Systems Biology Project

Title Combinatorial responses of fungal pathogens to their human hosts: an integrative systems biology approach (CRISP).

Principal Investigator Professor Ken Haynes

Summary Life on this planet is dependent upon environmental adaptation.  Biological systems are constantly subjected to a wide variety of external stimuli and challenges.  Many of these change continuously and in order to survive the organism must respond appropriately to each new set of circumstances.  It is however difficult for scientists to study such complex perturbations and so typically researchers have focused on one stimulus at a time.  Whilst this has yielded major biological insights, to make further progress we need to develop approaches to studying combinations of several simultaneous perturbations.  This cannot be done using conventional experimental techniques alone.  These need to be supplemented by mathematical and computational modelling methods, which can integrate data from different experiments, reveal hidden patterns, explain apparently contradictory results and suggest new biological hypotheses.

CRISP is applying Integrative Systems Biology to understand how pathogenic fungi respond to the combinations of different stresses they encounter when they invade a human host.  We are focusing on two major fungal pathogens of humans, Candida albicans and Candida glabrata.  These fungi cause frequent oral and vaginal infections (thrush) and life-threatening infections in transplant and cancer patients.  When these fungi invade a patient, the immune system normally responds with a variety of defensive counter-measures that are designed to kill them.  For Candida albicans and Candida glabrata these defences are essentially equivalent to environmental stresses, and the fungi activate damage limitation strategies.  We are studying how these medically important pathogens respond to the combinations of stress they experience in their human host.

CRISP is a collaboration between the University of Aberdeen, Imperial College London and the University of Exeter.

Funding Body BBSRC

Timescale 2008 - 2013

Value £5.6m