High-Throughput Screening of Evolutionary Biological Materials
Abstract
The goal of this project is to establish the genetic basis of fiber forming protein structures via a pioneering high-throughput screening system based on transient thermal-reflectivity (TTR) spectroscopy. This novel method offers the first high-throughput screening tool that reports on the structural features of protein aggregation. Here, we propose to screen an ultra-large number (109) of potential fiber-forming genes. We will achieve the proposed goal by investigating three fundamental questions: (i) what is the underlying sequence-structure relationship for protein aggregation? (ii) what is the complete set of fiber-forming proteins, given that only few have been discovered up to date?; and (iii) how can we uncover new fiber-forming genes in bacterial targets? The proposed approach will generate fundamental knowledge about fiber-promoting genes. Recently, we discovered a new technique to screen protein sequences based ultrafast laser-probing spectroscopy, which has never been applied before in this research domain. Our novel TTR technique enables screening of 10^8-10^9 different structural polypeptide sequences for protein aggregates formation in hours, a feat that would be impossible to achieve with existing screening tools such as fluorescence, immunostaining, or functional assays. Successful development of this TTR-based screening approach for proteins will have a significant impact on multiple applications for DoD in various fields (e.g., materials science, agriculture, and medicine) and open new avenues of protein research.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 30, 2019
- Accession Number
- AD1075020
Entities
People
- Benjamin Allen
- Melik Demirel
Organizations
- Pennsylvania State University