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Rhomboid-like proteins and the cell biology of signalling

  • Full or part time
    Prof M Freeman
  • Application Deadline
    Friday, January 10, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

The main questions we study are what cellular mechanisms regulate signalling between animal cells, and how does that signalling control biological functions like physiology, development and disease? Our current focus recently is the rhomboid-like superfamily of proteins. We initially discovered that rhomboids were novel intramembrane proteases, conserved across evolution, which regulate the production of extracellular signals. The rhomboids are now known to be involved with many biological processes including, for example, growth factor activation, mitochondrial function, host cell invasion by parasites and bacterial physiology. Given this range of functions it is clear that rhomboids also have potential medical significance.
More recently we have become interested in the much wider superfamily of rhomboid-like proteins, the majority of which are not proteases. We have studied a few examples and have uncovered roles in controlling the cellular fate of membrane proteins. We study the genetics, cell biology and biochemistry of rhomboid-like regulation and function, using a variety of systems including mice, Drosophila and human cells. Although our main effort is aimed at understanding fundamental cell biology, we are also pursuing the potential medical significance of our basic discoveries.

Funding Notes

4 Year DPhil Prize Studentships cover University fees, a tax free stipend of ~£17,009 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.

References

Künzel, U., Grieve, A. G., Meng, Y., Sieber, B., Cowley, S. A., and Freeman, M. (2018). FRMD8 promotes inflammatory and growth factor signalling by stabilising the iRhom/ADAM17 sheddase complex. Elife 7, 35012.

Grieve, A G, Xu, H, Kunzel, U, Bambrough, P, Sieber, B, and Freeman, M (2017). Phosphorylation of iRhom2 at the plasma membrane controls mammalian TACE-dependent inflammatory and growth factor signalling. Elife 6: e23968

Freeman M (2014). The rhomboid-like superfamily: Molecular mechanisms and biological roles. Annu Rev Cell Dev Biol 30: 235-254

Adrain C, Zettl M, Christova Y, Taylor N, Freeman M (2012). Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science 335: 225-228

How good is research at University of Oxford in Biological Sciences?

FTE Category A staff submitted: 223.80

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