About the Project
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
Debashis Sarker: Is a Consultant in Medical Oncology and a specialist in pancreatic cancer.
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:
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).
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.
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