Development of a physiologically-complex model of human intestine for the study of absorption and detoxification'
Lead Research Organisation:
University of Manchester
Department Name: Physics and Astronomy
Abstract
The intestine is a primary interface between the body and external environment. It controls the uptake of nutrients (including therapeutic compounds) and acts as the first line of defence for detoxification of ingested dietary and environmental xenobiotics (toxins, mutagens, carcinogens). It is now widely accepted that as much model research as possible must be undertaken before any animal studies are considered. However, current gut model research largely relies on transwell culture based on the Caco-2 cell monolayer. This model and other similar ones lack structural and morphological complexity, making them unsuitable for studying efflux transport and metabolic enzymes expressed in the intestinal epithelium.
The aim of this PhD project is to employ a novel tissue engineering technology to generate cell sheets via a unique thermal responsive detachment process and then to construct a more physiologically-complex 3D model of the human small intestine (Lu). The functionality of cell sheets and integrated multicellular in vitro model will be assessed, followed by investigation of the regulatory pathways controlling expression of enzymes and transporters involved in nutrient digestion and absorption (Penny). The model shall also help elucidate the regulatory mechanisms which modulate expression of xenobiotic transporters and metabolic enzymes which govern cellular detoxification capacity.
The aim of this PhD project is to employ a novel tissue engineering technology to generate cell sheets via a unique thermal responsive detachment process and then to construct a more physiologically-complex 3D model of the human small intestine (Lu). The functionality of cell sheets and integrated multicellular in vitro model will be assessed, followed by investigation of the regulatory pathways controlling expression of enzymes and transporters involved in nutrient digestion and absorption (Penny). The model shall also help elucidate the regulatory mechanisms which modulate expression of xenobiotic transporters and metabolic enzymes which govern cellular detoxification capacity.
Organisations
People |
ORCID iD |
Jian Lu (Primary Supervisor) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/M011208/1 | 01/10/2015 | 31/03/2024 | |||
1707549 | Studentship | BB/M011208/1 | 01/10/2016 | 31/03/2021 |
Description | New methodologies for fabricating the classic transwell cell culture system using new materials. Understanding of the impact of substrate material on the behaviour of intestinal cells |
Exploitation Route | Impact in both pharmacy and pharmaceuticals research in academia and industry as well aspects of bio materials groups. |
Sectors | Pharmaceuticals and Medical Biotechnology |