be too risky for traditional funding mechanisms,” Squires said. “But beyond funding, the Biohub is bringing together bioengineers from across the region and challenging them to coordinate their efforts to develop entirely new, integrated systems for both biomedical applications and fundamental discovery that are bigger and different from what traditional teams of collaborators could accomplish.”
// Probing spatiotemporal dynamics of tumor immunity with a high-throughput model system
Melody Swartz, William B. Ogden Professor of Molecular Engineering and Vice Dean for Faculty Affairs at the PME, will receive funding over three years for immunology research.
Swartz, who also holds a joint appointment with the Ben May Department for Cancer Research, works in both basic hypothesis-driven research as well as in translational applications.
Her research focuses on elucidating and exploiting the roles of lymphatic function as it relates to cancer and chronic inflammatory diseases including asthma, using a variety of interdisciplinary approaches from bioengineering, immunobiology, physiology, cell biology, and biomechanics.
// Spatially resolved proteomic characterization and computational modeling of lymphoid tissues during B cell differentiation
PME Professor Savas Tay, who is also a member of UChicago’s Institute for Genomics and Systems Biology, and UChicago Medicine Professor Marcus Clark will receive funding over three years to develop a new technology that measures biological molecules like proteins and mRNA from tissues in a three-dimensionally resolved manner. They will use this to understand the development of B-cells, a type of white blood cell that makes antibodies.
“We can better characterize immune tissues with this technology, which will lead to a better understanding of dynamics events during immune response as well as developing computational models of these events,” Tay said.
// Inflammation-free, hydrogel-based 3D bioelectronics for tissue-embedded tracking of inflammation
PME Assistant Professor Sihong Wang will receive funding over three years to develop a new type of 3D bioelectronics technology that can be used to record and modulate inflammation activities.
“The success of this project will provide a new type of tools for the study of real-time and longitudinal study of biological processes in live tissue models and animal models,” Wang said.
“Unprecedentedly, the tool will be able to interface with tissue models in a 3D-embedded manner, which can achieve the recording and modulation functions with spatial heterogeneity and high density. Such capabilities can enable the acquisition of a much deeper understanding of biological processes such as inflammation.”
CZ Biohub Chicago is 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.
CZ Biohub Chicago is part of the CZ Biohub Network, a group of nonprofit research institutes created and supported by the Chan Zuckerberg Initiative. The institute was created as a close collaboration between the University of Chicago, University of Illinois Urbana-Champaign, and Northwestern University.