"Role of altered lysosome positioning in bladder cancer progression (2017-09-SCHAUER)" project details

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General information

Application closed

2017-09-SCHAUER

Cancer, Lysosomes, Micropatterning, Secretion, Trafficking

Role of altered lysosome positioning in bladder cancer progression

Director(s) and team

Kristine Schauer

Structure-function relationship of cell architecture

Abstract

Description of the PhD thesis project
The PhD project will be carried out in the team ”Structure-function relationship of cell architecture” run by K. Schauer that is part of the “Molecular mechanisms of intracellular transport” laboratory headed by B. Goud. The team investigates how intracellular organization and interorganelle communication controls intracellular trafficking. We study molecular mechanisms that regulate global cell organization and the role of cell architecture in health and disease. Building on normalized cell culture on adhesive micropatterns, we have developed a prototype approach based on probabilistic mapping that gives us the unique possibility to reveal how different compartments are organized in the cellular space. Importantly, we found that each compartment has a characteristic, well-defined, stable and reproducible organization. Because intracellular changes are poorly defined in cancer, we have recently applied our method to several bladder cancer cell lines to investigate intracellular alterations during cancer progression.

Comparing density maps of different organelles in normal and bladder cancer cells, we have evidenced that the lysosomal compartment reveals striking differences in advanced cancer cell lines. The PhD candidate will investigate how the observed changes lead to altered cell behavior that is characteristic for cancer cells, focusing on cell invasion. We will study the molecular mechanisms underlying intracellular changes investigating the role of key trafficking regulators. Additionally, we will explore which extrinsic cues facilitate cancerogenesis.

This project will shed light on basic mechanisms that govern cellular morphogenetic processes driving cancer progression. The PhD will become acquainted with state of the art light imaging methods that will be complemented with computational analysis. Furthermore, the PhD candidate will develop micromanipulation techniques for cell culture and cell perturbations at the single-cell level.

International, interdisciplinary & intersectoral aspects of the project

  • International:
We will collaborate with several international teams (e.g. Dr Braulke, University Medical Center Hamburg-Eppendorf, Germany, and Dr Kapitein (Utrecht University, Netherland). We anticipate that the selected PhD candidate will visit these groups to discuss and pursue experiments.  

  • Intersectoral:
We anticipate to test and further develop confinement tools on several cancer cell lines in collaboration with our industrial partner 4Dcell, a dynamic start up in the Parisian region.

  • Interdisciplinary:
We will combine confinement tools with high-end single cell imaging approaches, including optogenetics for precise spatial and temporal control in cell biological applications.

Recent publications
1. Alanko J, Mai A, Jacquemet G, Schauer K, Kaukonen R, Saari M, Goud B, Ivaska J. Integrin endosomal signalling suppresses anoikis. Nat Cell Biol. 2015, Nov;17(11):1412-21. doi: 10.1038/ncb3250.
2. Grossier JP, Xouri G, Goud B, Schauer K. Cell adhesion defines the topology of endocytosis and signaling. EMBO J. 2014, Jan 7;33(1):35-45. doi: 10.1002/embj.201385284.
3. Schauer K, Grossier JP, Duong T, Chapuis V, Degot S, Lescure A, Del Nery E, Goud B. A novel organelle map framework for high-content cell morphology analysis in high throughput. J Biomol Screen. 2014, Feb;19(2):317-24. doi: 10.1177/1087057113497399.
4. Duong T, Goud B, Schauer K. Closed-form density-based framework for automatic detection of cellular morphology changes. Proc Natl Acad Sci U S A. 2012, May 29;109(22):8382-7. doi: 10.1073/pnas.1117796109.
5. Schauer K, Duong T, Bleakley K, Bardin S, Bornens M, Goud B. Probabilistic density maps to study global endomembrane organization. Nat Methods. 2010, Jul;7(7):560-6. doi: 10.1038/nmeth.1462.

Requirements to apply for the PhD thesis project

Applicants should have a strong interest in quantitative understanding of fundamental cell biological processes. A strong capacity for independent and creative thinking as well as for team work is needed. Background in biophysics and engineering will be a plus. The project strongly relies on imaging and image analysis for which the applicant required some experience with programming or strong motivation to learn.