Abstract
This thesis is written in publication format and comprises the work done in two main research lines: Study of the Cell Cycle regulation (Chapters 1-3) and The Integration of Metabolism and immunity (Chapters 4-7). Chapter 1 is a review article that collects relevant information on regulatory structures present in biological networks, using a Systems and Synthetic Biology approach. Chapter 2 analyses a minimal cell cycle network using the System Design Space (SDS) methodology, establishing under which conditions (parameter values) the network can exhibit bistability and oscillations. Chapter 3 uses the SDS approach to characterise the cell cycle cyclin waves in budding yeast mutant stains. Using mutant budding yeast frequency in population data provided by collaborators at the Imperial College London, it was possible to analyse how the deletion of key cell cycle genes affects the capacity of the cell to exhibit sustained oscillations and the shape of the cyclin waves. Chapter 4 is an editorial article reflecting on the importance of the balance of T cell phenotypes on health and disease, serving as the transition to the Metabolism and Immunity part of the thesis. Chapter 5 shows the use of Flux Balance Analysis (FBA) simulations to understand the response towards an experimental HIV vaccine. Starting from untargeted metabolomic data from patient serum samples, provided by collaborators at the University of Rochester it was possible to find metabolic pathways involved in the early reaction to the vaccine. Chapter 6 shows the analysis of the Priority Index Database for gene targets in autoimmune disorders, using the ranking of target genes as an input to establish similarities among autoimmune disorders and finding opportunities for drug repurposing. Finally, Chapter 7 is a perspective article that discusses the importance of addressing the metabolism when studying immune disorders, particularly the link between metabolism inflammation and ageing.