Phil Hodgkin-Projects

Phil Hodgkin-Projects

Projects

Super Content: 
Immunology researcher team

Our research have shown that some immune cells have some control over their own destiny.

A computational model of the immune system

The development of mathematical models of the T and B cell adaptive immune response has developed rapidly over the last several years and the probabilistic principles for codifying modules of cellular behavior have proved increasingly successful. All members of the lab work either with, or on improving such models directly. New resources are being developed as software for the immunology community. Experiments to inform the models and to test predictions are made from single cell tracking, from cell division and differentiation tracking and from fate mapping performed both in vitro and in vivo.

Members: Mark Dowling, Andrey Kan, John Markham, Ken Duffy (National University of Ireland). 

The biology of T and B cells and the cellular calculus

There is still much to learn about the normal biology of both T and B lymphocytes in the immune response.  We are particularly keen to understand how cells add signals together and adjust to changing levels and combinations of the many different cytokines and costimuli on offer during an immune challenge.  To reveal this ‘cellular calculus’ we measure cell behavior, at single cell and population level to learn the rules of addition and to predict the net outcomes. The effects of drugs and genetic manipulations on modular components of the cell are also being measured with the aim to develop a principle for predictive immunotherapy and in silico drug screening.

Members: The model team: Mark Dowling, Andrey Kan, John Markham, Ken Duffy (National University of Ireland) with the experimental team – Su Heinzel, Julia Marchingo, Jie Zhou, Bryan Lye.

The biology of cancer and chemotherapy

The basic model of cellular mechanics we have developed, the Cyton sees autonomous processes governing cell fates, such as division and death, placed in competition within each cell.  We are exploring this hypothesis in the context of cancer cell biology to attempt a general theory of the regulation of cell fates.  This will help to understand the effects of deregulation of the cell cycle in cancer cells and to better target the use of chemotherapeutic drugs.

Members: Mark Dowling, Kim Pham, Jie Zhou, Ken Duffy (National University of Ireland) 

Variation in the human immune system and its importance to disease

Our principles of cellular calculus and single cell behavior have been developed using model systems.  We are asking whether the same principles operate for people and the quantitative methods we have developed could help stratify and screen for genetic deficiencies and susceptibilities. Importantly we aim to identify how multiple small quantitative changes in cellular circuits can add up to powerful immune disorders such as autoimmunity. Our first target is to examine Common Variable Immunodeficiency and move from there to more complex immune disorders.

Members: Vanessa Bryant, Su Heinzel and Charlotte Slade