Scientific background
γδ T cells form a separate branch of the adaptive immune system, next to B cells and αβ T cells. Although γδ T cells are still poorly understood, they show great potential for usage in the cancer therapies. A problem when targeting tumors is that cancer cells can hide from the immune system, but γδ T cells have the special capability to detect these hidden cancer cells. Like αβ T cells, γδ T cells bind antigens with their T cell receptor (TCR). It is however unclear how the γδ T cell receptor functions, and whether its triggering mechanism is similar to that of the still not fully understood activation mechanism of the αβ TCR. A molecular understanding of the γδ T cell receptor will be vital for the development of more effective treatments.
PhD project description
In this PhD project the γδ T cell receptor will be studied using molecular dynamics simulations. With molecular dynamics simulations one can simulate how proteins and lipids interact. One can think of it as a “computational microscope” which allows one to study protein behavior with atomistic resolution.
The goal of this project is to get 1) an understanding of the γδ TCR using molecular dynamics simulations and 2) design clinically relevant γδ T cell receptors for usage in therapies. The project will be performed in collaboration with experimental partners, which gives the unique opportunity to really work at the interface of theoretical and experimental immunology.
Required profile of the candidate
The ideal candidate should have:
· An affinity for the fields of biology, chemistry, computer science and physics
· The ability to work interdisciplinary
· First experience with simulations (as a plus)
· Curiosity, eye for detail and scientific rigor
· Enthusiasm and communication skills
· Creativity and a flexible mindset
Publications relevant to the project
Hu, Y., Hu, Q., Li, Y., Lu, L., Xiang, Z., Yin, Z., Kabelitz, D., and Wu, Y., γδ T Cells: Origin and Fate, Subsets, Diseases and Immunotherapy. Signal transduction and targeted therapy 8, 434 (2023). doi: 10.1038/s41392-023-01653-8
van Eerden, F.J., Sherif, A.A., Llamas-Covarrubias, M.A., Millius, A., Lu, X., Ishizuka, S., Yamasaki, S., and Standley, D.M., TCR-pMHC Complex Formation Triggers CD3 Dynamics. eLife 12, 0 (2023). doi: 10.7554/eLife.88065.1
Xin, W., Huang, B., Chi, X., Liu, Y., Xu, M., Zhang, Y., Li, X., Su, Q., and Zhou, Q., Structures of Human γδ T Cell Receptor–CD3 Complex. Nature 630, 222–229 (2024). doi: 10.1038/s41586-024-07439-4