Coventry University Featured PhD Programmes
Engineering and Physical Sciences Research Council Featured PhD Programmes
Cardiff University Featured PhD Programmes

Advanced live cell imaging based characterisation of a novel Scar/WAVE and Ena/VASP ligand in 3D pancreatic cancer cell invasion.


Health Schools

Sunday, November 29, 2020 Competition Funded PhD Project (European/UK Students Only)

About the Project

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with very low survival rate due to the uncontrolled cell proliferation and metastatic spread. Metastasis is driven by changes in the regulation of the actin cytoskeleton, which provides the force for cell migration. Surprisingly little is known about the molecular details of how regulation of the actin cytoskeleton is changed to allow PDAC cells to become motile and how this defines the mode of invasion into 3D matrix from PDAC organoids. We have identified a novel regulator of the actin cytoskeleton and cell migration which binds to two important actin effectors, Ena/VASP and Scar/WAVE-Arp2/3 complex and which is phosphorylated by the proto-oncogenes, the tyrosine kinases c-Src and c-Abl. We also know that expression of this novel protein positively correlates with reduced survival of patients with PDAC.
In this project you will explore the function of this novel protein in invasion from PDAC spheroids and organoids, utilizing novel optical imaging strategies based on light-sheet fluorescence microscopy. The system will enable high-speed volumetric-imaging allowing quantification of invasion into the surrounding matrix in high detail. Combining FRET-FLIM capabilities of this state-of-the-art microscope with image-based analysis tools written in MATLAB/Python will permit quantification of the activity of the Arp2/3 complex in the invading cells using a novel FRET-FLIM biosensor. You will use a combination of genetic (CRISPR-Cas9), biochemical and imaging approaches to explore regulation of the interactions of this novel protein with Ena/VASP and Scar/WAVE-Arp2/3 complex by Src and Abl and the functional significance of it.

You will be co-supervised by three supervisors:
Matthias Krause (Cell biologist), Simon Poland (Physicist), Debashis Sarker (Consultant in Medical Oncology; specialist in pancreatic cancer)

You will join friendly, interactive, science driven labs:
The Krause lab (https://www.krauselab.org), which is embedded in the Cytoskeleton and Cell Motility Section of the Randall Centre at King’s College London:
(https://www.kcl.ac.uk/lsm/research/divisions/randall/research/sections/motility/index.aspx) with 9 laboratories all interested in the cytoskeleton and cell motility with joint meetings and journal clubs. Furthermore, we are part of the London wide London Cell Motility Club, which Matthias is organizing: https://cytoskeleton.wixsite.com/londoncellmotility.

The Poland lab: Simon Poland is just starting his lab and is an expert in advanced microscopy development. https://kclpure.kcl.ac.uk/portal/en/persons/simon-poland(fdd69239-a2b8-438e-b593-ed7b832d95c9).html
https://www.linkedin.com/in/simon-poland-257b6183/?originalSubdomain=uk

Debashis Sarker: Is a Consultant in Medical Oncology and a specialist in pancreatic cancer.
https://www.kcl.ac.uk/people/debashis-sarker
https://kclpure.kcl.ac.uk/portal/debashis.sarker.html

Funding Notes

Funding for entry in October 2021:
This PhD student project is part of the MRC-DTP program of King’s College London for start in October 2021 and competitively funded. Please see details on and apply directly on the MRC-DTP King’s College London website:
View Website

The studentship application process for 2021 entry will start on October 19th:

Studentship Applications Open: Monday 19th October 2020
Studentship Applications Close: Sunday 29th November 2020, 23:59
Interviews: Wednesday 27th and Thursday 28th January 2021
There will be opportunities for candidates to meet supervisors on or before the interview days (Wednesday 27th and Thursday 28th January 2021).

References

Ah-Lai Law, Shamsinar Jalal, Fuad Mosis, Tommy Pallett, Ahmad Guni, Simon Brayford, Lawrence Yolland, Stefania Marcotti, James A. Levitt, Simon P. Poland, Maia Rowe-Sampson, Anett Jandke, Robert Köchl, Giordano Pula, Simon M. Ameer-Beg, Brian Marc Stramer, Matthias Krause (2020) Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration. https://www.biorxiv.org/content/10.1101/2020.05.11.083030v1

Carmona G, Perera U, Gillett C, Naba A, Law AL, Sharma VP, Wang J, Wyckoff J, Balsamo M, Mosis F, De Piano M, Monypenny J, Woodman N, McConnell RE, Mouneimne G, Van Hemelrijck M, Cao Y, Condeelis J, Hynes RO, Gertler FB, Krause M. (2016) Lamellipodin promotes invasive 3D cancer cell migration via regulated interactions with Ena/VASP and SCAR/WAVE. Oncogene. 2016 Sep 29;35(39):5155-69.

Poland, S P., Krstajić, N., Monypenny, J., Coelho, S., Tyndall, D., Walker, R. J., Devauges, V., Richardson, J., Dutton, N., Barber, P., Li, D-D, Suhling, K., Ng, T., Henderson, R. K. and Ameer-Beg, S. M., "A high speed multifocal multiphoton fluorescence lifetime imaging microscope for live-cell FRET imaging." Biomedical optics express 6, no. 2 (2015): 277-296.
Krause, M. and Gautreau, A. (2014) Steering cell migration: lamellipodium dynamics and the regulation of directional persistence. Nature Reviews Molecular Cell Biology, 15, 577-90 (2014).

Law, A., Vehlow, A., Kotini, M., Dodgson, L., Soong, D., Theveneau, E., Bodo, C., Taylor, E., Navarro, C., Perera, U., Michael, M., Dunn, G.A., Bennett, D., Mayor, R., and Krause M. (2013) Lamellipodin and the Scar/WAVE complex cooperate to regulate cell migration in vivo. Journal of Cell Biology, 203(4), 673-689.

Email Now

Insert previous message below for editing? 
You haven’t included a message. Providing a specific message means universities will take your enquiry more seriously and helps them provide the information you need.
Why not add a message here

The information you submit to King’s College London will only be used by them or their data partners to deal with your enquiry, according to their privacy notice. For more information on how we use and store your data, please read our privacy statement.

* required field

Your enquiry has been emailed successfully



Search Suggestions

Search Suggestions

Based on your current searches we recommend the following search filters.



FindAPhD. Copyright 2005-2020
All rights reserved.