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To address the functional significance of circadian clock genes in regulating the “stemness” and tumorigenesis of mammary cells


Project Description

Circadian (24 hourly) rhythms generated by our intrinsic biological clocks play critical roles in regulating physiology and behaviour. Cell autonomous circadian clocks are involved in governing cell division, differentiation, DNA damage repair and cell metabolism. Recent epidemiological studies have suggested links between disruption to circadian rhythms (for example women shift workers) and susceptibility to breast cancer. But the underlying molecular and cellular mechanisms are largely unknown.

In collaboration with the Streuli group, we have recently characterized the circadian clocks in mammary epithelial cells and stem cells. By time series microarrays, we have revealed several clock controlled pathways that have been previously implicated in stem cell function and in the development of breast cancer. This project aims to focus on a few of these key genes and pathways, in order to gain in depth understanding of the role of clock genes in the self-renewal, differentiation and malignant transformation of mammary stem cell.

In this project, we are going to use primary cell culture of mammary epithelial cells and stem cells from transgenic animals with clock gene mutations, mammosphere assays, immunocytochemistry, in vitro gene knockdown studies, real-time clock reporter techniques and lentiviral transduction to address the functional significance of circadian clock genes in regulating the “stemness” and tumorigenesis of mammary cells. This new knowledge will help understand the functional links between clock disruption and breast cancer risks.


Funding Notes

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

Janich P, Meng QJ, Benitah SA (2014). Circadian control of tissue homeostasis and adult stem cells. Curr Opin Cell Biol. 31:8-15.

Dudek M, Gossan N, Nan Yang N, Im H-J, Ruckshanthi JPD, Yoshitane H, Li X, Jin D, Wang P, Boudiffa M, Bellantuono I, Fukada Y, Boot-Handford RP, Meng QJ (2016). The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity. J Clin. Invest. 126 (1), 365-376.

Yagita K, Horie K, Koinuma S, Nakamura W, Yamanaka I, Urasaki A, Shigeyoshi Y, Kawakami K, Shimada S, Takeda J, Uchiyama Y. (2010). Development of the circadian oscillator during differentiation of mouse embryonic stem cells in vitro. PNAS. 107(8):3846.

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