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(BBSRC DTP CASE) Fostering the next generation of molecular diagnostics: 3D microfluidic RNA-sensing hydrogel biosensors for clinical analysis of miRNA biomarkers.


Project Description

This project will be carried out at the interface between academia and industry, in close collaboration with our industrial partner, Manchester BIOGEL Ltd, to facilitate translational development of a novel diagnostic platform by bridging the gap between a scientific discovery and its future commercialisation.

This multidisciplinary research will be focused on the design and fabrication of novel 3D microfluidic RNA-sensing biosensors using self-assembling peptide hydrogel, capable of recognising and detecting pathogenic microRNA sequences, which play a functional role in development of many diseases in humans1-4, including Alzheimer’s and Parkinson’s diseases 1, cardiovascular2 and autoimmune3 diseases, as well as various types of cancers.4 Rapid detection of microRNA biomarkers offers the advantage of early disease diagnosis and improved therapeutic treatment. Thus, new technological advances for fast, robust and reliable screening for such diseases may facilitate effective therapeutic interventions with fewer side effects, leading to improved patient health and quality of life.

The aim of this project is to develop a next generation of molecular diagnostics by fabricating the 3D RNA-sensing microfluidic devices for detection of disease-relevant miRNA biomarkers in biological and clinical samples. This new diagnostic platform will be based on our recently developed self-assembling peptidyl-oligonucleotide hydrogel 5 with chemically incorporated oligonucleotide recognition motif to ‘fish out’ and sense specific microRNA sequences from biological samples, thus allowing fluorescent signal generation. The controlled assembly of individual molecules into desired nano-architectures will be precisely engineered by manipulating the chemical structure of the nano-molecular building blocks to trigger fluorescence signal on binding with microRNAs, which are linked to human pathophysiology.

The training will be provided at the interface between chemical and structural biology, material sciences, peptide chemistry, nanotechnology, biopolymer chemistry and architecture. The recruited student will benefit from established collaborations between the academic groups to develop research expertise across these disciplines. Industrial placement at Manchester BIOGEL Ltd will provide the recruited student with invaluable experience of the commercialisation process and expose him/her to the intense industrial environment of the SME business with strict commitments to project delivery and budgetary targets. This will encourage the recruited student to appreciate and value collaborative and coordinated multidisciplinary approaches necessary to resolve healthcare grand challenges. Given the breadth, depth and scope of skills provided, such training would support progression into a variety of career positions within academic and/or industrial settings. Graduates with skills-sets spanning these areas are rare, so the training would provide a solid platform for career development.

http://www.pharmacy.manchester.ac.uk/staff/ElenaBichenkova/
https://www.research.manchester.ac.uk/portal/a.saiani.html
https://www.research.manchester.ac.uk/portal/harmesh.aojula.html
https://manchesterbiogel.com/

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the BBSRC DTP websitewww.manchester.ac.uk/bbsrcdtpstudentships

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. Nelson P.T., Wang W-X. and Rajeev B.W. ‘MicroRNAs (miRNAs) in neurodegenerative diseases.’ Brain Pathol. (2008) 18, 130-138.

2. Ono K., Kuwabara Y. and Han J. ’MicroRNAs and cardiovascular diseases.’ FEBS (2011) 278, 1619-1633.

3. Qu Z., Li W. and Fu B. ‘MicroRNAs in Autoimmune Diseases.’ BioMed Res. Int. (2014) 2014. 527895.

4. Tahiri A., Leivonen S.K., Lüders T., Steinfeld I., Ragle Aure M., Geisler J., Mäkelä R., Nord S., Riis M.L., Yakhini Z., Kleivi Sahlberg K., Børresen-Dale A.L., Perälä M., Bukholm I.R., Kristensen V.N. ‘Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors.’ Carcinogenesis (2014) 35, 76-85.

5. King P.J., Saiani A.., Bichenkova E.V. and Miller A.F. ‘A de novo self-assembling peptide hydrogel biosensor with covalently immobilised DNA-recognising motifs.’ Chem Commun (Camb). (2016) 52, 6697-700.

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