Collaborations

Collaborations between RIKEN and McGill Laboratories

The McGill-RIKEN Partnership is supporting multidisciplinary collaborations in susceptibility to cancer, bioinformatic approaches for analysis of whole-genome sequence data, functional analysis of transcription factors, immunology and other areas (see the example of "Single-cell probing of epigenetic memory in immunity" below). A sample of RIKEN IMS laboratories available for collaborations are shown here and here.

If you want to propose a new collaboration, or contribute to an existing collaboration, please contact the Partnership Organising Committee by email.

Project Name

Single-cell probing of epigenetic memory in immunity

collaborators

McGill FMHS - David Langlais and Hamed S. Najafabadi
RIKEN IMS - Jay Shin and Akiko Minoda

The rapid development of sequencing-based techniques has revolutionized our comprehension of the genome(s), paving the way for gene identification, analysis of genetic diversity, determination of the epigenetic code, and study of the 3D genome structure. The recent ability to analyze the transcriptome and sites of open chromatin at single-cell resolution has highlighted the cellular heterogeneity of our organs.

From bulk experiments, we know that a limited number of transcription factors (TFs), the pioneers, can initiate the remodelling of target chromatin sites in response to developmental or stress signals. Binding to their recognition sites, the pioneer factor induces a series of events that reshapes the epigenome and the regulatory chromosomal contacts. In innate immune cells, this chromatin reprogramming initiated by a primary trigger has been recently shown to induce a stable epigenetic ‘memory’ that influences the response to further infections, a process named ‘trained immunity’. Nevertheless, due to technical limitations, it is unclear how heterogeneous is this epigenetic encryption and how individual cellular functions are affected?

The overarching objective of the project is to develop methods to overcome these technological and knowledge gaps. We aim to (1) develop bulk Single-Molecule chromatin Capture (SM-C), a method for genome-wide analysis of allele-specific interactions using single-molecule sequencing, (2) adapt it to single-cells (scSM-C) to reveal epigenetic heterogeneity, (3) develop targeted SM-C (tSM-C) by coupling chromatin-IP with single-molecule sequencing to evaluate how the recruitment of the novel pioneer factor IRF1 reprograms the transcriptional networks, and (4) share the methods and data with the community. These techniques will be a major advancement in the field of epigenetics, allowing us to understand how epigenetic diversity is established and can respond to intrinsic or extrinsic cellular needs. We will use this opportunity to investigate the molecular function of IRF1, a transcription factor well-known for its role in immune system development and its implication in autoimmune and neuroinflammatory diseases, but for which we have preliminary evidence for a role as a molecular modulator of epigenetic memory for the innate immune system.