Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2022 and will register for their PhD at one of the Crick partner universities (King’s College London).
This 4-year joint Crick PhD studentship is offered in the labs of Dr Alberto Elusegui-Artola’s Group and Prof Jody Rosenblatt based at the Francis Crick Institute (the Crick).
Background: Epithelial cells form a tight barrier that covers all our tissues and organs as well as perform several critical functions that include protection, secretion, absorption, excretion, filtration, diffusion or secretion, absorption or sensory reception. In order to be able to perform these functions, epithelial cells have to be able to remove dead or unwanted cells from the epithelium while maintaining a tight barrier. This key process is known as cell extrusion [1, 2]. Cell extrusion is tightly regulated in healthy tissues but is critically disturbed during cancer, leading to unconventional cell extrusion back into the tissue, enabling invasion [3]. This aberrant extrusion results from physical and chemical changes during cancer progression. One possibility is that cell attachment to the matrix may control the direction a cell extrudes, where tighter adhesions would promote basal extrusion and fewer, apical extrusion. Additionally, the Rosenblatt lab has found that matrix stiffness mechanically distorts cells, promoting their differentiation into mesenchymal cell types. This project aims to understand how adhesions forces regulate cell extrusion in healthy tissue versus cancer.
Description: To accomplish this project's goals, we will use biophysical and quantitative tools [4, 5] and computational modelling to investigate the principles that govern the interplay between chemical and physical cues in cell extrusion. We will use traction force microscopy to investigate adhesion changes in apical versus basal extrusion. The student will also grow epithelia in 2D and 3D matrices with different mechanical properties to understand the mechanisms that regulate cell extrusion in cancer. A combined approach using RNA sequencing and systematic molecular perturbations will be used to identify the molecules intrinsic to basal versus apical extrusion. Then, we will confirm the role of any candidate molecules in cell culture and zebrafish using knockdown strategies. The precise details of the project will be decided in consultation with the supervisor and the rest of the team.
Candidate background
The candidate should be enthusiastic and motivated with a strong interest in biomechanical biology and its roles in disease and normal tissue homeostasis. This project would suit candidates with a background in bioengineering, biology, biophysics, biochemistry. Technical expertise in imaging methods, molecular biology or biophysical techniques is advantageous but is not a prerequisite. A background in quantitative biology would be an asset. The student should also be open to new approaches to blend concepts from two labs and be able to work in a team environment.
Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.
APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘INSTITUTION WEBSITE’ LINK ABOVE) BY 12:00 (NOON) 11 November 2021. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
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