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Function of miRNAs in formation and regeneration of human hair follicles


Project Description

Recent advances in treating a severe skin condition with autologous transgenic keratinocyte cultures emphasises the importance of molecular mechanisms in selecting subpopulations of skin cells for cutaneous repair [1]. At the same time, unbiased single-cell RNA sequencing discovers new stem cell compartments amongst the keratinocytes in mouse epidermis and in hair follicles (HF) [2]. Previous research and our preliminary data point to cell-type specific expression and functions of microRNA-29 family (miR-29s) in distinct populations of HF keratinocytes (Figure). Importantly, high levels of miR-29 in the inner root sheath cells (IRS) of HF are preceded by virtually undetectable levels of miR-29 in the basal and in the outer root sheath (ORS). Thus, miR-29s repress specific mRNAs at the point of early differentiation, allowing differentiation to proceed in a tightly controlled, cell-specific manner. The proposed project will aim at:
1) identification of specific mRNAs - targets of miR-29s in the ORS and IRS keratinocytes,
2) functional analysis of mRNA targets in tissue culture and in human HF ex vivo.
Our preliminary data suggests that miR-29 regulate the interactions between two specific layers of the IRS via cell-cell contact formation. We will also investigate a possibility of miRNA-regulated secretion of TGF-beta factors during the hair cycle. Overall, the results of this project will contribute to our understanding of translational regulation of normal cell differentiation in vivo, as well as growth and regeneration of human hair follicles.

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 http://www.internationalphd.manchester.ac.uk.

Funding Notes

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 or with an interest in organ mimi-culutres are encouraged to apply.

This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

Informal enquiries may be made directly to the primary supervisor.


References

1. Hirsch T, Rothoeft T, Teig N, Bauer JW, Pellegrini G, De Rosa L, Scaglione D, Reichelt J, Klausegger A, Kneisz D, et al: Regeneration of the entire human epidermis using transgenic stem cells. Nature 2017, 551:327-332.
2. Joost S, Zeisel A, Jacob T, Sun X, La Manno G, Lonnerberg P, Linnarsson S, Kasper M: Single-Cell Transcriptomics Reveals that Differentiation and Spatial Signatures Shape Epidermal and Hair Follicle Heterogeneity. Cell Syst 2016, 3:221-237 e229.

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