New computational framework for the characterisation of next generation probiotics targeting autoimmune and inflammatory bowel disorders

Résumé

This PhD project aims to build the scientific basis to develop new functional foods based on bioactive peptides obtained from the genetic sequences of the human microbiome. These foods will be directed to the prevention of several gastrointestinal disorders of autoimmune and inflammatory nature, as well as to decrease the effects of the disease in patients. This will have a direct effect decreasing the economic burden of the treatments and increasing the quality of life of the patients. The proposed computational framework will be equipped to support the study of human gut microbiota interactions with the immune system and to manipulate aberrant immune responses. To this end, the PhD student will integrate both novel and state-of-the-art bioinformatics methods and tools for sequence analysis and protein characterisation with various well-established data integration and data mining methods. The PhD student will develop in silico tools to characterise encrypted peptides with potential bioactivity, firstly by studying their occurrence in the exoproteomes of the human microbiome, and thus obtain a database of peptides with different potential bioactivities. Moreover, functional analysis of proteome interactions will be pursued as means to reveal metabolic systems with greater prevalence among diseases progressing with inflammatory or autoimmune mechanisms, such as inflammatory bowel disease (IBD) and colo-rectal cancer (CRC). Further, this will help us to analyse nutrient-affected pathways in the human pathology. Most notably, the PhD student will investigate cross-feeding relationships between gut microbe enzymes and host carbohydrate metabolism enzymes, diet modulation and the use of probiotics in treating metabolic disorders. This project will shed light on our understanding of the human gut biology and cell cross-talk with food, probiotic and gut bacteria in the context of diseases such as IBD and CRC. Specifically, the new computational framework will equip researchers with the latest and more powerful means of in silico analysis and take the best possible advantage of public databases, enabling cutting-edge interdisciplinary research. This is of major interest since the number of people suffering from these diseases in Europe and other developed countries has been increasing during the last years and it is expected to continue growing in the future.