Research Projects

Comprehensive genomic and computational model for establishment of nuclear compartments and their dependency on chromatin modifiers

German Research Center for Environmental Health

Helmholtz Zentrum München

Germany

7/13

Supervision

Maria-Elena Torres-Padilla
HMGU, 1st Supervisor

Edith Heard
*EMBL, 2nd Supervisor
*Edith Heard will move with her current lab from Institut Curie to EMBL on 01.01.2019

Objectives

Identify key molecular pathways that affect nuclear organisation and monitor the establishment of nuclear compartments in vivo, in the mouse embryo, using new imaging approaches.

Methodology

Analysis of nuclear compartments during mouse embryogenesis from the one-cell to the blastocyst stage, based on imaging and 3D-reconstruction in live embryos. The effects of over expression or RNAi of chromatin modifiers on such organisation will be tested by specific modulation of candidate pathways using the TGV method to track genomic regions. The methodology includes experimental manipulation of mouse embryos, molecular biology, genomics, live imaging and integrated image processing and modelling.

Expected Results

First analysis of live, in vivo imaging of newly formed nuclear domains in the mouse embryo. Analysis of the effect of such chromatin modifiers on chromatin openness and accessibility and their nuclear positioning, a pre-requisite for successful embryo development, and progression.

Planned Secondments

CNAG-CRG, Spain (2 x 1 month):
Modelling NGS data into comprehensive models of nuclear organisation.
Establishment of NADs and LADs after fertilisation.
MILNER THERAPEUTICS INSTITUTE, United Kingdom (1 month):
Learning drug development based on results.

Enrolment in doctoral programs

Ludwig Maximilians University of Munich (Faculty of Biology) and international PhD programme of the Helmholtz Centre in Munich (HELENA).

References

Jachowicz, J. W., Santenard, A., Bender, A., Muller, J. & Torres-Padilla, M. E. Heterochromatin establishment at pericentromeres depends on nuclear position. Genes Dev 27, 2427-2432, doi:10.1101/gad.224550.113 (2013).

Miyanari, Y., Ziegler-Birling, C. & Torres-Padilla, M. E. Live visualization of chromatin dynamics with fluorescent TALEs. Nat Struct Mol Biol 20, 1321-1324, doi:10.1038/nsmb.2680 (2013).

Borsos, M. & Torres-Padilla, M. E. Building up the nucleus: nuclear organization in the establishment of totipotency and pluripotency during mammalian development. Genes Dev 30, 611-621, doi:10.1101/gad.273805.115 (2016).