DNA nanostructures as probes for multi-omic analyses
Lead Research Organisation:
University of Edinburgh
Department Name: Sch of Molecular. Genetics & Pop Health
Abstract
Background
Multi-omic analyses1 are expected to revolutionize medicine by increasing our understanding of disease and enabling treatments to be personalized. In multi-omic studies, experimental data is obtained using various high-throughput methods that probe a wide range of biomarkers. However, in many cases, different techniques must be used for each type of marker to be monitored. The apparatus required is often expensive and the procedures can be complex. The goal of this project is to create a low-cost easy-to-use platform that will allow many different biomarkers to be investigated in parallel in a single measurement.
In this system, DNA nanostructures will be used as customized molecular barcodes2,3. Synthetic DNA molecules will be designed to self-assemble4,5 into nanoscale objects, and a combinatorial set of such structures will be formed. Through chemical or biological modification of specific DNA molecules, each species of nanostructure will be designed to interact with one particular target. An assay will be established for the study of complex samples and streamlined quantitative methods will be developed for processing the large datasets that will be generated.
The technology resulting from this project has potential applications in various areas of medicine. It could be used to enhance our understanding of the causes and mechanisms of disease or it could be employed for microbial genotyping/phenotyping that would enable more targeted use of antimicrobials, contributing to ongoing efforts to combat antimicrobial resistance.
This project involves collaboration with Prof. Björn Högberg and his research group in the Department of Medical Biochemistry and Biophysics at the Karolinska Institute in Sweden. The Högberg lab develops new DNA-based methods and molecular tools for cell biology research.
The student will spend most of the PhD working in the Institute for Bioengineering in the School of Engineering at the University of Edinburgh, with visits to the Karolinska Institute as appropriate, and will receive input from Prof. Högberg and his research group.
Aims
The aim of this project is to develop the foundations of a new technology that has the potential to enable different omic datasets to be acquired simultaneously on complex samples in either a laboratory or a clinical setting.
Training outcomes
During this project, Suzanne will:
-become familiar with biological laboratory techniques
-learn to generate, curate and analyse large datasets
-master techniques for quantitative data analysis
-acquire experience in the development of a new technology for precision medicine
References
1. Multi-omics approaches to disease. Hasin, Seldin & Lusis. Genome Biology (2017) DOI: 10.1186/s13059-017-1215-1
2. Digitally encoded DNA nanostructures for multiplexed, single-molecule protein sensing with nanopores. Bell & Keyser. Nature Nanotechnology (2016) DOI: 10.1038/NNANO.2016.50
3. DNA-barcoded labeling probes for highly multiplexed Exchange-PAINT imaging. Agasti et al. Chemical Science (2017) DOI: 10.1039/c6sc05420j
4. Guiding the folding pathway of DNA origami. Dunn et al. Nature (2015) DOI: 10.1038/nature14860
5. DNA rendering of polyhedral meshes at the nanoscale. Benson et al. Nature (2015). DOI : 10.1038/nature14586
Multi-omic analyses1 are expected to revolutionize medicine by increasing our understanding of disease and enabling treatments to be personalized. In multi-omic studies, experimental data is obtained using various high-throughput methods that probe a wide range of biomarkers. However, in many cases, different techniques must be used for each type of marker to be monitored. The apparatus required is often expensive and the procedures can be complex. The goal of this project is to create a low-cost easy-to-use platform that will allow many different biomarkers to be investigated in parallel in a single measurement.
In this system, DNA nanostructures will be used as customized molecular barcodes2,3. Synthetic DNA molecules will be designed to self-assemble4,5 into nanoscale objects, and a combinatorial set of such structures will be formed. Through chemical or biological modification of specific DNA molecules, each species of nanostructure will be designed to interact with one particular target. An assay will be established for the study of complex samples and streamlined quantitative methods will be developed for processing the large datasets that will be generated.
The technology resulting from this project has potential applications in various areas of medicine. It could be used to enhance our understanding of the causes and mechanisms of disease or it could be employed for microbial genotyping/phenotyping that would enable more targeted use of antimicrobials, contributing to ongoing efforts to combat antimicrobial resistance.
This project involves collaboration with Prof. Björn Högberg and his research group in the Department of Medical Biochemistry and Biophysics at the Karolinska Institute in Sweden. The Högberg lab develops new DNA-based methods and molecular tools for cell biology research.
The student will spend most of the PhD working in the Institute for Bioengineering in the School of Engineering at the University of Edinburgh, with visits to the Karolinska Institute as appropriate, and will receive input from Prof. Högberg and his research group.
Aims
The aim of this project is to develop the foundations of a new technology that has the potential to enable different omic datasets to be acquired simultaneously on complex samples in either a laboratory or a clinical setting.
Training outcomes
During this project, Suzanne will:
-become familiar with biological laboratory techniques
-learn to generate, curate and analyse large datasets
-master techniques for quantitative data analysis
-acquire experience in the development of a new technology for precision medicine
References
1. Multi-omics approaches to disease. Hasin, Seldin & Lusis. Genome Biology (2017) DOI: 10.1186/s13059-017-1215-1
2. Digitally encoded DNA nanostructures for multiplexed, single-molecule protein sensing with nanopores. Bell & Keyser. Nature Nanotechnology (2016) DOI: 10.1038/NNANO.2016.50
3. DNA-barcoded labeling probes for highly multiplexed Exchange-PAINT imaging. Agasti et al. Chemical Science (2017) DOI: 10.1039/c6sc05420j
4. Guiding the folding pathway of DNA origami. Dunn et al. Nature (2015) DOI: 10.1038/nature14860
5. DNA rendering of polyhedral meshes at the nanoscale. Benson et al. Nature (2015). DOI : 10.1038/nature14586
Organisations
People |
ORCID iD |
| Katherine Dunn (Primary Supervisor) | |
| Suzanne Drennan (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| MR/N013166/1 | 01/10/2016 | 30/09/2025 | |||
| 2104508 | Studentship | MR/N013166/1 | 01/09/2018 | 31/08/2022 | Suzanne Drennan |