T cells under pressure King’s College London in United Kingdom

T cells under pressure

Cytotoxic CD8 T cells (CTLs) are important players in the immune response against cancer. Once activated by antigen, they migrate into tumours, adhere to their target cells and kill them by secreting a cocktail of cytotoxic enzymes. These target tissues are often biomechanically altered and much stiffer than healthy tissues, which in the case of cancer cells has been shown to affect their ability to migrate and metastasise. Preliminary date from the lab suggests that these forces can constitute a biomechanical immune evasion strategy by inhibiting the ability of CTLs to regulate their volume, polarise, create mechanical force and kill target cells.

The student will extend this work and study the impact of tissue mechanics on CTL function by first developing in vitro hydrogel systems that match the elastic, viscoelastic and osmotic properties encountered by CTLs in healthy and tumour tissues. These assays will then be used to study the impact of tissue mechanics on the ability of CTLs to migrate, signal, form an immune synapse with target cells, generate mechanical force and eventually eliminate the cancerous target cells.

This project is at the interface of material sciences, biophysics and immunology and will be supervised by an experienced team of Robert Köchl (immunology) Eileen Gentleman (bioengineering and biomechanics) , Leone Rossetti (traction force microscopy, biophysics). The student will be embedded in highly supportive research environment working along a postdoctoral research assistant and other PhD students in the Köchl, Rossetti and Gentleman labs.

Research training

• EPSRC-funded PhD programme with ample training opportunities within the university, and access to university/department-wide seminars by world leading scientists.
• Training in mouse immunology including (harvesting, activating and culturing primary mouse T cells, as well as functional assays to analyse cell migration and cytoxicity).
• Training in bioengineering and biomechanics (Generation of in vitro hydrogels to mimic the tumour microenvironment, measuring mechanical properties of hydrogels and forces generated by T cells).
• High level training in cutting-edge imaging approaches, potentially including quantitative live imaging using lattice light sheet microscopy, super resolution imaging modalities.

Person specification

• This is a highly innovative project, so a suitable student must be motivated by challenges, cutting-edge science and technology. Interested candidates are strongly encouraged to contact Robert Köchl and the supervisory team by email directly.
• MSc or equivalent degree in Physics or Biology, or related discipline, either completed or expected to be completed with at least a 2.1.
• Ability to work at the interface of different disciplines, such as biomechanics, bioengineering and immunology