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How the Extracellular Matrix regulates cellular and organ growth


   Faculty of Science, Engineering and Computing

  ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

What is the reason why cells can suddenly switch to uncontrolled cellular growth? What causes the normal formation of cellular contacts and organs to stop growing when reaching their normal size to ignore normal signals and multiply uncontrollably?

The role of signaling pathways in the correct orientation of cells and the orchestrated multiplication of cells to allow an organ to grow and reach a certain size. This is an important question as not only are a number of cancers de-differentiated and thus are deemed more clinically concerning due to their loss of polarity, but also prevention of uncontrolled cellular growth is a key requirement the therapeutic treatment of cancer.

An important pathway in the development of cell-cell contact and polarity establishment is the Extracellular Matrix (ECM) Misregulation of any of the key components of the ECM can cause detrimental effects to such important processes as cellular adhesion and polarity causing cells to migrate uncontrollably and can result in a much more aggressive form of cancer. It has been already shown that the Hippo signalling pathway was important for organ growth control. Initially discovered in the fruit fly, the Hippo signalling pathway was found to be conserved in mammals. It has been found that the ECM may regulate the Hippo pathway effector YAP but nothing is known about how certain novel components regulate the Hippo signalling pathway, this knowledge will be crucial to establish if affecting these components can affect disease progression in cancer (1,2).

What is also found to be important in cancer progression is the breakdown of cytoskeletal components (3) and the ECM may play an intricate role in the regulation of these cytoskeletal components (4).

The MRes or PhD will involve mainly the use of mammalian cell culture as a model system, while utilizing such techniques as Immunoflourescence, siRNA transfections, generation of plasmids, Immunoblotting, scratch assays and target gene readouts. These planned techniques are used commonly in our research and some of them can be found in our list of key publications.

For entering a PhD or an MPhil, the entry requirement is a minimum of a 2:1 at undergraduate level or equivalent, and preferably an MSc in a Biological or Life Science subject. Research experience in Biochemistry, Cancer Biology or Molecular Biology is desirable.


Funding Notes

Please note: this is a self funded position which typically involves tuition fees, and bench fees. please enquire for an estimate for these.

For a PhD position:

The student will be registered for an MPhil. For progression to a PhD, a written thesis and viva on their research must be attempted after 12 months. this will be assessed by two examiners. If the student is successful then they will be upgraded to a PhD.

MPhil : 2 Years Full Time
PhD: Three Years Full Time.

MRes: One year Full time


References

(1) Vincent-Mistiaen Z*, Elbediwy A*, Vanyai H, Cotton J, Stamp G, Nye E, Spencer-Dene B, Thomas GJ, Mao J, Thompson B.
YAP drives cutaneous squamous cell carcinoma formation and progression.
Elife. 2018 Sep 20;7. pii: e33304. doi: 10.7554/eLife.33304.

(2) Elbediwy A, Vanyai H, Diaz-de-la-Loza MD, Frith D, Snijders AP, Thompson BJ
Enigma proteins regulate YAP mechanotransduction
J Cell Sci. 2018 Nov 22;131(22). pii: jcs221788. doi: 10.1242/jcs.221788

(3) Fletcher GC*, Elbediwy A*, Khanal I*, Ribeiro PS*, Tapon N, Thompson BJ.
The Spectrin cytoskeleton regulates the Hippo signalling pathway.
EMBO J. 2015 Feb 23. pii: e201489642

(4) Elbediwy A*, Vincent-Mistiaen ZI*, Spencer-Dene B, Stone RK, Boeing S, Wculek SK, Cordero J, Tan EH, Ridgway R, Brunton VG, Sahai E, Gerhardt H, Behrens A, Malanchi I, Sansom OJ, Thompson BJ.
Integrin signalling regulates YAP and TAZ to control skin homeostasis.
Development. 2016 May 15;143(10):1674-87. doi: 10.1242/dev.133728. Epub 2016 Mar 17.

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