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Unravelling Host-Microbe-Drug interactions in Ageing and Cancer

CMCB Green Seminars

Date:15.08.2018, 11:00 - 12:00
Speaker: Filipe Cabreiro, PhD Imperial College London, Institute of Clinical Sciences, University College London, Institute of Structural and Molecular Biology
Location: CRTD Auditorium, left
Host: Dr. Maximina Yun

Abstract:

"The main interests of our lab are the molecular mechanisms underlying metabolic disease, cancer and ageing. These morbidities have a profound impact, both medically and also social and economically. Animals typically live in close association with commensal and symbiotic microbes. Recent studies have revealed that the status of gut microbiota can influence nutrition-related syndromes. However, to-date we know very little about how such interactions are regulated. The suspected role of host-microbiota interactions in human disease and regulation of metabolism is largely derived from observational studies, and it is often difficult to establish whether changes in microbiota are cause or effect of pathology. Thus, it is important to understand how these microbial communities determine human physiology, and if they can be targeted by drugs to improve human health. Our lab utilises a complementary host model organism pipeline (mice and nematode worms) with the potential to unravel drug-diet-microbe-host interactions. In particular, we utilise two tractable genetic models: the bacterium E. coli and the nematode C. elegans and combine classical and advanced microbial genetics and high-throughput genomic/chemical approaches with targeted metabolomics at the holobiont level. Our work has identified drugable mechanisms in bacteria (e.g. signalling/biochemical pathways) that alter microbial metabolite availability with the capacity to regulate host processes and physiological outputs in the context of cancer and ageing."

5 most important publications:

1 Scott, T. A., et al., Typas, A., Greene, N. D. E. & Cabreiro, F. Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy in C. elegans. Cell 169, 442-456 e418, doi:10.1016/j.cell.2017.03.040 (2017).

2 Norvaisas, P & Cabreiro F. Pharmacology in the age of the holobiont. Current opinion in systems Biology 10, 34-42, doi.org/10.1016/j.coisb.2018.05.006

3 Cabreiro, F. & Gems, D. Worms need microbes too: microbiota, health and aging in Caenorhabditis elegans. EMBO Mol Med 5, 1300-1310, doi:10.1002/emmm.201100972 (2013).

4 Cabreiro, F., et al., Greene, N. D. & Gems, D. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153, 228-239, doi:10.1016/j.cell.2013.02.035 (2013).

5 Cabreiro, F Burnett, C., Valentini, S et al., C., Partridge, L. & Gems, D. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477, 482-485, doi:10.1038/nature10296 (2011).

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