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Targeting miR-29 in cutaneous wounds


Faculty of Biology, Medicine and Health

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Dr S Kurinna Applications accepted all year round

About the Project

The development of efficient strategies for the improvement of wound repair requires understanding of the mechanisms underlying normal and impaired healing. Many factors can interfere with one or more phases of the cutaneous healing process, thus causing impaired wound healing in patients. Recent data implicates microRNAs as one such factor involved in wound repair [1]. Because of the short sequence (~20 nt) and the tissue-specific activity, miRs may be targets for oligonucleotide-based RNA silencing therapy [2]. This approach is particularly promising in skin due to accessibility of this tissue for local miR manipulation. However, functions of miRs in homeostatic and regenerating epidermis remain largely unknown. Our previous work identified an important function of miR-29s in regulating desmosomes in normal and hyperproliferative epidermis [3]. For the proposed project, we will perform a tandem pull-down of miR-29 target RNA in human keratinocytes under quiescent and proliferating conditions. Thus, we will identify new miR-29 targets regulating growth and differentiation of keratinocytes and select RNAs coding for potential promoters of wound healing. Finally, we will apply layer-by-layer wound dressing technology to deliver miR-29 anti-sense oligonucleotides (ASO) at different stages of wound healing in vivo. The project will identify novel approaches and mechanisms to improve cutaneous wound repair. It will determine how manipulating of the miR-29 function could be used to improve wound healing in vivo, and will identify RNA targets of miR-29, which themselves could be used for wound therapy. In addition, it will open new avenues for the use of miR-based therapy for other types of cells in regenerative medicine (e.g., hepatocytes, neuroblasts, and muscle stem cells).

Training/techniques to be provided:
The mRNA and miRNA analyses will be carried over in Dr. Kurinna lab, where the candidate will also learn cloning of 3’UTRs into dual-Glo reporter vectors, luciferase assays, and mammalian tissue culture technics. The training will include high-resolution microscopy (core facilities, UoM), quantitative PCR, and protein analysis. PhD candidate will be presenting and discussing results of experiments at joint group meetings and local conferences in the form of oral and poster presentations. At the end of the project, the candidate is strongly encouraged to write a short research paper and submit it to a relevant peer-reviewed journal.

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in molecular biology and tissue culture are encouraged to apply.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (https://www.bmh.manchester.ac.uk/study/research/fees/). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/).

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

Banerjee J, Sen CK: MicroRNAs in skin and wound healing. Methods Mol Biol 2013, 936:343-356.
2. Opalinska J: Nucleic acid drugs in the clinic. Expert Opin Drug Discov 2007, 2:321-333.
3. Kurinna S, Schafer M, Ostano P, Karouzakis E, Chiorino G, Bloch W, Bachmann A, Gay S, Garrod D, Lefort K, et al: A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes. Nat Commun 2014, 5:5099.
4. Almquist BD, Castleberry SA, Sun JB, Lu AY, Hammond PT: Combination Growth Factor Therapy via Electrostatically Assembled Wound Dressings Improves Diabetic Ulcer Healing In Vivo. Adv Healthc Mater 2015.
5. Imig J, Brunschweiger A, Brummer A, Guennewig B, Mittal N, Kishore S, Tsikrika P, Gerber AP, Zavolan M, Hall J: miR-CLIP capture of a miRNA targetome uncovers a lincRNA H19-miR-106a interaction. Nat Chem Biol 2015, 11:107-114.
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