EAGER: Engineered, Smart, Nucleic Acid-Binding, Intrinsically Disordered Proteins to Enable Ubiquitous Detection of Viral Pathogens and Diagnosis

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The past decade has seen the emergence of several epidemics of deadly viral diseases, most notably, COVID-19. A key front-line defense against the spread of these diseases is the ability to rapidly detect viruses in infected humans, and in other contexts. This project addresses the urgent need for fundamental research that enables promising new, high performance technologies for detection of specific viruses. Low cost, widely deployable new testing strategies for detection of viral ribonucleic acids (RNAs) can greatly enhance understanding and mitigation of the spread of epidemics and pandemics. This interdisciplinary research project provides opportunities to graduate and undergraduate students, including members of underrepresented groups, to develop research skills and to work across disciplines.This research explores novel approaches to significantly enhance key steps and the performance of bioanalytical methods that are alternatives to the time-consuming testing based on polymerase chain reaction amplification. In the first aim of this project, the research team capitalizes on the phase change behavior of genetically engineered, bioinspired, intrinsically disordered proteins (IDPs) to concentrate and enhance rapid, efficient viral RNA isolation. The second aim explores the potential use of IDP as chaperones to effectively catalyze RNA hybridization and strand displacement reactions. These reactions are central to viral nucleic acid detection methodologies such as CRISPR-Cas9 triggered strand displacement amplification, toehold switches, and molecular logic circuits. The goal of this project is to enable facile, massive deployment of low-cost, point-of-care virus detection and diagnosis.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.