RPG Student List

 

Henson Lim LEE YU

Doctor Candidate in Chemical and Biomolecular Engineering

Supervisor: Prof. I Ming HSING

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Research Topic

Nucleic Acid-Enzyme Molecular Machines and its Applications

Abstract

Molecular Machines can be divided into three main parts: a sensor, processor, and an actuator. In the case of a nucleic acid-enzyme molecular machine, the sensor can be a DNA probe where it is able to detect a complementary strand via Watson-Crick base-pair hybridization or a functional DNA structure such as an aptamer or a DNAzyme that can detect a specific protein, ion, or other small molecules. The processor can be a set of enzymes that act on DNA such as nucleases, polymerases, and ligases. And the actuator can be any other molecule to translate the reaction that happens at the molecular level to an observable signal such as colorimetric, fluorescence, and an electrochemical signal. By carefully designing the nucleic acid sequence as sensor, and choosing the right set of enzymes, the possible applications are endless.

The most common application for DNA-based molecular machines are in the development of a biosensor. In this study, an ultrasensitive and selective detection platform for point-of-care diagnostics will be designed. An enzyme-based series of nucleic acid reactions will be developed to be able to detect very low quantities of the target analyte. Since this is a platform technology, this should theoretically work for various sequences, although the prototype will be based on Salmonella typhimurium, a major causative agent of food-borne illnesses. This is an ideal analyte as well to create a specific platform since more than 2500 serovars are known for Salmonella.

The technology can also be expanded to include applications on personalized medicine, where specific SNPs or gene sequence can be used to differentiate drug response, or in genome sequencing where the specific sequence is determined de novo. To the best of our knowledge, these proof-of-concept studies open up novel applications of nucleic acid-enzyme machines.

Journal Publication


Fan, Tsz Wing; Lee Yu, Henson Lim; Hsing, I-Ming, "Conditional Displacement Hybridization Assay for Multiple SNP Phasing", (2017)
 
Lee yu, Henson Lim; Zhang, yinghua; Hsing, I-ming, "Kinetically-Enhanced DNA Detection via Multiple-Pass Exonuclease III-aided Target Recycling", (2017)
 
Lee yu, Henson Lim; Zhang, Yinghua; Hsing, I-Ming, "Kinetically-enhanced DNA detection via multiple-pass exonuclease III-aided target recycling", (2017)
 
Lee yu, Henson Lim; Maslova, Anastasia; Hsing, I-Ming, "Rational Design of Electrochemical DNA Biosensors for Point-of-Care Applications", (2017)