Antanaviciute Group (iCase): The GI Chronicle project: Exploring the effect of age on intestinal epithelial & immune function

Supervisor: Agne Antanaviciute

About the Research 

The effect of age, disease, and the exposome on small intestinal absorbative, metabolic, and immune function has not been well-studied. Little is understood about how the broad and complex functions of the small intestine, including digestion and the  expression/activity of digestive enzymes produced by the brush border membrane, alter, either during the human lifespan, with a range of environmental factors, or in human disease. For instance, sustained loss of intestinal brush border digestive enzyme production is well documented in patients with celiac disease, even when the disease is managed by a long-term gluten-free diet (reviewed by Bonner et al1). Yet, the extent of normal variation in brush border digestive enzyme activity across healthy individuals, and putative digestive enzyme insufficiencies in the context of diseases, food intolerances, and environmental factors, remain poorly defined. This project seeks to understand how human small intestinal function changes with age. We hypothesise that there are broad changes in digestive, absorptive, metabolic, and immunological pathways in the small intestine which occur during growth, development and aging in healthy human subjects.

By generating a richly annotated, integrated multi-omic (transcriptomics, proteomics and epigenetics) chronicle of the small intestinal epithelium across the lifespan, this DPhil project aims to establish a foundation for understanding age-associated variation in intestinal function and its relevance to health, disorders, and disease. The DPhil student will work at the interface of computational biology, gastroenterology and molecular medicine, using state-of-the-art transcriptomic, proteomic and epigenomic profiling techniques to map how intestinal epithelial and immune functions evolve across the human lifespan. This project offers an exceptional opportunity to integrate advanced bioinformatics, wet-lab and translational research within a multidisciplinary academic-industry environment. The student will gain experience in both experimental and computational methods, contributing to foundational datasets that will inform future studies on intestinal health, aging and enteropathies.

This project will be supported by Drs Mourabit and Bonner from AMYRA biosciences. The successful candidate will have the opportunity to join the Enteropathy Consortium, which brings together other AMYRA-funded/co-funded international PhD students to support innovation and collaboration.

Interested candidates are encouraged to reach out for an informal discussion (michael.fitzpatrick@ndm.ox.ac.uk and agne.antanaviciute@rdm.ox.ac.uk).

Further information about the groups’ research can be found here:

https://www.rdm.ox.ac.uk/research/antanaviciute-group-computational-biology-and-tissue-immunology

https://www.expmedndm.ox.ac.uk/tgu/research/oxford-coeliac-network

https://www.expmedndm.ox.ac.uk/team/michael-fitzpatrick

https://www.expmedndm.ox.ac.uk/tgu

Training Opportunities 

Students will have access to a wide variety of training and courses within Oxford University teaching and training schemes. As part of this project, the student will split their time between the groups of Dr. Michael FitzPatrick and Dr. Agne Antanaviciute due to interdisciplinary nature of the work. As such, the successful applicant will have access to training in the following techniques: NGS data analysis, single cell and bulk multi-omics, including scRNA-Seq, CITE-Seq, scATAC-Seq, TCR/BCR repertoire analysis, spatial ‘omics and imaging, intestinal organoids, statistical inference and machine learning. The interdisciplinary nature of this project means students will interact with and learn from experts in both wet- and dry-lab research, gaining experience in experimental design, data generation and computational data integration and modelling. In addition, opportunities will be provided for attendance at national and international workshops and conferences, as well as regularly interface with industry collaborators at AMYRA, and the opportunity to visit and collaborate with other labs within the Enteropathy Consortium.

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 

Publications