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Metabolic control of the bone marrow microenvironment

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  • Full or part time
    Dr S Ramasamy
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

In the skeletal system, blood vessels play a central role in the maintenance of microenvironments (niches) required for regulating osteogenesis and haematopoiesis. Blood vessels supply oxygen and nutrients to various microenvironments in bone. However, it is still not known how blood vessels recognize and regulate distinct metabolic demands in microenvironments. In this project, we will investigate the role of endothelial cell metabolism in regulating bone marrow microenvironments.

The project will involve mouse genetics to specifically manipulate endothelial cells to understand the changes in mesenchymal and haematopoietic compartment of the bone marrow vascular niche. It also involves a powerful combination of novel approaches such as advanced 3D imaging, intra-vital imaging, and transcriptomics to investigate the function of blood vessels in bone metabolism. The study will not only unravel how bone interacts with the whole-body physiology, but also helps understanding the mechanism that causes age-related loss in bone mass and defective haematopoiesis.

Funding Notes

This project is competition funded for students worldwide.

If successful the student would receive full tuition fee payment for 3.5 years as well as a tax free stipend amounting to £21,000pa paid in monthly instalments for the duration of their studentship.

Whilst Overseas Students are eligible, funding is more limited so only exceptional OS students will be considered.

References

Ramasamy SK, Kusumbe AP, Itkin T, Gur-Cohen S, Lapidot T, Adams RH (2016) Regulation of Hematopoiesis and Osteogenesis by Blood Vessel-Derived Signals. Annu Rev Cell Dev Biol. 2016

Ramasamy SK, Kusumbe AP, Adams RH (2015) Regulation of tissue morphogenesis by endothelial-derived signals. Trends Cell Biol. 52: 148-157.

Ramasamy SK*, Kusumbe AP*, Wang L, Adams RH (2014) Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature 507: 376-380.

Kusumbe AP*, Ramasamy SK*, Adams RH (2014) Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone. Nature 507: 323-328.
* Equal contributions

Kusumbe AP, Ramasamy SK, Itkin T, Mäe MA, Langen UH, Betsholtz C, Lapidot T, Adams RH (2016) Age-dependent modulation of vascular niches for haematopoietic stem cells. Nature 532:380-384.

Itkin T, Gur-Cohen S, Spencer JA, Schajnovitz A, Ramasamy SK, Kusumbe AP, Ledergor G, Jung Y, Milo I, Poulos MG, Kalinkovich A, Ludin A, Kollet O, Shakhar G, Butler JM, Rafii S, Adams RH, Scadden DT, Lin CP, Lapidot T (2016) Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature 532:323-328.

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