Providing immunocompetence to human microtissue bladder models

Background

At my home lab, we established several human bladder microtissue models to understand host-uropathogen interactions in patient-like scenarios, to be tested for novel urinary tract infections (UTI) therapeutics. However, they still lack the immune cell component, which is a crucial need for the field and a main expertise of the group of Dr. Molly Ingersoll (host). In parallel, the host lab is also implementing microfluidic models to complement their routine mouse-based studies, which can be facilitated by my knowledge in tissue bioengineering. Both labs are already aware of their respective ongoing work, with frequent communication between us. Both are also working in the urinary tract infection field and familiarized with the state-of-the-art. Moreover, the conceptual idea of incorporating immune cells in the microtissue bladder models at the home lab was already shared with the Ingersoll lab. Therefore, little introduction is expected to start the experimental procedures.

Aim

University of Basel -> Institut Pasteur, Paris

The main approach that I will learn in the Ingersoll lab is the isolation, characterization, and culture of immune cells, such as monocytes, from human blood, as well as histology of tissue models. The implementation of coculturing human bladder tissue models and immune cells is envisaged in this project timeframe. Detailed description of Tasks and Outputs can be found in the Gantt chart section.

Very recently, I co-developed a unique human bladder tissue model (PMID:37939183), which allowed me to study human tissue-uropathogen interactions. However, this model still lacks the immune cell component. Having an unparalleled knowledge about inflammation and immunity in the bladder, the Ingersoll lab is the best place to learn about these processes, through histology, flow cytometry, and microscopy. The current state of the art about bladder immunity has been overlooked for decades, and the Ingersoll lab is among the few, if not the main, contributor to the field. In the context of urinary tract infection, this lab pioneered detailed analyses of several immune cells, including tissue-resident T cells and resident macrophages.

Both the isolation and characterization of immune cells, as well as their incorporation in advanced human in vitro systems are extremely novel promising approaches. This is particularly relevant regarding human bladder tissues, since only very few attempts at generating these models (without immunocompetence) are successfully reported.

As I have a basic immunology background, this knowledge transfer scheme will allow me to learn and acquire critical skills that will level up the development of human bladder tissues/organoids at my home lab. Subsequently, the data generated from the immunocompetent models will revolutionize the field not only in the UTI realm (my main area of interest), but also in modelling other bladder disorders without the use of animals.