Project Description

Interactions between immune cells and the microbiome are critical for health and often become dysregulated in inflammatory bowel diseases (IBD). T cell-secreted factors regulate tissue responses to microbes and these microbes modulate immune function in a network of complex feedback mechanisms. Trans-disciplinary approaches integrating high-dimensional datasets from animal models and humans are needed to develop quantitative models of T cell-microbiome interactions. The mentoring team brings together expertise in immunology, biological data science, and mechanistic modeling to interrogate immune-microbiome interactions. The trainee would benefit from the expertise of all mentors in developing a highly trans-disciplinary skillset that they will bring to bear on developing therapeutic strategies modulating host-microbiome interactions in disease.

This project aims to understand how granzyme A (GzmA) positive T cells modulate microbiome function and how dysbiosis in turn mediates T cell function in colitis. This project will integrate data from mouse studies with multi-omics profiling of clinical samples to characterize GzmA+ T cells-microbiome interactions in IBD subtypes, specifically associations with disease severity and therapeutic resistance. These statistical models will be translated into mechanistic agent-based models to interrogate spatio-temporal properties of T cell-microbiome interactions in colitis to inform therapeutic hypotheses and better translate host-microbiome interactions across species.

Start Date

Spring/Summer 2021 

Postdoc Qualifications

The successful candidate will have expertise in one or more of the following areas: machine learning, data analytics, agent-based modeling, multi-omics data integration, systems biology, host-microbiome interaction modeling, and proficiency in one or more programming languages. 

Co-Advisors

Matthew Olson, Assistant Professor of Biological Sciences, (olson126@purdue.edu)

Elsje Pienaar, Assistant Professor of Biomedical Engineering, (epienaar@purdue.edu) 

References

Brubaker D.K., et al. “An Inter-species Translation Model Implicates Integrin Signaling in Infliximab Resistant Colonic Crohn’s Disease.” Science Signaling (2020).

Luoma, A.M., et al. “Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy.” Cell (2020).

Park, S. et al. “Granzyme A-Producing T Helper Cells are Critical for Acute Graft-Versus-Host Disease.” JCI Insight (2020).

Pienaar, E., et al. :Comparing efficacies of moxifloxacin, levofloxacin and gatifloxacin in tuberculosis granulomas using a multi-scale systems pharmacology approach” PLoS computational biology (2019)