• Computational Modelling Folate Metabolism and DNA Methylation: Implications for Understanding Health and Ageing

      Mc Auley, Mark T.; Mooney, Kathleen M.; Salcedo-Sora, J. Enrique; University of Chester; Edge Hill University; Liverpool Hope University (Oxford University Press, 2016-12-21)
      Dietary folates have a key role to play in health as deficiencies in the intake of these B vitamins have been implicated in a wide variety of clinical conditions. The reason for this is folates function as single carbon donors in the synthesis of methionine and nucleotides. Moreover, folates have a vital role to play in the epigenetics of mammalian cells by supplying methyl groups for DNA methylation reactions. Intriguingly, a growing body of experimental evidence suggests DNA methylation status could be a central modulator of the ageing process. This has important health implications because the methylation status of the human genome could be used to infer age-related disease risk. Thus, it is imperative we further our understanding of the processes which underpin DNA methylation and how these intersect with folate metabolism and ageing. The biochemical and molecular mechanisms which underpin these processes are complex. However, computational modelling offers an ideal framework for handling this complexity. A number of computational models have been assembled over the years, but to date no model has represented the full scope of the interaction between the folate cycle and the reactions which govern the DNA methylation cycle. In this review we will discuss several of the models which have been developed to represent these systems. In addition we will present a rationale for developing a combined model of folate metabolism and the DNA methylation cycle.
    • Computer Modelling for Nutritionists

      Mc Auley, Mark Tomás; University of Chester
      This book is about computational modelling of nutrient focused biological systems. The book is aimed at students, researchers, and those with an interest in learning how to build a computational model. The book is the product of many years of teaching computational modelling to undergraduates, postgraduates, and researchers with limited, or no background in computational modelling. What I learned from these experiences is those new to modelling are invariably apprehensive about it, and approach it with a degree of trepidation, or even scepticism. However, from tentative initial steps, they quickly realize that modelling is not as challenging, or as academically intimidating as they initially perceive it; and after gaining familiarity with the essential components of model building they rapidly become cognisant, that it offers an alternative lens to view a biological system, and learn new insights about its underlying dynamic behaviour. In this book I provide a practical introduction to modelling, for those who are interested in exploring the dynamics of nutrient based systems. My rationale for undertaking this project is based on my experience of interacting with nutritionists in recent years. As a result of many fruitful discussions I identified a growing need for a book of this nature, which is specifically tailored to nutritionists. My aims are to provide the reader with a solid grounding in computational modelling, and how it dovetails within the burgeoning field of systems biology. For the reader this will involve learning how a model is assembled, what software tools are available for model building, what the different paradigms are for simulating a model, and how to analyse and interpret the output from in silico simulations. The only expectation I make of you, as a reader, is that you are enthusiastic about learning how to use new software tools. In exchange for your engagement I will provide you with ample practical exercises, which will help to consolidate your learning, and will make your computational modelling journey a rewarding and enjoyable experience.