Future Seminars
Seminar Colour Guide:
| External Faculty Speaker | |
| Faculty Seminar | Friday, 17 July 2020, 11:00Identifying gut microbiome contributions to drug metabolismMichael Zimmermann, EMBL Heidelberg, GermanyHost: Jamie HackettCNR Seminar Room, EMBL Rome Abstract: Individuals vary widely in their drug responses, which can be dangerous and expensive due to significant treatment delays and adverse effects. Growing evidence implicates the gut microbiome in this variability, however the molecular mechanisms remain mostly unknown. Using antiviral nucleoside analogues and clonazepam as examples, we recently reported experimental and computational approaches to separate host and gut microbiota contributions to drug metabolism. The resulting pharmacokinetic models identified measurable physiological, microbial and chemical parameters that dictate host and microbiome contributions to the metabolism of xenobiotics. To systematically map the drug metabolizing capacity of the gut microbiota and assess its potential contribution to drug metabolism, we further measured the ability of 76 diverse human gut bacteria to metabolize each of 271 oral drugs. We found that two thirds of these drugs are chemically modified by at least one of the tested microbes. Through combination of high-throughput bacterial genetics with mass spectrometry, we systematically identified drug-metabolizing microbial gene products. These gene products better explain the drug-metabolizing capacity of bacterial strains than their phylogenetic classification. We further demonstrate that the abundance of homologs of these gene products predict the capacity of complete human gut communities to metabolize the targeted drugs. These causal links between microbiota gene content and metabolic activities connect inter-individual microbiome variability to interpersonal differences in drug metabolism, which has translatable potential on medical therapy and drug development across multiple disease indications. |
| Faculty Seminar | |
| EMBL Distinguished Visitor Lecture | |
| EMBL - Sapienza Lecture | Friday, 2 October 2020, 11:00Epigenetics of stress allostasis: somatic mechanisms for germ cell programming of offspring developmentTracy L. Bale, Center for Epigenetic Research in Child Health and Brain Development, University of Maryland School of Medicine, USAHost: Cornelius Gross / Andrea MeleSapienza Università di Roma - Aula Odeion - Museo dell'Arte Classica - P.le Aldo Moro, 5 - Roma, EMBL Rome Abstract: Epigenetics of stress allostasis: somatic mechanisms for germ cell programming of offspring developmentTracy L. Bale, J. Chan, C. Morgan, N.A. Leu, S. Ament, B. Garcia, M. Kane, C.N. Epperson Parental lifetime exposures to perturbations such as stress, infection, malnutrition, and advanced age have been linked with an increased risk for offspring disease, including a strong association with neurodevelopmental disorders. Our studies have focused on identifying the causal biological mechanisms whereby information in the environment can be transmitted in sperm. In these studies, we demonstrate a causal role for somatic-to-germline transmission of stress information capable of altering fetal neurodevelopment via extracellular vesicles (EVs) in a preclinical model, and we further establish the translational potential of this model in a human cohort. We identified broad histone and transcriptomic alterations in mouse epididymal epithelial cells (EECs) in vivo, with corresponding persistent changes in miRNA and proteomic extracellular vesicle cargo secreted from pure caput EEC populations in vitro. In these studies, the transmission of paternal stress and changes in epigenetic marks only occur following a stress recovery period suggesting a cellular allostatic shift in chromatin programming. Using a transgenic approach, we demonstrated in vivo that the EEC glucocorticoid receptor, a central node of cellular stress mechanisms, serves a key role in this cellular programming where genetic knockdown of this receptor rescued the germline transmission of the offspring stress phenotype. We further established the causal involvement of EEC EVs utilizing intracytoplasmic sperm injection of caput sperm incubated with EVs secreted following stress treatment recovery. Translationally, we have examined similar stress programming changes in human sperm miRNA content. We utilized within and between human subject comparisons of sperm samples and neuropsychiatric perceived stress reports collected repeatedly over six months to identify a distinct miRNA expression pattern from subjects showing a post-stress recovery state. |
| Science and Society | Friday, 9 October 2020, 11:00Understanding urban environments in relation to population health Manuel Franco, University of Alcalá, Alcalá de Henares, Madrid, Spain, SpainHost: Lucia von Bredow / Cornelius GrossCNR Seminar Room, EMBL Rome Abstract: The Heart Healthy Hoods (HHH) project aimed to study the associations between the social and physical features of the urban environment and population cardiovascular health in the city of Madrid. The HHH project characterised Madrid social and physical urban environment in terms of tobacco, alcohol, food and physical activity, applying different quantitative, qualitative, GIS and participatory methodologies. The HHH team included pre-doctoral and post-doctoral researchers, co-investigators and technicians from the fields of public health, epidemiology, primary care, geography, sociology, anthropology, nursing and biology.
The HHH project has a unique and high-risk design combining urban exposure measurements with health outcomes data collected from the primary care system in the whole city of Madrid. A longitudinal cohort population-based study with 1720 participants aged 40-75 has been stablished in collaboration with over 400 primary care professionals. A follow up study of the anonymised electronic health records of 1,4 million aged 40-75 Madrid citizens who are primary care users. |
| Faculty Seminar | |
| Faculty Seminar | |
| Faculty Seminar | |
| EMBL Distinguished Visitor Lecture | |
| EMBL - Sapienza Lecture |