Project acronym BugTheDrug
Project Predicting the effects of gut microbiota and diet on an individual’s drug response and safety
Researcher (PI) Ines THIELE
Host Institution (HI) NATIONAL UNIVERSITY OF IRELAND GALWAY
Country Ireland
Call Details Starting Grant (StG), LS7, ERC-2017-STG
Summary Precision medicine is an emerging paradigm that aims at maximizing the benefits and minimizing the harm of drugs. Realistic mechanistic models are needed to understand and limit heterogeneity in drug responses. Consequently, novel approaches are required that explicitly account for individual variations in response to environmental influences, in addition to genetic variation. The human gut microbiota metabolizes drugs and is modulated by diet, and it exhibits significant variation among individuals. However, the influence of the gut microbiota on drug failure or drug side effects is under-researched. In this study, I will combine whole-body, genome-scale molecular resolution modeling of human metabolism and human gut microbial metabolism, which represents a network of genes, proteins, and biochemical reactions, with physiological, clinically relevant modeling of drug responses. I will perform two pilot studies on human subjects to illustrate that this innovative, versatile computational modeling framework can be used to stratify patients prior to drug prescription and to optimize drug bioavailability through personalized dietary intervention. With these studies, BugTheDrug will advance mechanistic understanding of drug-microbiota-diet interactions and their contribution to individual drug responses. I will perform the first integration of cutting-edge approaches and novel insights from four distinct research areas: systems biology, quantitative systems pharmacology, microbiology, and nutrition. BugTheDrug conceptually and technologically addresses the demand for novel approaches to the study of individual variability, thereby providing breakthrough support for progress in precision medicine.
Summary
Precision medicine is an emerging paradigm that aims at maximizing the benefits and minimizing the harm of drugs. Realistic mechanistic models are needed to understand and limit heterogeneity in drug responses. Consequently, novel approaches are required that explicitly account for individual variations in response to environmental influences, in addition to genetic variation. The human gut microbiota metabolizes drugs and is modulated by diet, and it exhibits significant variation among individuals. However, the influence of the gut microbiota on drug failure or drug side effects is under-researched. In this study, I will combine whole-body, genome-scale molecular resolution modeling of human metabolism and human gut microbial metabolism, which represents a network of genes, proteins, and biochemical reactions, with physiological, clinically relevant modeling of drug responses. I will perform two pilot studies on human subjects to illustrate that this innovative, versatile computational modeling framework can be used to stratify patients prior to drug prescription and to optimize drug bioavailability through personalized dietary intervention. With these studies, BugTheDrug will advance mechanistic understanding of drug-microbiota-diet interactions and their contribution to individual drug responses. I will perform the first integration of cutting-edge approaches and novel insights from four distinct research areas: systems biology, quantitative systems pharmacology, microbiology, and nutrition. BugTheDrug conceptually and technologically addresses the demand for novel approaches to the study of individual variability, thereby providing breakthrough support for progress in precision medicine.
Max ERC Funding
1 687 458 €
Duration
Start date: 2018-04-01, End date: 2023-03-31
Project acronym ODYSSEY
Project Open dynamics of interacting and disordered quantum systems
Researcher (PI) John GOOLD
Host Institution (HI) THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN
Country Ireland
Call Details Starting Grant (StG), PE3, ERC-2017-STG
Summary This research proposal focuses on the open quantum system dynamics of disordered and interacting many- body systems coupled to external baths. The dynamics of systems which contain both disorder and interactions are currently under intense theoretical investigation in condensed matter physics due to the discovery of a new phase of matter known as many-body localization. With the experimental realization of such systems in mind, this proposal addresses an essential issue which is to understand how coupling to external degrees of freedom influences dynamics. These systems are intrinsically complex and lie beyond the unitary closed system paradigm, so the research proposed here contains interdisciplinary methodology beyond the mainstream in condensed matter physics ranging from quantum information to quantum optics. The project has three principal objectives each of which would represent a major contribution to the field:
O1. To describe the dynamics of a interacting, disordered many-body systems when coupled to external baths.
O2. To perform a full characterization of spin and energy transport in their non-equilibrium steady state.
O3. To explore the system capabilities as steady state thermal machine from a systematic microscopic perspective.
This will be the first comprehensive study of the open system phenomenology of disordered interacting many-body
systems. It will also allow for the systematic study of energy and spin transport and the exploration of the potential of these systems as steady state thermal machines. In order to successfully carry out the work proposed here, the applicant will build a world class team at Trinity College Dublin. Due to his track record and interdisciplinary background in many-body physics, quantum information and statistical mechanics combined with his personal drive and ambition the applicant is in a formidable position to successfully undertake this task with the platform provided by this ERC Starting Grant.
Summary
This research proposal focuses on the open quantum system dynamics of disordered and interacting many- body systems coupled to external baths. The dynamics of systems which contain both disorder and interactions are currently under intense theoretical investigation in condensed matter physics due to the discovery of a new phase of matter known as many-body localization. With the experimental realization of such systems in mind, this proposal addresses an essential issue which is to understand how coupling to external degrees of freedom influences dynamics. These systems are intrinsically complex and lie beyond the unitary closed system paradigm, so the research proposed here contains interdisciplinary methodology beyond the mainstream in condensed matter physics ranging from quantum information to quantum optics. The project has three principal objectives each of which would represent a major contribution to the field:
O1. To describe the dynamics of a interacting, disordered many-body systems when coupled to external baths.
O2. To perform a full characterization of spin and energy transport in their non-equilibrium steady state.
O3. To explore the system capabilities as steady state thermal machine from a systematic microscopic perspective.
This will be the first comprehensive study of the open system phenomenology of disordered interacting many-body
systems. It will also allow for the systematic study of energy and spin transport and the exploration of the potential of these systems as steady state thermal machines. In order to successfully carry out the work proposed here, the applicant will build a world class team at Trinity College Dublin. Due to his track record and interdisciplinary background in many-body physics, quantum information and statistical mechanics combined with his personal drive and ambition the applicant is in a formidable position to successfully undertake this task with the platform provided by this ERC Starting Grant.
Max ERC Funding
1 333 325 €
Duration
Start date: 2018-07-01, End date: 2023-06-30
