Kennedy Trust Prize Studentships

  • Intake: UKRI-BBSRC iCASE Studentship

The liver and the intestine interact in a complex manner to maintain mutually beneficial

homeostatic functions. This cross-talk involves the modification of liver-derived factors such as
bile acids and conjugated bilirubin by the small and large intestinal microbiota, enabling
modulation of intestinal functions. Breakdown in such homeostatic functions can lead to diseases
of the liver and intestine including Primary Sclerosing Cholangitis.

In this project we aim to better understand the liver-microbiome-gut axis in health using an
interdisciplinary systems physiology approach.

The approaches undertaken will involve the analysis of high-throughput RNA-sequencing data
from both publicly available human samples (GTEx project (https://www.gtexportal.org/home/)
as well as mouse models. The project will involve analysing data derived from the liver and the
intestine in order to characterise correlated functions between these two organs. During this part
of the project you will be supervised by Dr Nicholas Ilott (Kennedy Institute of Rheumatology) to
develop skills in the development and application of bioinformatics pipelines as well as developing
an R package for the analysis of cross-tissue gene expression networks. These tools will further be
applied to answer the question of how liver-gut interactions change over the course of the
lifespan through the comparison of liver-gut co-expression networks across ages in mouse
models.

Metabolic output from the gut microbiota plays a role in mediating liver-gut interactions. As such,
you will work with Petar Scepanovic (Roche, Basel, Switzerland) over the course of 6 months to 1
year where you will integrate within BEDA (Bioinformatics Exploratory Data Analysis) team - a
group of computational biologist and biostatisticians within pRED. There you will develop
computational models that predict metabolic output from complex metagenomic data. You will
integrate these models with additional data from in vitro experimental models of bacterial
consortia to determine metabolic outputs that contribute to liver-gut cross-talk. Indeed, you will
utilise a model consortium of 12 bacterial strains in order to 1) computationally predict their
ability to metabolise liver-derived factors and 2) experimentally validate this ability using bacterial
culture techniques. Together with experienced laboratory staff at the Oxford Centre for
Microbiome Studies (OCMS), you will gain training in anaerobic and aerobic bacterial culturing
techniques and the application of such techniques to explore context-dependent metabolite
profiles. 

For full details and to apply please visit the Oxford Interdisciplinary Bioscience DTP website.