COLOSSUS partner Dr Dirk Fey, UCD explains Computational Modelling in Systems Biology

Dr Dirk Fey of the University College Dublin explains some of the techniques being used in the COLOSSUS Project (https://www.colossusproject.eu/).

In biology, things seldom work in isolation. Individual molecular structures, like genes and proteins, work together to function. In turn, cells work as part of a wider tissue, organ or system in the body. Likewise, organisms interact with each other in ecosystems and societies. Systems Biology Ireland (SBI, https://www.ucd.ie/sbi/) uses mathematical and computer modelling to help make sense of this complexity. Founded in 2009, SBI is situated on the University College Dublin campus.

In collaboration with COLOSSUS partners, our ‘dry lab’ research uses a series of observations or measurements from biological samples and builds the data into a computer model to predict how the biological molecules interact. We use machine learning or artificial intelligence (AI) to show how molecular interactions might change in an MSS RAS mt colorectal cancer setting, and integrate data from the cells into larger systems such as tissues, organs or the body as a whole. This effective, iterative scientific process helps inform which laboratory experiments should be performed next.

In cancer, tumour cells in the body ‘go rogue’. Cancer cells stop responding to the body’s communication signals in the way that healthy cells do. This is a result of a ‘rewiring’ of the cells internal signaling networks and an alteration in how cells communicate and grow within their network. At SBI, we seek to better understand these changes in order to identify more effective combinations of existing anti-cancer drugs that are more e#cacious and with less toxic side effects for patients. We also help design new anti-cancer drugs by identifying nodes in cancer signaling to predict what could happen if they become disrupted.

In addition to myself working on the COLOSSUS project at SBI, there are PI Prof. Walter Kolch, Dr David Gomez-Matallanas, and PhD candidates Aoife Nolan and Annabelle Nwaokorie. Prof. Kolch oversees the overall project, and we work very closely with Dr Gomez and Aoife Nolan who drive SBI’s experimental work on the project, providing invaluable data for building the models. Annabelle Nwaokorie and I then take these data to build computational models of key colorectal cancer signalling networks. Annabelle’s approach is to combine data-driven (machine learning) modelling approaches with knowledge-driven mathematical modelling, and in this way build better, more detailed models. We hope that one day these models can be used to predict the therapy responses of patients and guide their treatments.

  COLOSSUS has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no 754923. The material presented and views expressed here are the responsibility of the author(s) only. The EU Commission takes no responsibility for any use made of the information set out.