Lymphoid tissue develops during embryonic development and as a result of chronic infections. This consists of networks of specialised mesenchymal-derived stromal cells that support and organize the adaptive immune system. Development of these tissues is a result of dynamic cellular interactions between haematopoietic cells and stromal cells. Gene-targeted mice have provided insight into the cellular interactions involved but have failed to lead to a complete understanding of lymph node organogenesis. Thus we wish to utilise simulation modelling to determine the role of deterministic forces in lymphoid tissue organogenesis. This project will involve the development of an agent based simulation of lymphoid tissue development utilizing primary data sets that we have collected; going through both the design of a model of lymphoid organogenesis in UML (primarily using state diagrams) and implementation of this to generate a functional model which will be utilised to test our hypothesis that deterministic forces (including the role of fluidic pressure, physical geometry and oxygen levels (physiological forces)) are critical in lymphoid tissue formation.
Kieran is also involved the development and maintenance of the dConsensus bioinformatic tool with collaborators at the University of California, San Diego. This is a web resource, used by those working in the structural biology field, that displays the results of calculations from multiple protein domain assignment algorithms and generates a domain assignment consensus with an associated reliability score. This provides insights into the fundamental units of protein structure so important to the study of evolutionary and functional relationships.
There will be two components to the PhD project.