Ultra-sensitive protein detection by geometry-coupled amplification and kinetic proofreading
Name of applicant
Minke Nijenhuis
Title
Postdoctoral Fellow
Institution
Harvard University, Wyss Institute for Biologically Inspired Engineering
Amount
DKK 1,020,000
Year
2023
Type of grant
Internationalisation Fellowships
What?
Many pathogenic agents bear proteins in specific arrangements. For example, the icosahedral symmetry of viral capsids and the stacked architecture of amyloid fibrils in Alzheimer's disease. Minute amounts of these protein patterns influence disease progression from the early stages of pathogenesis. We aim to develop an ultra-sensitive detection methodology for pathogen-associated protein patterns.
Why?
Pathology is often caused beyond the genetic level and proteins are, therefore, the best markers for assessing immediate health. However, the ultra-sensitive detection of proteins remains a great analytical challenge because proteins cannot be easily amplified. Moreover, the state-of-the-art methodology does not recognize spatial protein arrangements, despite their importance in pathogenesis.
How?
Create finite-lifetime bifunctional nanostructures that (1) recognize pathogenic protein patterns and (2) amplify this signal via the rapid growth of sub-millimeter DNA-based ribbons, based on a geometric coupling of the recognition and amplification moieties. Between (1) and (2), the nanostructures are filtered through kinetic proofreading to ensure that only true records are amplified.