Research projects

This project aims to generate a new animal model to study the function of a population of Lysosome Rich Enterocytes (called LREs). Our previous results identified that the plasmolipin gene (PLLP) is necessary for the differentiation of the LREs present in a fragment of the small intestine (Ileum) that play a key and conserved role in protein absorption that is crucial for optimal nutrition and growth during development (Rodriguez-Fraticelli et al. 2015). We also found that alterations in the reciprocal interactions between host LREs, microbiota and the diet can have unexpected outcomes that aggravate nutritional deficits in malnourished individuals (Park et al, 2019). Therefore, successful probiotic interventions for environmental enteric dysfunctions (EEDs) must evaluate all aspects of these interactions in a comprehensive way.

During this last year, we observed that one of the critical regulators of intestine homeostasis is autophagy, a ubiquitous lysosomal degradative process, which the cells use to break down their material. Indeed, we found that the autophagy pathway components are highly expressed in LREs compared to IECs (Herranz et al. submitted). Indeed, we have described that during lactation, mice ileum enterocytes have very high levels of autophagy, and these are significantly reduced during the transition to weaning . And more precisely, we have seen by microscopy and flow cytometry (FACS) that these high levels of autophagy are due to an elevated autophagy flux in the LRE population.

Autophagy requires the formation of autophagosomes, a characteristic vesicular compartment formed through the hierarchical recruitment of autophagy-related (ATG) proteins. Autophagy is classified as canonical or non-canonical autophagy, differentiated by its molecular pathway and the cellular functions they regulate. Previous work has described that the amount of canonical and non-canonical autophagy are tightly regulated and determines the Autophagy Fingerprint (AF) of a tissue. Our more recent results show that epithelial cells also present a precise AF during morphogenesis (Gómez-López et al., in revision). Further, an aberrant AF resulted from defective WIPI2, ATG16L1, or Vps34 present substantial defects in lumen formation. Thus, epithelial cells' normal function requires adequate regulation of autophagy fingerprint (Gomez-Lopez et al., in revision). In the next months We aim to demonstrate the role of autophagy fingerprint in LRE function in intestine absorption and homeostasis.