Mechanisms of epigenetic memory by Polycomb proteins

Project Description: Epigenetic memory is central to development is also used to transmit information across generations. The Polycomb Group (PcG) proteins are key mediators of epigenetic memory. While intensive study has led to chromatin-based models of epigenetic memory, including by the PcG, we still do not have a full mechanistic understanding of how transcription states are transmitted through the disruptive events in cell division, namely DNA replication and mitosis. We are interested in the biochemical and biophysical mechanisms used by PcG proteins to “remember” transcription states. We address these questions using the simpler Drosophila system, where the PcG were discovered. Our long term goal is to reconstitute transmission of epigenetic information through DNA replication and mitosis using in vitro and cell-based assays. The current project focuses on two questions: 1) what is the role of PcG biomolecular condensates (or “PcG bodies”) in epigenetic memory through the cell cycle?; 2) what are the properties of and requirements for PcG-dependent memory? These questions stem from recent work by our team investigating how a key protein in Polycomb Repressive Complex 1 forms biomolecular condensates, and a recently established synthetic reporter-based assay for transcription memory.

Your profile

We are open to candidates with different experience, and to adapting training and projects to the student. We encourage you to apply if you have:

• A degree in biochemistry, biophysics or related discipline, or in chemistry, engineering, physics or related fields with a strong interest in learning biology (MSc level)
• A high level of motivation and curiosity
• A collaborative nature and ability to work independently and in a team

What we offer:

• A chance to work at the IRCM, a diverse internationally recognized research institute affiliated with the University of Montreal
• A chance to live in Montreal, a vibrant, cosmopolitan city with a thriving research and cultural environment
• An opportunity to work in a bilingual environment—we are a French-speaking institute, but interactions in the Francis lab occur mainly in English
• The chance to work in a lab that values diversity, technical skill, intellectual engagement, collaboration and curiosity, and is committed to scientific excellence and personal development of all members
• Our lab and our institution are committed to equity, diversity and inclusion as part of the path to excellence

About the Francis lab:

Our lab is interested in epigenetic mechanisms, with a particular focus on transcription memory and how chromatin-based information is passed through the cell cycle. Some publications relevant to this project are listed below, and more information can be found on our website https://www.francis-lab-epigenetics.ca/:

1. Gemeinhardt, T.M.^* Regy, R.M.^*, Phan, T.M.^*, Pal, N., Sharma, J., Senkovich, O., Mendiola, A.J., Ledterman, H.J., Henrickson, A., Lopes, D., Kapoor, U., Bihani, A., SIhou, D., Kim, Y.C., Jeruzalmi, D., Demeler, B., Kim, C.A., Mittal, J.^# & Francis, N.J.^# (2025) A disordered linker in the Polycomb protein Polyhomeotic tunes phase separation and oligomerization. Molecular Cell 85: 2128-2146. https://doi.org/10.1016/j.molcel.2025.05.008
2. Seif, E. Kang, J.J., Sasseville, C., Senkovich, O., Kaltashov, A., Boulier, E.L., Kapur, I., Kim, C.A., and Francis, N.J. (2020) Phase separation by the Sterile Alpha Motif of Polyhomeotic compartmentalizes Polycomb Group proteins and enhances their activity. Nat Commun 11,5609. https://rdcu.be/b9L1P
3. Alecki, C., Chiwara, V., Sanz, L. A., Grau, D., Pérez, O. A., Boulier, E. L., Armache, K.-J., Chédin, F., & Francis, N. J. (2020). RNA-DNA strand exchange by the Drosophila Polycomb complex PRC2. Nature Commun., 11(1), 1–14. https://rdcu.be/b3y5P
4. Follmer, N.E., Wani, A.H. and Francis, N.J. (2012) Polycomb Group proteins are retained at specific sites on chromatin in mitosis. PLoS Genet 8(12): e1003135. doi:10.1371/journal.pgen.1003135.
5. Lo, S.M.^*, Follmer, N.E.^*, Lengsfeld, B.M., Madamba, E.V., Seong, S., Grau, D.J., and Francis, N.J. (2012) A Bridging model for persistence of a Polycomb Group protein complex through DNA replication. Mol. Cell 46: 784-796. PMID: 22749399.
6. Francis, N.J.^#, Follmer, N.E., Simon, M.D., Aghia, G., and Butler, J.D. (2009) Polycomb proteins remain bound to chromatin and DNA during replication in vitro. Cell, 137: 110-122. PMID: 19303136.

^# corresponding author

To apply: Please send your CV and cover letter to nicole.francis@ircm.qc.ca. 3 letters of recommendation will be requested if your application is pursued.