Using spatial chromatin organisation for understanding cis-regulatory logic of cellular decision-making in health and disease
Over the last decade, assays for genome-wide profiling of 3D chromatin organisation have
become essential for the study of cellular decision making in both healthy tissue and in
disease. Yet, the genomic resolution of such methods and robustness of the computational
tools for stringent analysis of such data, including identification of statistically significant
differential interactions, remains a challenge. In my presentation, I will showcase the latest
experimental approaches and computational tools that we have developed to address these
challenges. These include high-resolution miniaturised Capture Hi-C (CHi-C) for fine-scale
profiling of chromatin interactions and statistical tools for CHi-C data processing, differential
analysis and integration with other data modalities. I will then illustrate the power of these
approaches in reconstructing cis-regulatory circuits and discovering novel disease genes in
our two most recent studies. In the first, we investigated a rare type of human immune cells,
innate lymphoid Type 3 cells, and leveraged high-resolution chromatin organisation data to
reveal their role in inflammatory bowel disease. In the second, we integrated population
genetics and Capture Hi-C data to shed light on the mechanisms by which genetic variants
influence enhancer-promoter communication, with implications on gene regulation and
disease susceptibility. Finally, I will highlight how we can use these approaches as a platform
to unravel cis-regulatory circuits in rare immune and neuronal cell types in the human brain in
health and neurodegenerative disease
Date: 6 October 2023, 15:00 (Friday, 0th week, Michaelmas 2023)
Venue: IMS-Tetsuya Nakamura Building, Roosevelt Dr, Headington OX3 7TY
Venue Details: Seminar Rooms 1&2
Speaker: Prof. Valeriya Malysheva
Organisers: Dr Thomas Roberts (Department of Paediatrics), Dr Rebecca Berrens (Department of Paediatrics), Dr Filipa Simões (DPAG, IDRM, University of Oxford), Associate Professor Carlo Rinaldi (University of Oxford, MDUK Oxford Neuromuscular Centre), Dr Oliver Stone (University of Oxford, Department of Physiology, Anatomy and Genetics (DPAG))
Organiser contact email address: rufina.kaloyanova@paediatrics.ox.ac.uk
Host: Georg Hollander
Part of: IDRM Seminar Series
Booking required?: Required
Booking email: rufina.kaloyanova@paediatrics.ox.ac.uk
Audience: Members of the University only
Editor: Rufina Kaloyanova