CAREER: Elucidating structure-function relationships of inflammasome-activating nanomaterials

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). NON-TECHNICAL ABSTRACT:

This CAREER award proposes to develop polymeric nanomaterials and investigate their effects on immune cell functions, specifically, activation of the inflammasome, a multiprotein complex that controls immune cell functions during normal and pathological (leading to disease) processes. By varying the self-assembly of their polymeric building blocks, the proposed set of nanomaterials will activate different inflammasome functions, and will be used as tools to evaluate how their surface and core chemical patterns influence uptake, intracellular fate, and inflammasome activation in immune cells.

The results from the proposed studies will generate a set of new guidelines that will provide clear criteria for the design of novel nanomaterials that elicit predictable degrees of inflammasome activation and can be used for biological applications, including immunotherapy and vaccines. The project’s educational goals are to integrate the proposed research modules into several educational programs developed for students at various educational levels spanning the K-12, college, and graduate levels and increase the participation of students from underrepresented groups in bioengineering research.

These efforts include the integration of mentorship and research experiences into immuno-engineering and bioengineering courses to provide a unique learning experience to a diverse workforce at the emerging interface of chemical engineering, biomaterials, and immunology, a summer workshop for local K-12 students from underrepresented groups, new research experiences for women and underrepresented students to encourage and promote the involvement of these students in the field of bioengineering, recruiting graduate students from underrepresented groups and an online open course network of teachers and students interested in immunoengineering to disseminate, discuss, and collaborate.

TECHNICAL ABSTRACT:

The goals of this CAREER proposal are to establish strong and integrated research and educational program that: (1) provides a foundational understanding of how different nanomaterials interact with immune cells resulting in inflammasome activation, (2) advances the field of inflammasome-activating nanomaterials for biological applications including targeting inflammatory diseases and (3) encourages and inspires a diverse set of K-12 students, undergraduate and graduate students to participate in learning and contributing to the bioengineering field. This proposal will develop a library of polymeric supramolecular nanoparticles with different surface and core properties to elucidate the effects of nanomaterial properties on inflammasome activation and identify the underlying molecular mechanisms.

Specifically, supramolecular polymeric nanomaterials with tunable surface and core properties will be developed to determine how they influence uptake, intracellular fate, and inflammasome activation in various immune cells. The mechanisms underlying inflammasome activation in response to various nanomaterials will be dissected by assessing key components of lysosomal disruption–cathepsin B maturation and calcium influx-mitochondrial dysfunction pathways.

The PI’s long-term educational goal is to mentor and train the diverse cadre of students from pre-college (K-12), undergraduate and graduate levels as the next generation of bioengineers to become critical thinkers capable of contributing to society and the growing body of scientific knowledge either through academic, industrial or entrepreneurial route. Towards that goal, the educational aims for this project include: (1) integration of mentorship and research experiences into the educational curriculum, including project-based biology for engineers course and a lab-based immunoengineering course; (2) to encourage and promote the involvement of K-12 students from underrepresented groups in the bioengineering field by leveraging current efforts in organizing summer workshops that provide hands-on training and graduate students run ‘Science Day’ that will include various activities such as students presentations, science trivia and team-based competition; (3) designing and developing an online resource for sharing immunoengineering course materials to instructors and graduate students. (4) to increase awareness about how engineers can contribute to the biology and immunology field to advance human health by disseminating outcomes of our research to broader communities, including the research community and the general population.

The proposed research will generate a set of new guidelines that will provide clear criteria for structural and functional requirements to design the next generation of novel nanomaterials that elicit predictable degrees of inflammasome activation and can be used for various biological applications.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.