12:00 – 12:30 Paula Hernández Calderón

Title: Functional mimicry in the human intestinal microbiome.

Abstract: The gut microbiota has gained recognition for conditioning human health and serving as the basis for the development of innovative therapeutic approaches. Nevertheless, disease causality is poorly explored, and massive association studies are strongly influenced by functional redundancy. In this study, we adopted a targeted functional metagenomics and gene-centered approach to explore the presence and impact of DPP4-like activity in the intestinal microbiota on host metabolism and health. Our hypothesis proposed is that the intestinal microbiota encodes DPP4-like activity, which could significantly influence host metabolism and overall health outcomes linked to glucose metabolism, control, satiety, and behavior. We discovered that the bacterial enzyme DPP4-like shares a similar ability to inactivate human GLP-1 and other enteroendocrine hormones and neuropeptides. Furthermore, we tested the inhibitory capacity of different gliptins, inhibitors of the human DPP4 used as pharmacological therapy in type-2 diabetes (T2D), to demonstrate their role in inhibiting the bacterial DPP4-like enzyme. Our results strongly suggest bacterial DPP4-like enzymes escape gliptin inhibition leaving an open highway to study the multiple implications this could have in the treatment and evolution of T2D. Our research line is promising to delineate either the molecular basis of metabolic dysfunction in obesity and pave the way to develop novel therapeutic approaches focused on tackling this particular microbial functional mimicry usurping control of metabolic circuits in the host.

12:30 – 13:00 Luke Noon

Title: Connecting hepatic nerves by correlative volume electron microscopy.

 Abstract: A quiet revolution is taking place in electron microscopy that will see it catapulted into the big data era and return it to the forefront of tissue biology [1,2]. Correlative light and electron microscopy (CLEM), together with volume EM (vEM) techniques, now enable us to target and investigate any cell of interest within a tissue, reconstructing large volumes of their surrounding cellular microenvironment with nanometer resolution. Advances in bigdata management and image processing are also opening up vEM datasets for computational biologists, team-based annotation, artificial intelligence and citizen science. In this talk, I will outline how, together with scientists from the UCL-LMCB (Laboratory of Molecular and Cell Biology, UK), we have developed a powerful CLEM-vEM workflow to trace peripheral nerves and identify their cellular targets in vivo. I will demonstrate how this technique can be used to map the “connectome” of peripheral nerves in liver and provide new insight into their role in regulating liver regeneration. Finally, I will outline how, together with Mario Soriano and Paco Garcia (CIPF), we are developing vEM capability for researchers in the Valencian Community by joining forces with ISABIAL (Alicante).

1. Collinson, L. M., Bosch, C., Bullen, A., Burden, J. J., Carzaniga, R., Cheng, C., Darrow, M. C., Fletcher, G., Johnson, E., Narayan, K., Peddie, C. J., Winn, M., Wood, C., Patwardhan, A., Kleywegt, G. J., & Verkade, P. (2023). Volume EM: a quiet revolution takes shape. Nature Methods, 20(6). https://doi.org/10.1038/S41592-023-01861-8
2. Eisenstein, M. (2023). Seven technologies to watch in 2023. Nature, 613(7945), 794–797. https://doi.org/10.1038/D41586-023-00178-Y