Simmons Group: Engineering Intestinal Mesenchymal Niches to Promote Epithelial Barrier Health Through Life

Supervisor: Alison Simmons

The main focus of our lab is on understanding intestinal barrier immunity in health and disease. We are interested in how the epithelial, mesenchymal and immune cells of the intestine intersect through life to maintain a healthy dialogue with commensal microflora while protecting against enteric pathogens, preventing inflammation and cancer development, promoting healthy wound healing and enabling tissue health. We are primarily interested as to how these processes play out in humans and, as such, rely on use of the latest technical methods, advanced human tissue models and selected genetic in vivo models that recapitulate specific aspects of human intestinal biology we are studying.

The lab utilises tissue derived from extensive, meticulously curated human cohorts spanning fetal, infant to old age; inflammatory bowel disease; intestinal inflammation, pre-cancer and cancer and enteric infections. Our work is supported by leading genomic, single-cell multi-omic and subcellular spatial data resources generated in-house or via our Human Cell Atlas/Chan Zuckerberg Initiative/Helmsley Trust networks.

About the Research

Our 2025 DPhil projects include exploring in new molecular depth how intestinal fibroblasts support key structures in the intestine, such as epithelial barrier stem cells and crypt-villus units; vessel integrity and immune networks, including the establishment and dynamics of lymphoid structures in health and disease. Specifically, the DPhil will involve the use and engineering of advanced tissue models to explore the role of specific transcription factors and intercellular signalling pathways we have found to support the epithelial niche that are perturbed in inflammation, at different ages and in pre-cancer. The role of these pathways in effector function, such as in matrix biology and orchestrating stem or immune cell dynamics or effector biology, will be investigated at a functional level with a view to developing strategies to reverse fibroblast-driven pathology to promote barrier health. The MRC TIDU places a strong emphasis on innovation, and there will be opportunities for the student to engage with industry or biotech as the project develops.

This project is not suitable for part-time research. 

Training opportunities

We are a multidisciplinary lab bringing together expertise in molecular immunology, computational biology, including machine learning/AI-based approaches to data analysis, chemistry and physical science-based approaches to the study of biological problems. We are highly collaborative and facilitate utilisation or development of the latest state-of-the-art technical approaches to enable visualisation of novel biology for the first time. Our training of DPhil students incorporates technical training and support in the development of conceptual skills required to undertake truly original science at the frontiers of our current understanding.

 Examples of training opportunities linked to these studentships include:

• Organoid techniques: derivation and culture of primary human organoids, organoid/stromal/immune cell co-cultures, systematic functional perturbation of organoid cultures, high-throughput organoid screening.
• Cell biology techniques: Primary cell culture, immortalised cell culture, human cell isolation (surgical/biopsy/blood), flow cytometry.
• Genome engineering techniques: molecular cloning, viral transduction, electroporation, CRISPR/Cas9 gene editing, CRISPR activation/inference, epigenome editing.
• High-dimensional techniques: bulk RNA-seq, single-cell multiome-seq, multiplexed signalling mass cytometry.
• Next-generation sequencing (NGS) techniques: sample processing and library preparation for RNA, chromatin, protein, and DNA libraries.
• Spatial techniques: Spatial transcriptomics, immunohistochemistry, immunofluorescence, imaging mass cytometry.
• Computational techniques: Analysis of NGS data, single-cell multiomic data, spatial transcriptomics data, and mass cytometry data.

 Students will be enrolled on the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

Additional Supervisors

1. Xiao Qin 

2. Agne Antanaviciute

Publications