Phd projects in Immunology

Stochastic models of the adaptive immune system

Supervisors: Grant Lythe and C. Molina-Paris
The goal of this project is to develop mathematical and computational models to help understand how the immune system maintains its diversity of millions of lymphocyte populations, able to protect against pathogens while avoiding auto-immune diseases. The processes of positive and negative selection in the thymus will be studied with stochastic modelling techniques, including computational modelling and analysis of experimental data.

Mathematical modelling of vascular endothelial growth factors and receptors

Supervisors: C. Molina-Paris, Dr Vas Ponnambalam and Grant Lythe
Multicellular organisms contain biological tubes such as blood vessels that are used to move molecules, cells and fluids to different tissues. Endothelial cells that line every blood vessel can bind growth factors which regulate new blood vessel formation and vascular function. The vascular endothelial growth factor A (VEGF-A) binds membrane receptor tyrosine kinases (VEGFR1, VEGFR2) and regulates many aspects of vascular function. Dysfunction of this VEGF-VEGFR system can lead to diseases such as cancer.
This student will use experimental data generated in the Endothelial Cell Biology Unit (Faculty of Biological Sciences, University of Leeds) and put it into a quantitative framework using mathematical modelling with spatial and temporal constraints. The PhD student will derive mathematical models of VEGFR synthesis, endocytosis and degradation. The systems biology approach integrates experimental and modelling-based data. The goal is cellular output prediction in silico and experimental testing to validate model robustness.

From haematopoietic stem cells to natural killer cells

Supervisors: Grant Lythe, C. Molina-Paris and Graham Cook
Haematopoietic stem cells (HSC) give rise to all blood cell lineages. HSC undergo asymetric cell division; one daughter cell differentiates into a mature blood cell whilst the other remains an HSC, ensuring a lifelong supply of blood cells. We are interested in a population of white blood cells known as natural killer (NK) cells. NK cells have attracted significant clinical interest because they have an innate ability to kill infected cells and tumour cells and they are under investigation as a useful therapeutic tool, particularly in cancer treatment. Interestingly, like T lymphocytes, NK cells appear to undergo an education-like step in their development which ensures that they do not attack healthy cells. Studying the development pathway of NK cells from HSC promises to reveal how these education processes generate a useful repertoire of NK cells and how this might be exploited for therapy in the future. The student will use stochastic branching processes and evolutionary dynamics in the mathematical modelling of these systems to investigate the pathway of NK cell development from HSCs. The project is a collaboration between mathematicians and immunologists in Leeds.