Engineering sex-differences to improve science

This PhD project proposes an innovative exploration of how sex-specific differences in hormonal profiles and blood flow dynamics impact liver function, utilizing cutting-edge techniques involving liver organoids and microfluidic technology. Males and females differ significantly in their liver function and pathology, thought to be largely due to variations in hormonal environment and hemodynamics. Despite these observations, current approaches to elucidating these effects are limited, and rely heavily on expensive, time-consuming, and ethically challenging animal models and clinical trials. This project aims to fill this critical gap by developing and leveraging organoid-based models coupled with microfluidic systems to simulate and study the effects of these variables on liver behavior.

The overarching aims of the project will be

1. Develop and Characterize Sex-Specific Liver Organoids: Generate male and female liver organoids using cells derived from human pluripotent stem cells. These organoids will provide a 3D cellular architecture that mimics the microenvironment of the human liver.

2. Integrate Liver Organoids into a Microfluidic Platform: Deploy these organoids within a microfluidic device designed to mimic blood flow characteristics. This integration will allow for the precise control and measurement of fluid shear stress and oscillating hormone profiles, mimicking the physiological conditions of male and female circulatory systems.

3. Investigate Hormonal Impact: Examine how exposure to different levels and types of hormones, such as estrogen and testosterone, influences liver function within this controlled setting. Focus will be on key functional metrics like metabolism, bile production, and response to injury.

The project aims to reveal critical insights into the sex-specific regulatory mechanisms of liver function influenced by hormonal and hemodynamic conditions. By elucidating these differences, the research will contribute to a more nuanced understanding of liver disease pathogenesis across sexes, potentially guiding more personalized medical treatments.

Location and skills: The project will be carried out at the Institute for Bioengineering (IBioE) at the University of Edinburgh. The student will attain skills in mammalian cell culture, microfluidics, materials, optical microscopy, as well as data and image analysis.

Career development –

Institutional and Peer Support: you will benefit from an excellent supportive environment at the School of Engineering within the Institute for Bioengineering at The University of Edinburgh.

International Collaboration: the successful student will also have to opportunity visit and interact with our network of international collaborators.

Impactful publications and dissemination: the student will also benefit from strong support towards publications in world class journals and participation in major conferences as well as support to undertake outreach to the wider public.

Teaching and Research Development: the potential student will have the opportunity (once trained and familiar with relevant materials) to become a teaching assistant for courses offered at the School of Engineering.