Designing a functional 3D scaffold for cancer early detection
Lead Research Organisation:
University of Manchester
Department Name: Materials
Abstract
Background & aim:
Cancer early detection (CED) is key to patient survival. One of the main challenges for such early detection it the molecular target. In this context in the past few years, it has been shown that many small non-coding miRNAs are dysregulated during the early stages of cancer, well before the manifestation of any cancer-related clinical symptom. This property combined with the non-invasive nature of miRNAs collection from patients' plasma and serum makes them ideal diagnostic indicators for CED. Current miRNAs detection approaches suffer from insufficient reproducibility, low accuracy, and poor sensitivity. To meet these challenges, we aim through this project to develop a new diagnostic platform using functional 3D peptide hydrogels for sequence-specific, PCR-free, fluorescent detection of miRNAs in a "one-pot" assay. Through this PhD project we will test the suitability of our novel hydrogel-based technology for rapid, robust and reliable screening of the unique miRNA fingerprint of lung cancer.
Objectives & Methodology:
Obj 1: Design and characterization of hydrogel for miRNA capture.
The student will investigate a range of peptide-based hydrogel with varying properties in particular electrostatic to investigate and understand the diffusion pathway of miRNA into the hydrogels. This will allow to design and hydrogel that is capable of capturing miRNA from complex biological fluids.
Obj 2: Synthesis of functional hydrogel with oligonucleotide split probe
A split probe fluorescent sensing approach will be used. First the oligonucleotide DABCIL probe will be conjugated to the base peptide in order to functionalize the hydrogel selected through Obj1. Subsequently the sensing hydrogels will be formulated with the two split probes and target miRNA will be used to perform proof of concept work and show that miRNA can indeed be detected with high sensitivity.
Obj 3: Use of cancer cell for proof-of-concept on new miRNA detection.
Cancer cell lines will be used to demonstrate the ability of the hydrogel to detect miRNA directly from conditioned media. For this purpose a generic miRNA will be selected that is released in all cancer as well as two specific miRNA to the two cancer cell lines selected.
Cancer early detection (CED) is key to patient survival. One of the main challenges for such early detection it the molecular target. In this context in the past few years, it has been shown that many small non-coding miRNAs are dysregulated during the early stages of cancer, well before the manifestation of any cancer-related clinical symptom. This property combined with the non-invasive nature of miRNAs collection from patients' plasma and serum makes them ideal diagnostic indicators for CED. Current miRNAs detection approaches suffer from insufficient reproducibility, low accuracy, and poor sensitivity. To meet these challenges, we aim through this project to develop a new diagnostic platform using functional 3D peptide hydrogels for sequence-specific, PCR-free, fluorescent detection of miRNAs in a "one-pot" assay. Through this PhD project we will test the suitability of our novel hydrogel-based technology for rapid, robust and reliable screening of the unique miRNA fingerprint of lung cancer.
Objectives & Methodology:
Obj 1: Design and characterization of hydrogel for miRNA capture.
The student will investigate a range of peptide-based hydrogel with varying properties in particular electrostatic to investigate and understand the diffusion pathway of miRNA into the hydrogels. This will allow to design and hydrogel that is capable of capturing miRNA from complex biological fluids.
Obj 2: Synthesis of functional hydrogel with oligonucleotide split probe
A split probe fluorescent sensing approach will be used. First the oligonucleotide DABCIL probe will be conjugated to the base peptide in order to functionalize the hydrogel selected through Obj1. Subsequently the sensing hydrogels will be formulated with the two split probes and target miRNA will be used to perform proof of concept work and show that miRNA can indeed be detected with high sensitivity.
Obj 3: Use of cancer cell for proof-of-concept on new miRNA detection.
Cancer cell lines will be used to demonstrate the ability of the hydrogel to detect miRNA directly from conditioned media. For this purpose a generic miRNA will be selected that is released in all cancer as well as two specific miRNA to the two cancer cell lines selected.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/R513131/1 | 01/10/2018 | 30/09/2023 | |||
| 2509619 | Studentship | EP/R513131/1 | 01/10/2020 | 31/03/2024 | Niall Mahon |
| EP/T517823/1 | 01/10/2020 | 30/09/2025 | |||
| 2509619 | Studentship | EP/T517823/1 | 01/10/2020 | 31/03/2024 | Niall Mahon |